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Patient-Reported Outcomes as Independent Prognostic Factors for Survival in Oncology: Systematic Review and Meta-Analysis

Open ArchivePublished:January 06, 2021DOI:https://doi.org/10.1016/j.jval.2020.10.017

      Highlights

      • Do patient-reported outcomes (PROs) provide independent prognostic information for overall survival beyond clinical and laboratory factors typically used when making prognosis in oncology?
      • Overall, 138 studies including 158 127 patients were found. Of these, 120 (87%) studies reported at least one PRO to be statistically significantly prognostic for overall survival. Lung (n = 41, 29.7%) and genitourinary (n = 27, 19.6%) cancers were most commonly investigated.
      • There is convincing evidence that PROs provide independent prognostic information for overall survival across cancer populations and disease stages. However, further research is needed to translate current evidence-based data into prognostic tools to aid in clinical decision making.

      Abstract

      Objectives

      Assessment of patient-reported outcomes (PROs) in oncology is of critical importance because it provides unique information that may also predict clinical outcomes.

      Methods

      We conducted a systematic review of prognostic factor studies to examine the prognostic value of PROs for survival in cancer. A systematic literature search was performed in PubMed for studies published between 2013 and 2018. We considered any study, regardless of the research design, that included at least 1 PRO domain in the final multivariable prognostic model. The protocol (EPIPHANY) was published and registered in the International Prospective Register of Systematic Reviews (CRD42018099160).

      Results

      Eligibility criteria selected 138 studies including 158 127 patients, of which 43 studies were randomized, controlled trials. Overall, 120 (87%) studies reported at least 1 PRO to be statistically significantly prognostic for overall survival. Lung (n = 41, 29.7%) and genitourinary (n = 27, 19.6%) cancers were most commonly investigated. The prognostic value of PROs was investigated in secondary data analyses in 101 (73.2%) studies. The EORTC QLQ-C30 questionnaire was the most frequently used measure, and its physical functioning scale (range 0-100) the most frequent independent prognostic PRO, with a pooled hazard ratio estimate of 0.88 per 10-point increase (95% CI 0.84-0.92).

      Conclusions

      There is convincing evidence that PROs provide independent prognostic information for overall survival across cancer populations and disease stages. Further research is needed to translate current evidence-based data into prognostic tools to aid in clinical decision making.

      Keywords

      Introduction

      Patient-reported outcome (PRO) measures have historically been included in cancer clinical trials as treatment outcomes to complement information obtained via more traditional clinical and survival indicators.
      • Basch E.
      • Abernethy A.P.
      • Mullins C.D.
      • et al.
      Recommendations for incorporating patient-reported outcomes into clinical comparative effectiveness research in adult oncology.
      ,
      • Efficace F.
      • Fayers P.
      • Pusic A.
      • et al.
      Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: a pooled analysis of 557 trials.
      Their importance in the development of new cancer drugs is widely recognized by major regulatory stakeholders.
      • Kluetz P.G.
      • O’Connor D.J.
      • Soltys K.
      Incorporating the patient experience into regulatory decision making in the USA, Europe, and Canada.
      PROs also have an established application in daily routine oncology practice. There is now convincing evidence that the systematic integration of PRO assessment in the oncology clinic is associated with patient benefits such as improved symptom control, patient–physician communication, satisfaction with care, and survival outcomes.
      • Basch E.
      • Barbera L.
      • Kerrigan C.L.
      • Velikova G.
      Implementation of patient-reported outcomes in routine medical care.
      • Basch E.
      • Deal A.M.
      • Dueck A.C.
      • et al.
      Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment.
      • Basch E.
      • Deal A.M.
      • Kris M.G.
      • et al.
      Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial.
      • Denis F.
      • Lethrosne C.
      • Pourel N.
      • et al.
      Randomized trial comparing a web-mediated follow-up with routine surveillance in lung cancer patients.
      • Bennett A.V.
      • Jensen R.E.
      • Basch E.
      Electronic patient-reported outcome systems in oncology clinical practice.
      A growing body of evidence
      • Kramer J.A.
      • Curran D.
      • Piccart M.
      • et al.
      Identification and interpretation of clinical and quality of life prognostic factors for survival and response to treatment in first-line chemotherapy in advanced breast cancer.
      • Efficace F.
      • Biganzoli L.
      • Piccart M.
      • et al.
      Baseline health-related quality-of-life data as prognostic factors in a phase III multicentre study of women with metastatic breast cancer.
      • Secord A.A.
      • Coleman R.L.
      • Havrilesky L.J.
      • Abernethy A.P.
      • Samsa G.P.
      • Cella D.
      Patient-reported outcomes as end points and outcome indicators in solid tumours.
      has shown that health status information gathered through validated PRO measures provides prognostic information beyond the traditional indicators typically used in oncology, such as performance status. Three systematic reviews focused mainly on randomized, controlled trials (RCTs) have documented the independent prognostic value of PRO domains such as symptoms, global health status, and functional limitations for overall survival.
      • Gotay C.C.
      • Kawamoto C.T.
      • Bottomley A.
      • Efficace F.
      The prognostic significance of patient-reported outcomes in cancer clinical trials.
      • Montazeri A.
      Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008.
      • Mierzynska J.
      • Piccinin C.
      • Pe M.
      • et al.
      Prognostic value of patient-reported outcomes from international randomised clinical trials on cancer: a systematic review.
      Despite describing substantial heterogeneity in study design and methodological approaches for multivariable model building, these reviews
      • Gotay C.C.
      • Kawamoto C.T.
      • Bottomley A.
      • Efficace F.
      The prognostic significance of patient-reported outcomes in cancer clinical trials.
      • Montazeri A.
      Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008.
      • Mierzynska J.
      • Piccinin C.
      • Pe M.
      • et al.
      Prognostic value of patient-reported outcomes from international randomised clinical trials on cancer: a systematic review.
      all found that the EORTC QLQ-C30
      • Aaronson N.K.
      • Ahmedzai S.
      • Bergman B.
      • et al.
      The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.
      was the most frequently used questionnaire in this area. However, none of the studies identified a clear set of PRO domains that frequently emerge to predict survival in a given cancer population. Critical appraisal of how such evidence can be implemented in real-world practice has thus been limited.
      To the best of our knowledge, no state-of-the-art information is available on the amount and quality of research on the prognostic value of PROs for overall survival across all possible research designs (eg, observational studies). Such information is critical to better understand how this wealth of evidence could impact real-life practice and more accurately inform prognosis in routine cancer care.
      • Legrand C.
      • Efficace F.
      Implementing patient-reported health-related quality-of-life data in cancer routine practice to improve accuracy of prognosis: are we there yet?.
      We performed a systematic review of recently conducted studies, regardless of the research design, to investigate the value of PROs in prognostic models predicting overall survival in cancer. We also hypothesized that the EORTC QLQ-C30 was still the most frequently used PRO measure in this area. We therefore examined which PRO domains from the EORTC QLQ-C30 were most frequently included in prognostic models for overall survival.

      Materials and Methods

      Search Strategy and Selection Criteria

      The protocol for this project (EPIPHANY) was published
      • Deliu N.
      • Cottone F.
      • Collins G.S.
      • Anota A.
      • Efficace F.
      Evaluating methodological quality of prognostic models including patient-reported health outcomes in oncology (EPIPHANY): a systematic review protocol.
      and registered in the International Prospective Register of Systematic Reviews (CRD42018099160). A systematic literature search was performed in PubMed for studies published between January 2013 and February 2018. The keywords used for the PubMed search strategy can be found in Appendix 1 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.10.017.
      In accordance with the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS),
      • Moons K.G.M.
      • de Groot J.A.H.
      • Bouwmeester W.
      • et al.
      Critical appraisal and data extraction for systematic reviews of prediction modelling studies: the CHARMS checklist.
      we included prognostic model development studies with and without external data validation and studies focused solely on model validation. We included studies on adult patients with cancer (≥18 years) that predicted overall survival and included at least 1 baseline PRO as a predictor in the final multivariable prognostic model. We considered any type of study regardless of research design, including both observational studies and clinical trials (including RCTs).
      Studies were excluded when the association between baseline PROs and overall survival was examined in a univariate or unadjusted analysis only. Studies were excluded if they only considered PRO change scores over time as potential prognostic variables during model development. We only considered articles published in English and omitted literature such as reviews, commentaries, and working papers.

      Data Collection

      The data were collected electronically through the Research Electronic Data Capture platform (REDCap, Vanderbilt University; https://www.project-redcap.org/).
      • Harris P.A.
      • Taylor R.
      • Thielke R.
      • Payne J.
      • Gonzalez N.
      • Conde J.G.
      Research electronic data capture (REDCap): a metadata-driven methodology and workflow process for providing translational research informatics support.
      For each study meeting the inclusion criteria, 2 of the 6 reviewers independently extracted the information from each article. In case of discrepancies, the reviewers discussed the article to reconcile any differences until consensus was achieved. If necessary, a third senior reviewer was consulted to facilitate the reconciliation process. Each reviewer was issued a personal password to access the web database, where they completed electronic data extraction form for each article. This form collected information on study characteristics, PROs, and multivariable model development.

      Data Analysis

      Several types of information were analyzed: characteristics of the study design, cancer population, statistical methodology, number of covariates used in the prognostic model, PRO measures, and prognostic findings. For descriptive purposes, we summarized the characteristics and prognostic findings for the PROs of each eligible study separately per cancer stage. We categorized study populations as metastatic/advanced or nonmetastatic/loco-regional if at least 80% of the patients were reported as belonging to 1 of these 2 categories. If less than 80% belonged to either group or if cancer stage was not defined, we classified the study population as mixed or unclear.
      If more than one prognostic model with PROs was developed in the same study, we assessed the model with the most predictors. We classified the prognostic PRO data analysis as primary when it was reported as the original study’s primary or secondary objective. Otherwise, we classified the PRO data analysis as secondary—for example, if it involved secondary data analyses of previously conducted RCTs.
      We summarized the overall prevalence of the PRO measures used by frequencies and proportions. Based on the results, we also assessed the overall prevalence of each EORTC QLQ-C30 questionnaire scale to identify which were more frequently investigated as prognostic factors for overall survival. The QLQ-C30 physical functioning scale, which was most frequently associated with overall survival, was included in a meta-analysis to assess its prognostic influence on overall survival, including only those studies reporting continuous PRO predictors. For each study included in the meta-analysis, we reported the corresponding PRO’s hazard ratio and 95% confidence interval as per 1-point increase in the score of the scale (overall range 0-100). All hazard ratios were weighted and pooled using a random-effects model to account for the heterogeneity in the patient populations. All analyses were performed using SAS software version 9.4 (SAS Institute Inc, Cary, NC) or R software version 3.5.2.
      We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement when reporting our study.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

      Results

      Of the 1724 records screened, 138 studies including 158 127 patients with cancer met the inclusion criteria.
      • Aarstad H.J.
      • Osthus A.A.
      • Olofsson J.
      • Aarstad A.K.H.
      Level of distress predicts subsequent survival in successfully treated head and neck cancer patients: a prospective cohort study.
      • Agarwal J.P.
      • Chakraborty S.
      • Laskar S.G.
      • et al.
      Prognostic value of a patient-reported functional score versus physician-reported Karnofsky Performance Status Score in brain metastases.
      • Armstrong T.S.
      • Wefel J.S.
      • Wang M.
      • et al.
      Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma.
      • Arraras J.I.
      • Hernandez B.
      • Martinez M.
      • et al.
      Quality of life in Spanish advanced non-small-cell lung cancer patients: determinants of global QL and survival analyses.
      • Arrieta O.
      • Angulo L.P.
      • Núñez-Valencia C.
      • et al.
      Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer.
      • Baekelandt B.M.G.
      • Hjermstad M.J.
      • Nordby T.
      • et al.
      Preoperative cognitive function predicts survival in patients with resectable pancreatic ductal adenocarcinoma.
      • Bahl A.
      • Oudard S.
      • Tombal B.
      • et al.
      Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial.
      • Barata P.C.
      • Cardoso A.
      • Custodio M.P.
      • et al.
      Symptom clusters and survival in Portuguese patients with advanced cancer.
      • Barney B.J.
      • Wang X.S.
      • Lu C.
      • et al.
      Prognostic value of patient-reported symptom interference in patients with late-stage lung cancer.
      • Bascoul-Mollevi C.
      • Gourgou S.
      • Galais M.P.
      • et al.
      Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer.
      • Beer T.M.
      • Miller K.
      • Tombal B.
      • et al.
      The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: exploratory analyses of AFFIRM and PREVAIL studies.
      • Bozas G.
      • Jeffery N.
      • Ramanujam-Venkatachala D.
      • et al.
      Prognostic assessment for patients with cancer and incidental pulmonary embolism.
      • Bragstad S.
      • Flatebø M.
      • Natvig G.K.
      • et al.
      Predictors of quality of life and survival following gamma knife surgery for lung cancer brain metastases: a prospective study.
      • Brandberg Y.
      • Johansson H.
      • Aamdal S.
      • et al.
      Role functioning before start of adjuvant treatment was an independent prognostic factor for survival and time to failure: a report from the Nordic adjuvant interferon trial for patients with high-risk melanoma.
      • Braun D.P.
      • Gupta D.
      • Staren E.D.
      Longitudinal health-related quality of life assessment implications for prognosis in stage IV pancreatic cancer.
      • Brunelli A.
      • Salati M.
      • Refai M.
      • et al.
      Development of a patient-centered aggregate score to predict survival after lung resection for non-small cell lung cancer.
      • Carrillo J.F.
      • Carrillo L.C.
      • Ramirez-Ortega M.C.
      • Ochoa-Carrillo F.J.
      • Oñate-Ocaña L.F.
      The impact of treatment on quality of life of patients with head and neck cancer and its association with prognosis.
      • Cella D.
      • Traina S.
      • Li T.
      • et al.
      Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.
      • Chang Y.-L.
      • Tsai Y.-F.
      • Chao Y.-K.
      • Wu M.-Y.
      Quality-of-life measures as predictors of post-esophagectomy survival of patients with esophageal cancer.
      • Choi D.
      • Fox Z.
      • Albert T.
      • et al.
      Prediction of quality of life and survival after surgery for symptomatic spinal metastases: a multicenter cohort study to determine suitability for surgical treatment.
      • Cui J.
      • Zhou L.
      • Wee B.
      • Shen F.
      • Ma X.
      • Zhao J.
      Predicting survival time in noncurative patients with advanced cancer: a prospective study in China.
      • De Aguiar S.S.
      • Bergmann A.
      • Mattos I.E.
      Quality of life as a predictor of overall survival after breast cancer treatment.
      • Deng Y.
      • Tu H.
      • Pierzynski J.A.
      • et al.
      Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma.
      • Deschler B.
      • Ihorst G.
      • Platzbecker U.
      • et al.
      Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome.
      • Diouf M.
      • Chibaudel B.
      • Filleron T.
      • et al.
      Could baseline health-related quality of life (QoL) predict overall survival in metastatic colorectal cancer? The results of the GERCOR OPTIMOX 1 study.
      • Diouf M.
      • Filleron T.
      • Barbare J.-C.
      • et al.
      The added value of quality of life (QoL) for prognosis of overall survival in patients with palliative hepatocellular carcinoma.
      • Diouf M.
      • Filleron T.
      • Pointet A.-L.
      • et al.
      Prognostic value of health-related quality of life in patients with metastatic pancreatic adenocarcinoma: a random forest methodology.
      • Ediebah D.E.
      • Coens C.
      • Zikos E.
      • et al.
      Does change in health-related quality of life score predict survival? Analysis of EORTC 08975 lung cancer trial.
      • Efficace F.
      • Gaidano G.
      • Breccia M.
      • et al.
      Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study.
      • Eser S.
      • Göksel T.
      • Erbaycu A.E.
      • et al.
      Comparison of generic and lung cancer-specific quality of life instruments for predictive ability of survival in patients with advanced lung cancer.
      • Falandry C.
      • Weber B.
      • Savoye A.M.
      • et al.
      Development of a geriatric vulnerability score in elderly patients with advanced ovarian cancer treated with first-line carboplatin: a GINECO prospective trial.
      • Fega K.R.
      • Abel G.A.
      • Motyckova G.
      • et al.
      Non-hematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults.
      • Fiteni F.
      • Vernerey D.
      • Bonnetain F.
      • et al.
      Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients.
      • Fizazi K.
      • Massard C.
      • Smith M.
      • et al.
      Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer.
      • Fuchs C.S.
      • Muro K.
      • Tomasek J.
      • et al.
      Prognostic factor analysis of overall survival in gastric cancer from two phase III studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data.
      • Gogas H.J.
      • Karalexi M.A.
      • Dessypris N.
      • Antoniadis A.G.
      • Papadopoulos F.
      • Petridou E.T.
      The role of depression and personality traits in patients with melanoma: a South European study.
      • Goldkorn A.
      • Ely B.
      • Quinn D.I.
      • et al.
      Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer.
      • Gourgou-Bourgade S.
      • Bascoul-Mollevi C.
      • Desseigne F.
      • et al.
      Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial.
      • Gravis G.
      • Boher J.-M.
      • Fizazi K.
      • et al.
      Prognostic factors for survival in noncastrate metastatic prostate cancer: validation of the glass model and development of a novel simplified prognostic model.
      • Guo S.-S.
      • Hu W.
      • Chen Q.-Y.
      • et al.
      Pretreatment quality of life as a predictor of survival for patients with nasopharyngeal carcinoma treated with IMRT.
      • Gupta D.
      • Braun D.P.
      • Staren E.D.
      Prognostic value of changes in quality of life scores in prostate cancer.
      • Gupta D.
      • Braun D.P.
      • Staren E.D.
      • Markman M.
      Longitudinal health-related quality of life assessment: implications for prognosis in ovarian cancer.
      • Gupta D.
      • Lis C.G.
      • Rodeghier M.
      Can patient experience with service quality predict survival in colorectal cancer?.
      • Gupta D.
      • Patel K.
      • Lis C.G.
      Self-rated health supersedes patient satisfaction with service quality as a predictor of survival in prostate cancer.
      • Gupta D.
      • Rodeghier M.
      • Lis C.G.
      Patient satisfaction with service quality in an oncology setting: implications for prognosis in non-small cell lung cancer.
      • Gupta D.
      • Rodeghier M.
      • Lis C.G.
      Patient satisfaction with service quality as a predictor of survival outcomes in breast cancer.
      • Habbous S.
      • Chu K.P.
      • Harland L.T.G.
      • et al.
      Validation of a one-page patient-reported Charlson comorbidity index questionnaire for upper aerodigestive tract cancer patients.
      • Habboush Y.
      • Shannon R.P.
      • Niazi S.K.
      • et al.
      Patient-reported distress and survival among patients receiving definitive radiation therapy.
      • Hamilton B.K.
      • Law A.D.
      • Rybicki L.
      • et al.
      Prognostic significance of pre-transplant quality of life in allogeneic hematopoietic cell transplantation recipients.
      • Hernández-Socorro C.R.
      • Saavedra P.
      • Ramírez Felipe J.
      • Bohn Sarmiento U.
      • Ruiz-Santana S.
      Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.
      • Hsu T.
      • Speers C.H.
      • Kennecke H.F.
      • Cheung W.Y.
      The utility of abbreviated patient-reported outcomes for predicting survival in early stage colorectal cancer.
      • Innominato P.F.
      • Spiegel D.
      • Ulusakarya A.
      • et al.
      Subjective sleep and overall survival in chemotherapy-naïve patients with metastatic colorectal cancer.
      • Jacobs M.
      • Anderegg M.C.J.
      • Schoorlemmer A.
      • et al.
      Patients with oesophageal cancer report elevated distress and problems yet do not have an explicit wish for referral prior to receiving their medical treatment plan.
      • Kao S.C.
      • Vardy J.
      • Harvie R.
      • et al.
      Health-related quality of life and inflammatory markers in malignant pleural mesothelioma.
      • Kidane B.
      • Sulman J.
      • Xu W.
      • et al.
      Pretreatment quality-of-life score is a better discriminator of oesophageal cancer survival than performance status.
      • Kidane B.
      • Sulman J.
      • Xu W.
      • et al.
      Baseline measure of health-related quality of life (functional assessment of cancer therapy-esophagus) is associated with overall survival in patients with esophageal cancer.
      • Klaff R.
      • Varenhorst E.
      • Berglund A.
      • et al.
      Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients.
      • Klepin H.D.
      • Geiger A.M.
      • Tooze J.A.
      • et al.
      Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia.
      • Kroenke C.H.
      • Quesenberry C.
      • Kwan M.L.
      • Sweeney C.
      • Castillo A.
      • Caan B.J.
      Social networks, social support, and burden in relationships, and mortality after breast cancer diagnosis in the Life After Breast Cancer Epidemiology (LACE) study.
      • Kypriotakis G.
      • Vidrine D.J.
      • Francis L.E.
      • Rose J.H.
      The longitudinal relationship between quality of life and survival in advanced stage cancer.
      • Laird B.J.
      • Kaasa S.
      • McMillan D.C.
      • et al.
      Prognostic factors in patients with advanced cancer: a comparison of clinicopathological factors and the development of an inflammation-based prognostic system.
      • Lambert A.
      • Jarlier M.
      • Gourgou Bourgade S.
      • Conroy T.
      Response to FOLFIRINOX by gender in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial.
      • Lango M.N.
      • Egleston B.
      • Fang C.
      • et al.
      Baseline health perceptions, dysphagia, and survival in patients with head and neck cancer.
      • Lee C.K.
      • Hudson M.
      • Simes J.
      • Ribi K.
      • Bernhard J.
      • Coates A.S.
      When do patient reported quality of life indicators become prognostic in breast cancer?.
      • Lee Y.J.
      • Suh S.-Y.
      • Choi Y.S.
      • et al.
      EORTC QLQ-C15-PAL quality of life score as a prognostic indicator of survival in patients with far advanced cancer.
      • Lemonnier I.
      • Guillemin F.
      • Arveux P.
      • et al.
      Quality of life after the initial treatments of non-small-cell lung cancer: a persistent predictor for patients’ survival.
      • Li L.
      • Mo F.K.
      • Chan S.L.
      • et al.
      Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma: clinical application of health-related quality-of-life data.
      • Lis C.G.
      • Patel K.
      • Gupta D.
      The relationship between patient satisfaction with service quality and survival in non-small-cell lung cancer: is self-rated health a potential confounder?.
      • Liu Y.
      • Zhang P.-Y.
      • Na J.
      • et al.
      Prevalence, intensity, and prognostic significance of common symptoms in terminally ill cancer patients.
      • Luskin M.R.
      • Cronin A.M.
      • Owens R.L.
      • et al.
      Self-reported sleep disturbance and survival in myelodysplastic syndromes.
      • Martin A.J.
      • Gibbs E.
      • Sjoquist K.
      • et al.
      Health-related quality of life associated with regorafenib treatment in refractory advanced gastric adenocarcinoma.
      • McGee S.F.
      • Zhang T.
      • Jonker H.
      • et al.
      The impact of baseline Edmonton Symptom Assessment Scale scores on treatment and survival in patients with advanced non-small-cell lung cancer.
      • Miller K.
      • Carles J.
      • Gschwend J.E.
      • Van Poppel H.
      • Diels J.
      • Brookman-May S.D.
      The Phase 3 COU-AA-302 study of abiraterone acetate plus prednisone in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: stratified analysis based on pain, prostate-specific antigen, and Gleason score.
      • Mol L.
      • Ottevanger P.B.
      • Koopman M.
      • Punt C.J.A.
      The prognostic value of WHO performance status in relation to quality of life in advanced colorectal cancer patients.
      • Mols F.
      • Husson O.
      • Roukema J.-A.
      • van de Poll-Franse L.V.
      Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry.
      • Movsas B.
      • Hu C.
      • Sloan J.
      • et al.
      Quality of life analysis of a radiation dose-escalation study of patients with non-small-cell lung cancer: a secondary analysis of the Radiation Therapy Oncology Group 0617 randomized clinical trial.
      • Nieder C.
      • Kämpe T.A.
      • Pawinski A.
      • Dalhaug A.
      Patient-reported symptoms before palliative radiotherapy predict survival differences.
      • Noer M.C.
      • Sperling C.D.
      • Antonsen S.L.
      • Ottesen B.
      • Christensen I.J.
      • Høgdall C.
      A new clinically applicable age-specific comorbidity index for preoperative risk assessment of ovarian cancer patients.
      • Østhus A.A.
      • Aarstad A.K.H.
      • Olofsson J.
      • Aarstad H.J.
      Prediction of 5 year survival from level of perceived distress in newly diagnosed head and neck squamous cell carcinoma patients.
      • Østhus A.A.
      • Aarstad A.K.H.
      • Olofsson J.
      • Aarstad H.J.
      Prediction of survival by pretreatment health-related quality-of-life scores in a prospective cohort of patients with head and neck squamous cell carcinoma.
      • Paiva C.E.
      • Paiva B.S.R.
      Prevalence, predictors, and prognostic impact of fatigue among Brazilian outpatients with advanced cancers.
      • Palmer J.
      • Chai X.
      • Pidala J.
      • et al.
      Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease.
      • Paquette B.
      • Vernerey D.
      • Chauffert B.
      • et al.
      Prognostic value of health-related quality of life for death risk stratification in patients with unresectable glioblastoma.
      • Park S.
      • Eo W.
      • Lee S.
      The relationship between health-related quality of life and survival in metastatic colorectal cancer patients treated with Korean medicine.
      • Perrone F.
      • Jommi C.
      • Di Maio M.
      • et al.
      The association of financial difficulties with clinical outcomes in cancer patients: secondary analysis of 16 academic prospective clinical trials conducted in Italy.
      • Peters K.B.
      • West M.J.
      • Hornsby W.E.
      • et al.
      Impact of health-related quality of life and fatigue on survival of recurrent high-grade glioma patients.
      • Phippen N.T.
      • Secord A.A.
      • Wolf S.
      • et al.
      Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: an ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.
      • Pillay B.
      • Lee S.J.
      • Katona L.
      • Burney S.
      • Avery S.
      Psychosocial factors predicting survival after allogeneic stem cell transplant.
      • Pinheiro L.C.
      • Zagar T.M.
      • Reeve B.B.
      The prognostic value of pre-diagnosis health-related quality of life on survival: a prospective cohort study of older Americans with lung cancer.
      • Price M.A.
      • Butow P.N.
      • Bell M.L.
      • et al.
      Helplessness/hopelessness, minimization and optimism predict survival in women with invasive ovarian cancer: a role for targeted support during initial treatment decision-making?.
      • Quinten C.
      • Martinelli F.
      • Coens C.
      • et al.
      A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites.
      • Rees J.R.
      • Rees M.
      • McNair A.G.K.
      • et al.
      The prognostic value of patient-reported outcome data in patients with colorectal hepatic metastases who underwent surgery.
      • Reyes M.E.
      • Ye Y.
      • Zhou Y.
      • et al.
      Predictors of health-related quality of life and association with survival may identify colorectal cancer patients at high risk of poor prognosis.
      • Reyes-Gibby C.C.
      • Anderson K.O.
      • Merriman K.W.
      • Todd K.H.
      • Shete S.S.
      • Hanna E.Y.
      Survival patterns in squamous cell carcinoma of the head and neck: pain as an independent prognostic factor for survival.
      • Ringash J.
      • Fisher R.
      • Peters L.
      • et al.
      Effect of p16 status on the quality-of-life experience during chemoradiation for locally advanced oropharyngeal cancer: a substudy of randomized trial Trans-Tasman Radiation Oncology Group (TROG) 02.02 (HeadSTART).
      • Roncolato F.T.
      • Gibbs E.
      • Lee C.K.
      • et al.
      Quality of life predicts overall survival in women with platinum-resistant ovarian cancer: an AURELIA substudy.
      • Roncolato F.T.
      • Joly F.
      • O’Connell R.
      • et al.
      Reducing uncertainty: predictors of stopping chemotherapy early and shortened survival time in platinum resistant/refractory ovarian cancer—the GCIG Symptom Benefit Study.
      • Rugno F.C.
      • Paiva B.S.R.
      • Paiva C.E.
      Early integration of palliative care facilitates the discontinuation of anticancer treatment in women with advanced breast or gynecologic cancers.
      • Schild S.E.
      • Tan A.D.
      • Wampfler J.A.
      • Ross H.J.
      • Yang P.
      • Sloan J.A.
      A new scoring system for predicting survival in patients with non-small-cell lung cancer.
      • Schofield P.E.
      • Stockler M.R.
      • Zannino D.
      • et al.
      Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.
      • Schröder C.
      • Engenhart-Cabillic R.
      • Vorwerk H.
      • et al.
      Patients’ quality of life after high-dose radiation therapy for thoracic carcinomas: changes over time and influence on clinical outcome.
      • Sharma A.
      • Walker L.G.
      • Monson J.R.T.
      Baseline quality of life factors predict long term survival after elective resection for colorectal cancer.
      • Sherman A.E.
      • Motyckova G.
      • Fega K.R.
      • et al.
      Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes.
      • Shomura M.
      • Kagawa T.
      • Okabe H.
      • et al.
      Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment.
      • Singh P.S.
      • Aggarwal A.N.
      • Behera D.
      • Kapoor R.
      • Singh N.
      Simplified graded baseline symptom assessment in patients with lung cancer undergoing first-line chemotherapy: correlations and prognostic role in a resource-constrained setting.
      • Sloan J.A.
      • Cheville A.L.
      • Liu H.
      • et al.
      Impact of self-reported physical activity and health promotion behaviors on lung cancer survivorship.
      • Smyth E.N.
      • Shen W.
      • Bowman L.
      • et al.
      Patient-reported pain and other quality of life domains as prognostic factors for survival in a phase III clinical trial of patients with advanced breast cancer.
      • Spigel D.R.
      • Patel J.D.
      • Reynolds C.H.
      • et al.
      Quality of life analyses from the randomized, open-label, phase III PointBreak study of pemetrexed-carboplatin-bevacizumab followed by maintenance pemetrexed-bevacizumab versus paclitaxel-carboplatin-bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer.
      • Stauder M.C.
      • Romero Y.
      • Kabat B.
      • et al.
      Overall survival and self-reported fatigue in patients with esophageal cancer.
      • Steel J.L.
      • Geller D.A.
      • Robinson T.L.
      • et al.
      Health-related quality of life as a prognostic factor in patients with advanced cancer.
      • Stene G.B.
      • Helbostad J.L.
      • Amundsen T.
      • et al.
      Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer.
      • Sternby Eilard M.
      • Hagström H.
      • Mortensen K.E.
      • et al.
      Quality of life as a prognostic factor for survival in hepatocellular carcinoma.
      • Sugimoto H.
      • Kawashima H.
      • Ohno E.
      • et al.
      The prognostic factors and trajectory of HRQOL in patients with pancreatic cancer who received psychiatric intervention.
      • Sutradhar R.
      • Atzema C.
      • Seow H.
      • Earle C.
      • Porter J.
      • Barbera L.
      Repeated assessments of symptom severity improve predictions for risk of death among patients with cancer.
      • Tang C.
      • Hess K.
      • Bishop A.J.
      • et al.
      Creation of a prognostic index for spine metastasis to stratify survival in patients treated with spinal stereotactic radiosurgery: secondary analysis of mature prospective trials.
      • Telepak L.C.
      • Jensen S.E.
      • Dodd S.M.
      • Morgan L.S.
      • Pereira D.B.
      Psychosocial factors and mortality in women with early stage endometrial cancer.
      • Truong M.T.
      • Zhang Q.
      • Rosenthal D.I.
      • et al.
      Quality of life and performance status from a substudy conducted within a prospective phase 3 randomized trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for locally advanced head and neck carcinoma: NRG Oncology Radiation Therapy Oncology Group 0522.
      • Tsai W.-L.
      • Chien C.-Y.
      • Huang H.-Y.
      • Liao K.-C.
      • Fang F.-M.
      Prognostic value of quality of life measured after treatment on subsequent survival in patients with nasopharyngeal carcinoma.
      • Vagnildhaug O.M.
      • Blum D.
      • Wilcock A.
      • et al.
      The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis.
      • Vardy J.L.
      • Dhillon H.M.
      • Pond G.R.
      • Renton C.
      • Clarke S.J.
      • Tannock I.F.
      Prognostic indices of inflammatory markers, cognitive function and fatigue for survival in patients with localised colorectal cancer.
      • Vickers M.M.
      • Lee C.
      • Tu D.
      • et al.
      Significance of baseline and change in quality of life scores in predicting clinical outcomes in an international phase III trial of advanced pancreatic cancer: NCIC CTG PA.3.
      • Vodermaier A.
      • Linden W.
      • Rnic K.
      • et al.
      Prospective associations of depression with survival: a population-based cohort study in patients with newly diagnosed breast cancer.
      • Vodermaier A.
      • Lucas S.
      • Linden W.
      • Olson R.
      Anxiety after diagnosis predicts lung cancer-specific and overall survival in patients with stage III non-small cell lung cancer: a population-based cohort study.
      • Ward P.
      • Hecht J.R.
      • Wang H.-J.
      • et al.
      Physical function and quality of life in frail and/or elderly patients with metastatic colorectal cancer treated with capecitabine and bevacizumab: an exploratory analysis.
      • Westhoff P.G.
      • de Graeff A.
      • Monninkhof E.M.
      • et al.
      An easy tool to predict survival in patients receiving radiation therapy for painful bone metastases.
      • Wikman A.
      • Johar A.
      • Lagergren P.
      Presence of symptom clusters in surgically treated patients with esophageal cancer: implications for survival.
      • Wong C.K.H.
      • Law W.-L.
      • Wan Y.-F.
      • Poon J.T.-C.
      • Lam C.L.-K.
      Health-related quality of life and risk of colorectal cancer recurrence and all-cause death among advanced stages of colorectal cancer 1-year after diagnosis.
      • Wong E.
      • Rowbottom L.
      • Tsao M.
      • et al.
      Prognostic value of pre- and post-treatment health-related quality of life in predicting survival of patients with brain metastases.
      • Wood W.A.
      • Le-Rademacher J.
      • Syrjala K.L.
      • et al.
      Patient-reported physical functioning predicts the success of hematopoietic cell transplantation (BMT CTN 0902).
      • Woradet S.
      • Songserm N.
      • Promthet S.
      • Parkin D.M.
      Health-related quality of life and survival of cholangiocarcinoma patients in northeastern region of Thailand.
      • Wu X.
      • Ye Y.
      • Barcenas C.H.
      • et al.
      Personalized prognostic prediction models for breast cancer recurrence and survival incorporating multidimensional data.
      • Xiao C.
      • Zhang Q.
      • Nguyen-Tân P.F.
      • et al.
      Quality of life and performance status from a substudy conducted within a prospective phase 3 randomized trial of concurrent standard radiation versus accelerated radiation plus cisplatin for locally advanced head and neck carcinoma: NRG Oncology RTOG 0129.
      • Xing M.
      • Kokabi N.
      • Camacho J.C.
      • Kim H.S.
      Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization.
      • Yang C.J.
      • Roh J.-L.
      • Choi K.H.
      • et al.
      Pretreatment dysphagia inventory and videofluorographic swallowing study as prognostic indicators of early survival outcomes in head and neck cancer.
      • Yang C.J.
      • Roh J.-L.
      • Kim M.-J.
      • et al.
      Pretreatment quality of life as a prognostic factor for early survival and functional outcomes in patients with head and neck cancer.
      • Yennurajalingam S.
      • Kim Y.J.
      • Zhang Y.
      • et al.
      Factors associated with patient-reported subjective well-being among advanced lung or non-colonic gastrointestinal cancer patients.
      The identification and selection of the studies included in this review is reported in a Preferred Reporting Items for Systematic Reviews and Meta-Analysis flowchart (see Appendix 2 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.10.017). One hundred and twenty (87.0%) studies reported at least 1 PRO to be statistically significantly prognostic for overall survival in the final multivariable prognostic model.

      Overview of Study Characteristics

      Sixty-four (46.4%) studies included patients with primarily metastatic/advanced cancer, 32 (23.2%) included patients with primarily nonmetastatic/loco-regional cancer, and the remaining 42 (30.4%) included a population with mixed or unclear disease stages. Of these, 57 of 64 (89.1%) of metastatic/advanced studies, 28 of 32 (87.5%) of loco-regional/nonmetastatic studies, and 35 of 42 (83.3%) of mixed cancer population studies reported at least 1 PRO that could independently predict survival.
      Most studies (n = 94, 68.1%) had a follow-up time of more than 24 months, with a 54 % average event rate computed from 91 studies that reported this information. The prognostic value of PROs was investigated in secondary data analyses in 101 (73.2%) studies, of which 43 were retrospective analyses of RCTs. Almost all studies (n = 136, 98.6%) used the Cox proportional hazards model. Only 26 (21.7%) studies validated the final multivariable model in separate datasets or with internal validation techniques. Further details are reported in Table 1.
      Table 1Characteristics of prognostic factor studies including PROs (N = 138).
      VariableN (%)
      Significant PRO in final multivariable model
       Yes120 (87.0)
       No18 (13.0)
      Cancer stage
      When studies included metastatic and nonmetastatic patients, the study was classified as metastatic or nonmetastatic when at least 80% of the patients fell into that category.
       Primarily metastatic/advanced cancer64 (46.4)
       Primarily nonmetastatic/loco-regional cancer32 (23.2)
       Mixed/unclear cancer stage42 (30.4)
      Number of covariates considered before model building, in addition to PROs
       1-536 (26.1)
       6-829 (21.0)
       9-1232 (23.2)
       >1231 (22.5)
       Unclear10 (7.2)
      Number of patients
      Number of patients refers to those included in prognostic model development.
       <10019 (13.8)
       100-29950 (36.2)
       ≥30066 (47.8)
       Unclear3 (2.2)
      Type of PRO data analysis
      PRO data analysis was classified as primary when it was planned as the primary or secondary objective of the study. All other PRO data analyses were classified as secondary. For example, secondary data analyses of previously conducted randomized, controlled trials were considered secondary.
       Primary37 (26.8)
       Secondary101 (73.2)
      Validation of final multivariable model
      Frequencies are based on studies reporting an independent prognostic value of PROs for overall survival. Validation denotes the use of internal (eg, resampling techniques, bootstrap) or external (eg, new population setting) validation.
       Yes26 (21.7)
       No94 (78.3)
      When studies included metastatic and nonmetastatic patients, the study was classified as metastatic or nonmetastatic when at least 80% of the patients fell into that category.
      Number of patients refers to those included in prognostic model development.
      PRO data analysis was classified as primary when it was planned as the primary or secondary objective of the study. All other PRO data analyses were classified as secondary. For example, secondary data analyses of previously conducted randomized, controlled trials were considered secondary.
      § Frequencies are based on studies reporting an independent prognostic value of PROs for overall survival. Validation denotes the use of internal (eg, resampling techniques, bootstrap) or external (eg, new population setting) validation.

      Cancer Populations and Patterns of Prognostic PRO Domains

      Each of the 138 selected studies could be based on 1 or more cancer populations, assessing PROs by a single measure or by multiple measures. The most commonly investigated cancers were lung (n = 41, 29.7%), genitourinary (n = 27, 19.6%), esophagogastric (n = 25, 18.1%), and breast (n = 24, 17.4%) cancer. Figure 1 shows the 10 most frequently investigated cancers.
      Figure thumbnail gr1
      Figure 1Top 10 cancer types investigated in multivariable prognostic models with patient-reported outcomes. More than one cancer type can be present in 1 study.
      Several types of PRO domains were found to be prognostic within each cancer group. For example, more than 20 PROs were found to be independent predictors of overall survival in patients diagnosed with lung cancer.
      Performance status was found to be statistically significant in final multivariable models in 34 studies (24.6%). PROs were also statistically significant in the models of 32 (94%) of these studies.
      The full list of studies by cancer diagnosis is provided in Table 2.
      Table 2Study characteristics, measures, and results.
      First author and yearCancer typeN patients
      N refers to the number of patients included in the prognostic model development.
      Performance status statistically significant in final multivariable model
      No indicates not statistically significant in the final multivariable model for survival.
      PRO measures included in final multivariable modelPRO domain statistically significant in final multivariable model
      No indicates not statistically significant in the final multivariable model for survival.
      Brain cancer
      Armstrong et al
      • Armstrong T.S.
      • Wefel J.S.
      • Wang M.
      • et al.
      Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma.
      glioblastoma182Unclear/Not includedEORTC QLQ-C30Physical functioning, Nausea/Vomiting
      Peters et al
      • Peters K.B.
      • West M.J.
      • Hornsby W.E.
      • et al.
      Impact of health-related quality of life and fatigue on survival of recurrent high-grade glioma patients.
      including: glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma237Unclear/Not includedFACT-Br, FACIT-FFatigue
      Paquette et al
      • Paquette B.
      • Vernerey D.
      • Chauffert B.
      • et al.
      Prognostic value of health-related quality of life for death risk stratification in patients with unresectable glioblastoma.
      glioblastoma102Unclear/Not includedEORTC QLQ-BN20Future uncertainty
      Breast cancer
      Kroenke et al
      • Kroenke C.H.
      • Quesenberry C.
      • Kwan M.L.
      • Sweeney C.
      • Castillo A.
      • Caan B.J.
      Social networks, social support, and burden in relationships, and mortality after breast cancer diagnosis in the Life After Breast Cancer Epidemiology (LACE) study.
      breast2264Unclear/Not includedAd hoc patient-reported social network indexSocial network size
      De Aguiar et al
      • De Aguiar S.S.
      • Bergmann A.
      • Mattos I.E.
      Quality of life as a predictor of overall survival after breast cancer treatment.
      breast544Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-BR23Future perspective
      Gupta et al
      • Gupta D.
      • Rodeghier M.
      • Lis C.G.
      Patient satisfaction with service quality as a predictor of survival outcomes in breast cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      breast1521Unclear/Not includedService Quality QuestionnaireSingle service quality item
      Vodermaier et al
      • Vodermaier A.
      • Linden W.
      • Rnic K.
      • et al.
      Prospective associations of depression with survival: a population-based cohort study in patients with newly diagnosed breast cancer.
      breast1604Unclear/Not includedPSSCANDepression scale
      Smyth et al
      • Smyth E.N.
      • Shen W.
      • Bowman L.
      • et al.
      Patient-reported pain and other quality of life domains as prognostic factors for survival in a phase III clinical trial of patients with advanced breast cancer.
      A separate multivariable model was developed for each PRO scale.
      breast336Unclear/Not includedBPI-SF, RSCLWorst pain scale, Activity level scale
      Wu et al
      • Wu X.
      • Ye Y.
      • Barcenas C.H.
      • et al.
      Personalized prognostic prediction models for breast cancer recurrence and survival incorporating multidimensional data.
      breast5060Unclear/Not includedSF-12Physical composite score
      Lee et al
      • Lee C.K.
      • Hudson M.
      • Simes J.
      • Ribi K.
      • Bernhard J.
      • Coates A.S.
      When do patient reported quality of life indicators become prognostic in breast cancer?.
      A separate multivariable model was developed for each PRO scale.
      breast1309Unclear/Not includedLASAPhysical well-being, Appetite, Coping, Mood, Nausea/Vomiting, Utility
      Colorectal cancer
      Gupta et al
      • Gupta D.
      • Lis C.G.
      • Rodeghier M.
      Can patient experience with service quality predict survival in colorectal cancer?.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      colorectal702Unclear/Not includedService Quality QuestionnaireNo
      Sharma et al
      • Sharma A.
      • Walker L.G.
      • Monson J.R.T.
      Baseline quality of life factors predict long term survival after elective resection for colorectal cancer.
      colorectal85Unclear/Not includedFACT-C, MRSEmotional well-being, MRS score
      Diouf et al
      • Diouf M.
      • Chibaudel B.
      • Filleron T.
      • et al.
      Could baseline health-related quality of life (QoL) predict overall survival in metastatic colorectal cancer? The results of the GERCOR OPTIMOX 1 study.
      colorectal249YesEQ-5DMobility scale
      Ward et al
      • Ward P.
      • Hecht J.R.
      • Wang H.-J.
      • et al.
      Physical function and quality of life in frail and/or elderly patients with metastatic colorectal cancer treated with capecitabine and bevacizumab: an exploratory analysis.
      colorectal45NoEQ-5DNo
      Wong et al
      • Wong C.K.H.
      • Law W.-L.
      • Wan Y.-F.
      • Poon J.T.-C.
      • Lam C.L.-K.
      Health-related quality of life and risk of colorectal cancer recurrence and all-cause death among advanced stages of colorectal cancer 1-year after diagnosis.
      colorectal160Unclear/Not includedSF-12Physical functioning, General health, Vitality, Mental health
      Innominato et al
      • Innominato P.F.
      • Spiegel D.
      • Ulusakarya A.
      • et al.
      Subjective sleep and overall survival in chemotherapy-naïve patients with metastatic colorectal cancer.
      colorectal361YesEORTC QLQ-C30Insomnia
      Mol et al
      • Mol L.
      • Ottevanger P.B.
      • Koopman M.
      • Punt C.J.A.
      The prognostic value of WHO performance status in relation to quality of life in advanced colorectal cancer patients.
      colorectal555NoEORTC QLQ-C30Physical functioning
      Rees et al
      • Rees J.R.
      • Rees M.
      • McNair A.G.K.
      • et al.
      The prognostic value of patient-reported outcome data in patients with colorectal hepatic metastases who underwent surgery.
      colorectal232Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-LMC21Global health status, Constipation, Weight loss, Abdominal pain, Taste problems, Activity/Vigor problems, Sexual function
      Schofield et al
      • Schofield P.E.
      • Stockler M.R.
      • Zannino D.
      • et al.
      Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.
      colorectal407YesHADS, EQ-5DDepression, EQ-5D utility
      Hernández-Socorro et al
      • Hernández-Socorro C.R.
      • Saavedra P.
      • Ramírez Felipe J.
      • Bohn Sarmiento U.
      • Ruiz-Santana S.
      Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.
      colorectal75Unclear/Not includedSF-12SF-12 total score
      Hsu et al
      • Hsu T.
      • Speers C.H.
      • Kennecke H.F.
      • Cheung W.Y.
      The utility of abbreviated patient-reported outcomes for predicting survival in early stage colorectal cancer.
      colorectal692Unclear/Not includedPSSCANFatigue, Emotional support
      Reyes et al
      • Reyes M.E.
      • Ye Y.
      • Zhou Y.
      • et al.
      Predictors of health-related quality of life and association with survival may identify colorectal cancer patients at high risk of poor prognosis.
      A separate multivariable model was developed for each PRO scale.
      colorectal3665Unclear/Not includedSF-12Physical composite score, Mental composite score
      Park et al
      • Park S.
      • Eo W.
      • Lee S.
      The relationship between health-related quality of life and survival in metastatic colorectal cancer patients treated with Korean medicine.
      A separate multivariable model was developed for each PRO scale.
      colorectal58Unclear/Not includedFACT-GFACT-G total score, Functional well-being
      Vardy et al
      • Vardy J.L.
      • Dhillon H.M.
      • Pond G.R.
      • Renton C.
      • Clarke S.J.
      • Tannock I.F.
      Prognostic indices of inflammatory markers, cognitive function and fatigue for survival in patients with localised colorectal cancer.
      colorectal289Unclear/Not includedFACT-FNo
      Esophagogastric cancer
      Stauder et al
      • Stauder M.C.
      • Romero Y.
      • Kabat B.
      • et al.
      Overall survival and self-reported fatigue in patients with esophageal cancer.
      esophageal659Unclear/Not includedLASAFatigue
      Wikman et al
      • Wikman A.
      • Johar A.
      • Lagergren P.
      Presence of symptom clusters in surgically treated patients with esophageal cancer: implications for survival.
      A separate multivariable model was developed for each PRO scale.
      esophageal, esophagogastric junction402Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-OES18Symptom clusters: Reflux-cough, Eating difficulties
      Chang et al
      • Chang Y.-L.
      • Tsai Y.-F.
      • Chao Y.-K.
      • Wu M.-Y.
      Quality-of-life measures as predictors of post-esophagectomy survival of patients with esophageal cancer.
      esophageal67Unclear/Not includedEORTC QLQ-C30Cognitive Functioning, Dyspnea
      Kidane et al
      • Kidane B.
      • Sulman J.
      • Xu W.
      • et al.
      Baseline measure of health-related quality of life (functional assessment of cancer therapy-esophagus) is associated with overall survival in patients with esophageal cancer.
      A separate multivariable model was developed for each PRO scale.
      esophageal207Unclear/Not includedFACT-EFACT-E total score, esophageal cancer subscale
      Bascoul-Mollevi et al
      • Bascoul-Mollevi C.
      • Gourgou S.
      • Galais M.P.
      • et al.
      Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer.
      esophageal239Unclear/Not includedEORTC QLQ-OES18No
      Fuchs et al
      • Fuchs C.S.
      • Muro K.
      • Tomasek J.
      • et al.
      Prognostic factor analysis of overall survival in gastric cancer from two phase III studies of second-line ramucirumab (REGARD and RAINBOW) using pooled patient data.
      gastric, gastro-esophageal junction953YesEORTC QLQ-C30Appetite loss
      Jacobs et al
      • Jacobs M.
      • Anderegg M.C.J.
      • Schoorlemmer A.
      • et al.
      Patients with oesophageal cancer report elevated distress and problems yet do not have an explicit wish for referral prior to receiving their medical treatment plan.
      esophageal, gastro-esophageal junction187Unclear/Not includedDT/PLDaily activities, Level of distress, Constipation, Sexuality, Cluster Eating/Weight change, Cluster Fear/Tension, Cluster Fatigue/Physical ability
      Kidane et al
      • Kidane B.
      • Sulman J.
      • Xu W.
      • et al.
      Pretreatment quality-of-life score is a better discriminator of oesophageal cancer survival than performance status.
      A separate multivariable model was developed for each PRO scale.
      gastro-esophageal junction, thoracic esophagus120Unclear/Not includedFACT-EFACT-E total score, esophageal cancer subscale
      Martin et al
      • Martin A.J.
      • Gibbs E.
      • Sjoquist K.
      • et al.
      Health-related quality of life associated with regorafenib treatment in refractory advanced gastric adenocarcinoma.
      gastric adenocarcinoma (esophagogastric, stomach)136Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-STO22Physical functioning, Nausea/Vomiting, Pain, Appetite loss, Constipation, Pain (abdominal)
      Genitourinary cancer
      Bahl et al
      • Bahl A.
      • Oudard S.
      • Tombal B.
      • et al.
      Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial.
      prostate755Unclear/Not includedMPQPain
      Gupta et al
      • Gupta D.
      • Braun D.P.
      • Staren E.D.
      Prognostic value of changes in quality of life scores in prostate cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      prostate250Unclear/Not includedEORTC QLQ-C30Fatigue
      Goldkorn et al
      • Goldkorn A.
      • Ely B.
      • Quinn D.I.
      • et al.
      Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer.
      prostate212NoBPINo
      Fizazi et al
      • Fizazi K.
      • Massard C.
      • Smith M.
      • et al.
      Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer.
      prostate1901YesBPI-SFBPI-SF score
      Gravis et al
      • Gravis G.
      • Boher J.-M.
      • Fizazi K.
      • et al.
      Prognostic factors for survival in noncastrate metastatic prostate cancer: validation of the glass model and development of a novel simplified prognostic model.
      prostate385Unclear/Not includedEORTC QLQ-C30Pain
      Gupta et al
      • Gupta D.
      • Patel K.
      • Lis C.G.
      Self-rated health supersedes patient satisfaction with service quality as a predictor of survival in prostate cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      prostateUnclearUnclear/Not includedPatient Satisfaction QuestionnaireOverall self-rated health
      Klaff et al
      • Klaff R.
      • Varenhorst E.
      • Berglund A.
      • et al.
      Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      prostate900YesEORTC QLQ-C30Global health status
      Beer et al
      • Beer T.M.
      • Miller K.
      • Tombal B.
      • et al.
      The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: exploratory analyses of AFFIRM and PREVAIL studies.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      prostate1199Unclear/Not includedFACT-PFunctional well-being, Social/Family well-being score
      Beer et al
      • Beer T.M.
      • Miller K.
      • Tombal B.
      • et al.
      The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: exploratory analyses of AFFIRM and PREVAIL studies.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      prostate1717Unclear/Not includedFACT-PPhysical well-being, Emotional well-being score
      Cella et al
      • Cella D.
      • Traina S.
      • Li T.
      • et al.
      Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.
      prostate1195Unclear/Not includedBFI, FACT-PFatigue intensity, Physical well-being, Functional well-being, Prostate cancer subscale
      Cella et al
      • Cella D.
      • Traina S.
      • Li T.
      • et al.
      Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.
      prostate1088Unclear/Not includedFACT-PPhysical well-being
      Miller et al
      • Miller K.
      • Carles J.
      • Gschwend J.E.
      • Van Poppel H.
      • Diels J.
      • Brookman-May S.D.
      The Phase 3 COU-AA-302 study of abiraterone acetate plus prednisone in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: stratified analysis based on pain, prostate-specific antigen, and Gleason score.
      prostate1088NoBPI-SFBPI-SF score
      Gynecological cancer
      Gupta et al
      • Gupta D.
      • Braun D.P.
      • Staren E.D.
      • Markman M.
      Longitudinal health-related quality of life assessment: implications for prognosis in ovarian cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      ovarian137Unclear/Not includedEORTC QLQ-C30No
      Falandry et al
      • Falandry C.
      • Weber B.
      • Savoye A.M.
      • et al.
      Development of a geriatric vulnerability score in elderly patients with advanced ovarian cancer treated with first-line carboplatin: a GINECO prospective trial.
      epithelial ovarian cancer111Unclear/Not includedHADSNo
      Telepak et al
      • Telepak L.C.
      • Jensen S.E.
      • Dodd S.M.
      • Morgan L.S.
      • Pereira D.B.
      Psychosocial factors and mortality in women with early stage endometrial cancer.
      endometrial87Unclear/Not includedBrief COPEActive coping
      Noer et al
      • Noer M.C.
      • Sperling C.D.
      • Antonsen S.L.
      • Ottesen B.
      • Christensen I.J.
      • Høgdall C.
      A new clinically applicable age-specific comorbidity index for preoperative risk assessment of ovarian cancer patients.
      ovarian2020YesPatient-reported Ovarian Cancer Comorbidity IndexOvarian Cancer Comorbidity Index score
      Price et al
      • Price M.A.
      • Butow P.N.
      • Bell M.L.
      • et al.
      Helplessness/hopelessness, minimization and optimism predict survival in women with invasive ovarian cancer: a role for targeted support during initial treatment decision-making?.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      ovarian798Unclear/Not includedMACHelplessness
      Roncolato et al
      • Roncolato F.T.
      • Gibbs E.
      • Lee C.K.
      • et al.
      Quality of life predicts overall survival in women with platinum-resistant ovarian cancer: an AURELIA substudy.
      A separate multivariable model was developed for each PRO scale.
      ovarian326Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-OV28Physical functioning, Abdominal/gastrointestinal symptoms
      Phippen et al
      • Phippen N.T.
      • Secord A.A.
      • Wolf S.
      • et al.
      Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: an ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.
      epithelial ovarian cancer1152YesFACT-OFACT-O trial outcome index
      Roncolato et al
      • Roncolato F.T.
      • Joly F.
      • O’Connell R.
      • et al.
      Reducing uncertainty: predictors of stopping chemotherapy early and shortened survival time in platinum resistant/refractory ovarian cancer—the GCIG Symptom Benefit Study.
      A separate multivariable model was developed for each PRO scale.
      ovarian545Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-OV28Physical functioning, Role functioning, Global health status, Abdominal/gastrointestinal symptoms
      Head and neck cancer
      Habbous et al
      • Habbous S.
      • Chu K.P.
      • Harland L.T.G.
      • et al.
      Validation of a one-page patient-reported Charlson comorbidity index questionnaire for upper aerodigestive tract cancer patients.
      oral cavity, oropharynx, larynx, hypopharynx, nasopharynx877Unclear/Not includedPRO-CCIPRO-CCI score
      Østhus et al
      • Østhus A.A.
      • Aarstad A.K.H.
      • Olofsson J.
      • Aarstad H.J.
      Prediction of 5 year survival from level of perceived distress in newly diagnosed head and neck squamous cell carcinoma patients.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      including: laryngeal, oral cavity, oropharyngeal101Unclear/Not includedGHQ-30GHQ total score
      Østhus et al
      • Østhus A.A.
      • Aarstad A.K.H.
      • Olofsson J.
      • Aarstad H.J.
      Prediction of survival by pretreatment health-related quality-of-life scores in a prospective cohort of patients with head and neck squamous cell carcinoma.
      A separate multivariable model was developed for each PRO scale.
      including: laryngeal, oral cavity, oropharyngeal106Unclear/Not includedEORTC QLQ-C30,

      EORTC QLQ-H&N35
      Physical Functioning, Dyspnea, Insomnia, Appetite loss, Swallowing, Social eating
      Tsai et al
      • Tsai W.-L.
      • Chien C.-Y.
      • Huang H.-Y.
      • Liao K.-C.
      • Fang F.-M.
      Prognostic value of quality of life measured after treatment on subsequent survival in patients with nasopharyngeal carcinoma.
      A separate multivariable model was developed for each PRO scale.
      nasopharyngeal carcinoma273Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-H&N35Physical functioning, Fatigue, Appetite loss, Sexuality
      Aarstad et al
      • Aarstad H.J.
      • Osthus A.A.
      • Olofsson J.
      • Aarstad A.K.H.
      Level of distress predicts subsequent survival in successfully treated head and neck cancer patients: a prospective cohort study.
      including: larynx, oral cavity, oropharynx135Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-H&N35, GHQGHQ total score, Open mouth
      Lango et al
      • Lango M.N.
      • Egleston B.
      • Fang C.
      • et al.
      Baseline health perceptions, dysphagia, and survival in patients with head and neck cancer.
      including: oral cavity, oropharynx, larynx, hypopharynx, nasopharynx159NoEQ-5D-3LPain/Discomfort
      Reyes-Gibby et al
      • Reyes-Gibby C.C.
      • Anderson K.O.
      • Merriman K.W.
      • Todd K.H.
      • Shete S.S.
      • Hanna E.Y.
      Survival patterns in squamous cell carcinoma of the head and neck: pain as an independent prognostic factor for survival.
      larynx, oral cavity, pharynx2340Unclear/Not includedSF-12, ad hoc PRO item measuring painPain, Fatigue
      Yang et al
      • Yang C.J.
      • Roh J.-L.
      • Choi K.H.
      • et al.
      Pretreatment dysphagia inventory and videofluorographic swallowing study as prognostic indicators of early survival outcomes in head and neck cancer.
      A separate multivariable model was developed for each PRO scale.
      oral cavity, oropharynx, larynx, hypopharynx191Unclear/Not includedMDADIMDADI total score, Global Assessment, Emotional subscore, Functional subscore, Physical subscore
      Carrillo et al
      • Carrillo J.F.
      • Carrillo L.C.
      • Ramirez-Ortega M.C.
      • Ochoa-Carrillo F.J.
      • Oñate-Ocaña L.F.
      The impact of treatment on quality of life of patients with head and neck cancer and its association with prognosis.
      including: oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, nasal cavity, paranasal sinuses160Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-H&N35Role functioning, Pain (QLQ-H&N35), Cough
      Yang et al
      • Yang C.J.
      • Roh J.-L.
      • Kim M.-J.
      • et al.
      Pretreatment quality of life as a prognostic factor for early survival and functional outcomes in patients with head and neck cancer.
      A separate multivariable model was developed for each PRO scale.
      larynx, oral cavity, oropharynx, hypopharynx141Unclear/Not includedEORTC QLQ-C30Dyspnea, Appetite loss
      Ringash et al
      • Ringash J.
      • Fisher R.
      • Peters L.
      • et al.
      Effect of p16 status on the quality-of-life experience during chemoradiation for locally advanced oropharyngeal cancer: a substudy of randomized trial Trans-Tasman Radiation Oncology Group (TROG) 02.02 (HeadSTART).
      oropharyngeal200Unclear/Not includedFACT-H&NFACT-H&N total score
      Truong et al
      • Truong M.T.
      • Zhang Q.
      • Rosenthal D.I.
      • et al.
      Quality of life and performance status from a substudy conducted within a prospective phase 3 randomized trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for locally advanced head and neck carcinoma: NRG Oncology Radiation Therapy Oncology Group 0522.
      A separate multivariable model was developed for each PRO scale.
      oropharynx, hypopharynx, or larynx654Unclear/Not includedFACT-H&N, EQ-5D-3LFACT-G total score, FACT-H&N total score EQ-5D health index score
      Xiao et al
      • Xiao C.
      • Zhang Q.
      • Nguyen-Tân P.F.
      • et al.
      Quality of life and performance status from a substudy conducted within a prospective phase 3 randomized trial of concurrent standard radiation versus accelerated radiation plus cisplatin for locally advanced head and neck carcinoma: NRG Oncology RTOG 0129.
      A separate multivariable model was developed for each PRO scale.
      oral cavity, oropharynx, hypopharynx, or larynx646Unclear/Not includedHNRQ, SQLIHNRQ total score, SQLI total score
      Guo et al
      • Guo S.-S.
      • Hu W.
      • Chen Q.-Y.
      • et al.
      Pretreatment quality of life as a predictor of survival for patients with nasopharyngeal carcinoma treated with IMRT.
      nasopharyngeal carcinoma501Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-H&N35No
      Hematologic cancer
      Deschler et al
      • Deschler B.
      • Ihorst G.
      • Platzbecker U.
      • et al.
      Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      myelodysplastic syndromes107YesEORTC QLQ-C30Fatigue
      Klepin et al
      • Klepin H.D.
      • Geiger A.M.
      • Tooze J.A.
      • et al.
      Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia.
      acute myeloid leukemia73NoCES-D, PAT-DNo
      Sherman et al
      • Sherman A.E.
      • Motyckova G.
      • Fega K.R.
      • et al.
      Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes.
      acute myeloid leukemia101NoEORTC QLQ-C30Pain, Physical functioning (1 item each)
      Pillay et al
      • Pillay B.
      • Lee S.J.
      • Katona L.
      • Burney S.
      • Avery S.
      Psychosocial factors predicting survival after allogeneic stem cell transplant.
      AML, ALL,

      CML, CLL,

      HL, NHL, MM, MDS
      130Unclear/Not includedBSI-18Somatic scale
      Efficace et al
      • Efficace F.
      • Gaidano G.
      • Breccia M.
      • et al.
      Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study.
      myelodysplastic syndromes280NoEORTC QLQ-C30Fatigue
      Fega et al
      • Fega K.R.
      • Abel G.A.
      • Motyckova G.
      • et al.
      Non-hematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults.
      myelodysplastic syndromes114NoEORTC QLQ-C30Physical functioning (1 item)
      Hamilton et al
      • Hamilton B.K.
      • Law A.D.
      • Rybicki L.
      • et al.
      Prognostic significance of pre-transplant quality of life in allogeneic hematopoietic cell transplantation recipients.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      including: AML, MDS, myelofibrosis, CML, lymphoma, CLL409Unclear/Not includedFACT-BMTPhysical well-being
      Palmer et al
      • Palmer J.
      • Chai X.
      • Pidala J.
      • et al.
      Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease.
      including: AA, ALL, AML, CLL, CML, HL, MDS, MM, NHL308Unclear/Not includedFACT-BMTFACT-BMT total score
      Wood et al
      • Wood W.A.
      • Le-Rademacher J.
      • Syrjala K.L.
      • et al.
      Patient-reported physical functioning predicts the success of hematopoietic cell transplantation (BMT CTN 0902).
      ALL, AML, CLL, CML, MDS, MM,

      MPS, lymphoma, SLL, PCD
      646NoSF-36Physical composite score
      Luskin et al
      • Luskin M.R.
      • Cronin A.M.
      • Owens R.L.
      • et al.
      Self-reported sleep disturbance and survival in myelodysplastic syndromes.
      A separate multivariable model was developed for each PRO scale.
      myelodysplastic syndromes251Unclear/Not includedEORTC QLQ-C30Fatigue, Insomnia
      Liver cancer
      Diouf et al
      • Diouf M.
      • Filleron T.
      • Barbare J.-C.
      • et al.
      The added value of quality of life (QoL) for prognosis of overall survival in patients with palliative hepatocellular carcinoma.
      hepatocellular carcinoma215NoEORTC QLQ-C30Physical functioning
      Shomura et al
      • Shomura M.
      • Kagawa T.
      • Okabe H.
      • et al.
      Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment.
      hepatocellular carcinoma54Unclear/Not includedSF-36Physical functioning
      Woradet et al
      • Woradet S.
      • Songserm N.
      • Promthet S.
      • Parkin D.M.
      Health-related quality of life and survival of cholangiocarcinoma patients in northeastern region of Thailand.
      A separate multivariable model was developed for each PRO scale.
      cholangiocarcinoma171Unclear/Not includedFACT-HepPhysical well-being, Functional well-being, Hepatobiliary cancer subscale
      Li et al
      • Li L.
      • Mo F.K.
      • Chan S.L.
      • et al.
      Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma: clinical application of health-related quality-of-life data.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      hepatocellular carcinoma472Unclear/Not includedEORTC QLQ-C30Physical functioning, Pain, Financial difficulties
      Sternby Eilard et al
      • Sternby Eilard M.
      • Hagström H.
      • Mortensen K.E.
      • et al.
      Quality of life as a prognostic factor for survival in hepatocellular carcinoma.
      A separate multivariable model was developed for each PRO scale.
      ,
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      hepatocellular carcinoma185NoEORTC QLQ-C30, EORTC QLQ-HCC18Physical Functioning, Nutrition scale
      Xing et al
      • Xing M.
      • Kokabi N.
      • Camacho J.C.
      • Kim H.S.
      Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization.
      hepatocellular carcinoma30YesSF-36No
      Lung cancer
      Arrieta et al
      • Arrieta O.
      • Angulo L.P.
      • Núñez-Valencia C.
      • et al.
      Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer.
      non-small-cell lung cancer82Unclear/Not includedHADSDepression scale
      Barney et al
      • Barney B.J.
      • Wang X.S.
      • Lu C.
      • et al.
      Prognostic value of patient-reported symptom interference in patients with late-stage lung cancer.
      non-small-cell lung cancer90Unclear/Not includedMDASIInterference score
      Brunelli et al
      • Brunelli A.
      • Salati M.
      • Refai M.
      • et al.
      Development of a patient-centered aggregate score to predict survival after lung resection for non-small cell lung cancer.
      non-small-cell lung cancer245Unclear/Not includedSF-36Physical composite score
      Gupta et al
      • Gupta D.
      • Rodeghier M.
      • Lis C.G.
      Patient satisfaction with service quality in an oncology setting: implications for prognosis in non-small cell lung cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      non-small-cell lung cancer986Unclear/Not includedService Quality QuestionnaireNo
      Kao et al
      • Kao S.C.
      • Vardy J.
      • Harvie R.
      • et al.
      Health-related quality of life and inflammatory markers in malignant pleural mesothelioma.
      A separate multivariable model was developed for each PRO scale.
      malignant pleural mesothelioma63NoLCSSAnorexia, Fatigue, Cough, Dyspnea, Pain, Overall symptomatic distress, Interference with normal activity, global QoL, total LCSS score
      Ediebah et al
      • Ediebah D.E.
      • Coens C.
      • Zikos E.
      • et al.
      Does change in health-related quality of life score predict survival? Analysis of EORTC 08975 lung cancer trial.
      Non-small-cell lung cancer391YesEORTC QLQ-C30, EORTC QLQ-LC13Physical functioning, Pain, Dysphagia
      Lemonnier et al
      • Lemonnier I.
      • Guillemin F.
      • Arveux P.
      • et al.
      Quality of life after the initial treatments of non-small-cell lung cancer: a persistent predictor for patients’ survival.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      non-small-cell lung cancer230Unclear/Not includedEORTC QLQ-C30No
      Lis et al
      • Lis C.G.
      • Patel K.
      • Gupta D.
      The relationship between patient satisfaction with service quality and survival in non-small-cell lung cancer: is self-rated health a potential confounder?.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      non-small-cell lung cancerUnclearUnclear/Not includedPatient satisfaction questionnaireOverall self-rated health, Single patient satisfaction item
      Schild et al
      • Schild S.E.
      • Tan A.D.
      • Wampfler J.A.
      • Ross H.J.
      • Yang P.
      • Sloan J.A.
      A new scoring system for predicting survival in patients with non-small-cell lung cancer.
      non-small-cell lung cancer1274YesLCSSoverall QOL item
      Spigel et al
      • Spigel D.R.
      • Patel J.D.
      • Reynolds C.H.
      • et al.
      Quality of life analyses from the randomized, open-label, phase III PointBreak study of pemetrexed-carboplatin-bevacizumab followed by maintenance pemetrexed-bevacizumab versus paclitaxel-carboplatin-bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer.
      A separate multivariable model was developed for each PRO scale.
      Non-small-cell lung cancerUnclearYesFACT-G, FACT-L, FACT-NtxFACT-G total score, FACT-L total score, FACT-L Trial Outcome Index, FACT-Ntx total score, FACT-Ntx Trial Outcome Index
      Stene et al
      • Stene G.B.
      • Helbostad J.L.
      • Amundsen T.
      • et al.
      Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer.
      non-small-cell lung cancer35NoEORTC QLQ-C30No
      Arraras et al
      • Arraras J.I.
      • Hernandez B.
      • Martinez M.
      • et al.
      Quality of life in Spanish advanced non-small-cell lung cancer patients: determinants of global QL and survival analyses.
      A separate multivariable model was developed for each PRO scale.
      non-small-cell lung cancer39YesEORTC QLQ-C30, EORTC QLQ-LC13Physical functioning, Role functioning, Fatigue, Pain, Appetite loss, Sore mouth, Pain in arm or shoulders, Other pain sites
      Eser et al
      • Eser S.
      • Göksel T.
      • Erbaycu A.E.
      • et al.
      Comparison of generic and lung cancer-specific quality of life instruments for predictive ability of survival in patients with advanced lung cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      including: adenocarcinoma, squamous cell and small cell lung cancer299Unclear/Not includedEORTC QLQ-C30Constipation
      Fiteni et al
      • Fiteni F.
      • Vernerey D.
      • Bonnetain F.
      • et al.
      Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients.
      non-small-cell lung cancer421YesEORTC QLQ-C30Global health status
      Movsas et al
      • Movsas B.
      • Hu C.
      • Sloan J.
      • et al.
      Quality of life analysis of a radiation dose-escalation study of patients with non-small-cell lung cancer: a secondary analysis of the Radiation Therapy Oncology Group 0617 randomized clinical trial.
      A separate multivariable model was developed for each PRO scale.
      non-small-cell lung cancer302Unclear/Not includedFACT-LPhysical well-being, Functional well-being, FACT-L trial outcome index
      Singh et al
      • Singh P.S.
      • Aggarwal A.N.
      • Behera D.
      • Kapoor R.
      • Singh N.
      Simplified graded baseline symptom assessment in patients with lung cancer undergoing first-line chemotherapy: correlations and prognostic role in a resource-constrained setting.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      lung (not further specified)238YesVASFatigue
      Sloan et al
      • Sloan J.A.
      • Cheville A.L.
      • Liu H.
      • et al.
      Impact of self-reported physical activity and health promotion behaviors on lung cancer survivorship.
      lung (not further specified)1466Unclear/Not includedLCSS, Modified Baecke questionnaire for physical activityOverall QoL, Non physically active
      Agarwal et al
      • Agarwal J.P.
      • Chakraborty S.
      • Laskar S.G.
      • et al.
      Prognostic value of a patient-reported functional score versus physician-reported Karnofsky Performance Status Score in brain metastases.
      non-small-cell lung cancer140NoEORTC QLQ-C30Patient-reported functional score (derived from physical and role functional summing score)
      Pinheiro et al
      • Pinheiro L.C.
      • Zagar T.M.
      • Reeve B.B.
      The prognostic value of pre-diagnosis health-related quality of life on survival: a prospective cohort study of older Americans with lung cancer.
      A separate multivariable model was developed for each PRO scale.
      small-cell lung cancer, non-small-cell lung cancer6290Unclear/Not includedSF-36, Ad hoc PRO items measuring global HRQoLPhysical function, Role physical, Bodily pain, General health, Vitality, Social function, Role emotional, Mental health, Physical composite score, Mental composite score, Global HRQoL
      Vodermaier et al
      • Vodermaier A.
      • Lucas S.
      • Linden W.
      • Olson R.
      Anxiety after diagnosis predicts lung cancer-specific and overall survival in patients with stage III non-small cell lung cancer: a population-based cohort study.
      non-small-cell lung cancer684YesPSSCANAnxiety
      Bragstad et al
      • Bragstad S.
      • Flatebø M.
      • Natvig G.K.
      • et al.
      Predictors of quality of life and survival following gamma knife surgery for lung cancer brain metastases: a prospective study.
      non-small-cell and small cell lung cancer44Unclear/Not includedFACT-BRBrain cancer subscale
      McGee et al
      • McGee S.F.
      • Zhang T.
      • Jonker H.
      • et al.
      The impact of baseline Edmonton Symptom Assessment Scale scores on treatment and survival in patients with advanced non-small-cell lung cancer.
      non-small-cell lung cancer461YesESASNo
      Melanoma
      Brandberg et al
      • Brandberg Y.
      • Johansson H.
      • Aamdal S.
      • et al.
      Role functioning before start of adjuvant treatment was an independent prognostic factor for survival and time to failure: a report from the Nordic adjuvant interferon trial for patients with high-risk melanoma.
      melanoma785Unclear/Not includedEORTC QLQ-C30Role functioning
      Gogas et al
      • Gogas H.J.
      • Karalexi M.A.
      • Dessypris N.
      • Antoniadis A.G.
      • Papadopoulos F.
      • Petridou E.T.
      The role of depression and personality traits in patients with melanoma: a South European study.
      melanoma106Unclear/Not includedEPQLie scale
      Pancreas and bile duct
      Braun et al
      • Braun D.P.
      • Gupta D.
      • Staren E.D.
      Longitudinal health-related quality of life assessment implications for prognosis in stage IV pancreatic cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      pancreas186Unclear/Not includedEORTC QLQ-C30No
      Gourgou-Bourgade et al
      • Gourgou-Bourgade S.
      • Bascoul-Mollevi C.
      • Desseigne F.
      • et al.
      Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      pancreas320Unclear/Not includedEORTC QLQ-C30Physical functioning, Dyspnea, Constipation
      Baekelandt et al
      • Baekelandt B.M.G.
      • Hjermstad M.J.
      • Nordby T.
      • et al.
      Preoperative cognitive function predicts survival in patients with resectable pancreatic ductal adenocarcinoma.
      pancreatic ductal adenocarcinoma44Unclear/Not includedEORTC QLQ-C30Cognitive functioning
      Diouf et al
      • Diouf M.
      • Filleron T.
      • Pointet A.-L.
      • et al.
      Prognostic value of health-related quality of life in patients with metastatic pancreatic adenocarcinoma: a random forest methodology.
      pancreas98Unclear/Not includedEORTC QLQ-C30Role functioning, Insomnia
      Sugimoto et al
      • Sugimoto H.
      • Kawashima H.
      • Ohno E.
      • et al.
      The prognostic factors and trajectory of HRQOL in patients with pancreatic cancer who received psychiatric intervention.
      pancreas107YesEORTC QLQ-C30Pain
      Vickers et al
      • Vickers M.M.
      • Lee C.
      • Tu D.
      • et al.
      Significance of baseline and change in quality of life scores in predicting clinical outcomes in an international phase III trial of advanced pancreatic cancer: NCIC CTG PA.3.
      pancreas441YesEORTC QLQ-C30Physical functioning
      Lambert et al
      • Lambert A.
      • Jarlier M.
      • Gourgou Bourgade S.
      • Conroy T.
      Response to FOLFIRINOX by gender in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial.
      pancreas127Unclear/Not includedEORTC QLQ-C30Physical functioning, Dyspnea, Constipation
      Deng et al
      • Deng Y.
      • Tu H.
      • Pierzynski J.A.
      • et al.
      Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma.
      pancreatic ductal adenocarcinoma2478Unclear/Not includedSF-12Mental composite score, Physical composite score
      Mixed cancer sites
      Laird et al
      • Laird B.J.
      • Kaasa S.
      • McMillan D.C.
      • et al.
      Prognostic factors in patients with advanced cancer: a comparison of clinicopathological factors and the development of an inflammation-based prognostic system.
      including: genitourinary, breast, gynecological, gastrointestinal, head and neck, hematologic, lung1825YesEORTC QLQ-C30Dyspnea
      Liu et al
      • Liu Y.
      • Zhang P.-Y.
      • Na J.
      • et al.
      Prevalence, intensity, and prognostic significance of common symptoms in terminally ill cancer patients.
      including: urinary, breast, gynecological, gastrointestinal, head and neck, lung160YesESASFatigue, Lack of appetite, Shortness of breath
      Mols et al
      • Mols F.
      • Husson O.
      • Roukema J.-A.
      • van de Poll-Franse L.V.
      Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      endometrial, colorectal, hematologic3080Unclear/Not includedHADSDepression score
      Paiva et al
      • Paiva C.E.
      • Paiva B.S.R.
      Prevalence, predictors, and prognostic impact of fatigue among Brazilian outpatients with advanced cancers.
      urologic, breast, gynecological (n/s), colorectal, gastrointestinal, head and neck, hematologic (n/s), lung, skin, sarcomas223YesEORTC QLQ-C30Fatigue
      Cui et al
      • Cui J.
      • Zhou L.
      • Wee B.
      • Shen F.
      • Ma X.
      • Zhao J.
      Predicting survival time in noncurative patients with advanced cancer: a prospective study in China.
      unclear320YesAd hoc patient-reported symptom questionnairePain
      Lee et al
      • Lee Y.J.
      • Suh S.-Y.
      • Choi Y.S.
      • et al.
      EORTC QLQ-C15-PAL quality of life score as a prognostic indicator of survival in patients with far advanced cancer.
      A separate multivariable model was developed for each PRO scale.
      renal/bladder, ovary/cervix of uterus,

      colorectal, esophagogastric,

      head and neck, liver, lung,

      pancreas, soft tissue
      162YesEORTC QLQ-C15-PALGlobal health status, Physical functioning, Emotional functioning, Fatigue, Nausea/Vomiting, Appetite loss, Constipation
      Rugno et al
      • Rugno F.C.
      • Paiva B.S.R.
      • Paiva C.E.
      Early integration of palliative care facilitates the discontinuation of anticancer treatment in women with advanced breast or gynecologic cancers.
      gynecological, breast87YesEORTC QLQ-C30, HADSGlobal health status, Appetite loss
      Steel et al
      • Steel J.L.
      • Geller D.A.
      • Robinson T.L.
      • et al.
      Health-related quality of life as a prognostic factor in patients with advanced cancer.
      A separate multivariable model was developed for each PRO scale.
      liver, bile duct321Unclear/Not includedFACT-HepFACT-Hep total score, Physical well-being, Symptoms and side effects
      Sutradhar et al
      • Sutradhar R.
      • Atzema C.
      • Seow H.
      • Earle C.
      • Porter J.
      • Barbera L.
      Repeated assessments of symptom severity improve predictions for risk of death among patients with cancer.
      including: genitourinary, breast, colorectal, gastrointestinal, hematologic, lung66112Unclear/Not includedESASUnclear
      Westhoff et al
      • Westhoff P.G.
      • de Graeff A.
      • Monninkhof E.M.
      • et al.
      An easy tool to predict survival in patients receiving radiation therapy for painful bone metastases.
      including: genitourinary, breast, colorectal, esophageal, lung1157YesVAS, RSCLValuation of life, General Health
      Quinten et al
      • Quinten C.
      • Martinelli F.
      • Coens C.
      • et al.
      A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      genitourinary, brain, breast, colorectal, ovarian, esophageal, head and neck, lung,

      melanoma, pancreas
      7417YesEORTC QLQ-C30Physical functioning, Emotional functioning, Global health status, Nausea/Vomiting
      Choi et al
      • Choi D.
      • Fox Z.
      • Albert T.
      • et al.
      Prediction of quality of life and survival after surgery for symptomatic spinal metastases: a multicenter cohort study to determine suitability for surgical treatment.
      including: genitourinary, breast, colorectal, gastric, mixed hematologic, liver, lung, melanoma, sarcoma, thyroid922NoEQ-5DNo
      Tang et al
      • Tang C.
      • Hess K.
      • Bishop A.J.
      • et al.
      Creation of a prognostic index for spine metastasis to stratify survival in patients treated with spinal stereotactic radiosurgery: secondary analysis of mature prospective trials.
      including: renal, breast, lung, sarcoma, thyroid205YesBPIWorst pain scale
      Barata et al
      • Barata P.C.
      • Cardoso A.
      • Custodio M.P.
      • et al.
      Symptom clusters and survival in Portuguese patients with advanced cancer.
      including: genitourinary, breast, gynecological, gastrointestinal, liver, lung, pancreas and bile duct, head and neck, skin, sarcoma, central nervous system301YesESASAd hoc clinical cluster from ESAS
      Kypriotakis et al
      • Kypriotakis G.
      • Vidrine D.J.
      • Francis L.E.
      • Rose J.H.
      The longitudinal relationship between quality of life and survival in advanced stage cancer.
      Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.
      including: genitourinary, gastrointestinal, gynecological, brain, breast, head and neck, hematologic, lung, sarcoma512Unclear/Not includedFACT-GFACT-G total score
      Perrone et al
      • Perrone F.
      • Jommi C.
      • Di Maio M.
      • et al.
      The association of financial difficulties with clinical outcomes in cancer patients: secondary analysis of 16 academic prospective clinical trials conducted in Italy.
      breast, lung, ovarian3655Unclear/Not includedEORTC QLQ-C30No
      Habboush et al
      • Habboush Y.
      • Shannon R.P.
      • Niazi S.K.
      • et al.
      Patient-reported distress and survival among patients receiving definitive radiation therapy.
      including: genitourinary, brain, central nervous system, breast, gynecological, gastrointestinal, head and neck, lung, soft tissue or bone, skin, lymph node678Unclear/Not includedPRD questionnairePRD scale
      Schröder et al
      • Schröder C.
      • Engenhart-Cabillic R.
      • Vorwerk H.
      • et al.
      Patients’ quality of life after high-dose radiation therapy for thoracic carcinomas: changes over time and influence on clinical outcome.
      esophageal, lung81Unclear/Not includedEORTC QLQ-C30, EORTC QLQ-LC13No
      Vagnildhaug et al
      • Vagnildhaug O.M.
      • Blum D.
      • Wilcock A.
      • et al.
      The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis.
      including: genitourinary, breast, gynecological, esophagogastric, hematologic, lung1406YesEORTC QLQ-C15-PALPhysical functioning, Emotional functioning, Appetite loss
      Wong et al
      • Wong E.
      • Rowbottom L.
      • Tsao M.
      • et al.
      Prognostic value of pre- and post-treatment health-related quality of life in predicting survival of patients with brain metastases.
      including: genitourinary, lung, breast, gastrointestinal269YesunclearGlobal health status
      Bozas et al
      • Bozas G.
      • Jeffery N.
      • Ramanujam-Venkatachala D.
      • et al.
      Prognostic assessment for patients with cancer and incidental pulmonary embolism.
      including: breast, colorectal, esophagogastric, pancreas and bile duct, lung234YesAd hoc patient-reported symptom questionnaireNew or worsening of preexisting symptoms
      Nieder et al
      • Nieder C.
      • Kämpe T.A.
      • Pawinski A.
      • Dalhaug A.
      Patient-reported symptoms before palliative radiotherapy predict survival differences.
      genitourinary, breast, colorectal, lung, melanoma102YesESASPain, Appetite
      Yennurajalingam et al
      • Yennurajalingam S.
      • Kim Y.J.
      • Zhang Y.
      • et al.
      Factors associated with patient-reported subjective well-being among advanced lung or non-colonic gastrointestinal cancer patients.
      esophagogastric, lung, pancreas, liver826Unclear/Not includedESASPhysical distress
      BFI indicates Brief Fatigue Inventory; BPI, Brief Pain Inventory; BPI-SF, Brief Pain Inventory–Short Form; BSI-18, Brief Symptom Inventory-18; CES-D, 60-point Center for Epidemiologic Studies Depression Scale: DT/PL, Distress Thermometer and Problem List; EORTC QLQ- BN20, EORTC Quality of Life Questionnaire – Brain Tumor Module; EORTC QLQ-BR23, EORTC Quality of Life Questionnaire – Breast Cancer Module; EORTC QLQ-C30, The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30; EORTC QLQ-C15-PAL, EORTC Quality of Life Questionnaire – Palliative Care Module; EORTC QLQ-HCC18, Hepatocellular Carcinoma/Primary Liver Cancer Module; EORTC QLQ-H&N35, EORTC Quality of Life Questionnaire – Head and Neck Cancer Module; EORTC QLQ-LC13, EORTC Quality of Life Questionnaire – Lung Cancer Module; EORTC QLQ-LMC21, EORTC Quality of Life Questionnaire – Liver Metastases Colorectal Module; EORTC QLQ-OES18, EORTC Quality of Life Questionnaire – Esophageal Cancer Module; EORTC QLQ-OV28, Ovarian Cancer Module; EORTC QLQ-STO22, EORTC Quality of Life Questionnaire – Gastric Cancer Module; EPQ, Eysenck Personality Questionnaire; EQ-5D, EuroQol-5D; EQ-5D-3L, EuroQol-5D-3L; ESAS, Edmonton Symptom Assessment Scale; FACT-BMT, Functional Assessment of Cancer Therapy – Bone Marrow Transplant; FACT-BR, Functional Assessment of Cancer Therapy – Brain; FACT-C, Functional Assessment of Cancer Therapy – Colorectal; FACT-E, Functional Assessment of Cancer Therapy – Esophageal; FACIT-F, Functional Assessment of Chronic Illness Therapy – Fatigue; FACT-F, Functional Assessment of Cancer Therapy – Fatigue; FACT-G, Functional Assessment of Cancer Therapy – General; FACT/GOG-Ntx, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity Questionnaire; FACT-Hep, Functional Assessment of Cancer Therapy – Hepatobiliary; FACT-H&N, Functional Assessment of Cancer Therapy – Head and Neck Cancer; FACT-L, Functional Assessment of Cancer Therapy – Lung; FACT-P, Functional Assessment of Cancer Therapy – Prostate; FACT-O, Functional Assessment of Cancer Therapy – Ovarian Cancer; GHQ-30, General Health Questionnaire-30; HADS, Hospital Anxiety and Depression Scale; HNRQ, Head and Neck Radiotherapy Questionnaire; LASA, Linear Analog Self-Assessment; LCSS, Lung Cancer Symptom Scale; MAC, Mental Adjustment to Cancer; MDADI, MD Anderson Dysphagia Inventory; MDASI, MD Anderson Symptom Inventory; MPQ, McGill Pain Questionnaire; MRS, Mood Rating Scale; PAT-D, Pepper Assessment Tool for Disability; PRD, Patient-Reported Distress Questionnaire; PRO-CCI, Patient-Reported Carlson Comorbidity Index; PSSCAN, Psychosocial Screen for Cancer; RSCL, Rotterdam Symptom Checklist; SF-12, Short Form-12; SF-36, Short Form-36; SQLI, Spitzer Quality of Life Index; VAS, Visual Analogue Scale.
      N refers to the number of patients included in the prognostic model development.
      No indicates not statistically significant in the final multivariable model for survival.
      A separate multivariable model was developed for each PRO scale.
      § Several models were developed, with varying numbers of covariates. We considered the model with the largest number of predictors.

      PRO Measures Used in Prognostic Factor Analyses

      A wide range of PRO measures were used across in the reviewed studies. The EORTC questionnaires were the most frequently used PRO measures (n = 56, 40.6%), followed by the FACT (n = 26, 18.8%) and SF-12/36 (n = 14, 10.1%) questionnaires. Figure 2 shows the 10 most frequently used measures.
      Figure thumbnail gr2
      Figure 2Top 10 patient-reported outcome measures used in multivariable prognostic models. More than one patient-reported outcome (PRO) measure could be used in 1 study. ∗The EORTC and FACT include core and disease-specific QLQ. The SF-36 category also includes studies that used the SF-12 in the prognostic model development.
      BPI indicates Brief Pain Inventory; EORTC, European Organization for Research and Treatment of Cancer; EQ-5D, EuroQol-5D; ESAS, Edmonton Symptom Assessment System; FACT, Functional Assessment of Cancer Therapy; SF-36, Short Form Health Survey; HADS, Hospital Anxiety and Depression Scale; LCSS, Lung Cancer Symptom Scale; MDASI, MD Anderson Symptom Inventory; VAS, Visual Analogue Scale.

      Most Frequent PRO Prognostic Scales of the EORTC QLQ-C30 Questionnaire

      Of the 55 studies using the EORTC QLQ-C30 questionnaire, 41 (74.6%) reported at least 1 prognostic EORTC QLQ-C30 scale. Of these, the most frequently reported scales were physical functioning (n = 16, 39.0%), appetite loss and fatigue (each n = 7, 17.1%), and pain, dyspnea, and global quality of life/health status (each n = 6, 14.6%).
      Sixteen studies reported continuous hazard ratios for the physical functioning scale. The scale was statistically significant in 11 of these multivariable models, and the pooled hazard ratio estimate of its prognostic value was 0.88 per 10-point increase (95% confidence interval, 0.84-0.92) (Fig. 3).
      Figure thumbnail gr3
      Figure 3Association between EORTC QLQ-C30 physical functioning scale and overall survival. The forest plots represent only those 16 studies that included the physical functioning scale in the final multivariable model as a continuous variable, regardless of its statistical significance. All hazard ratios are reported as per 1-point increase in the score of the scale. ∗Statistically significant according to the p value reported by the authors in the original article.
      In studies with primarily metastatic/advanced cancer, there were 75% (6 out of 8) of multivariable models where physical functioning was statistically significant prognostic for overall survival. This proportion was also 75% (3 out of 4) in studies with primarily nonmetastatic/loco-regional cancer (details are reported in Appendix 3 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.10.017).

      Discussion

      We identified a remarkable number (N = 138) of prognostic oncology studies with PROs published in just 5 years. Around 90% of these studies found at least 1 PRO domain that predicted overall survival while controlling for key clinical and laboratory data.
      This independent association between PRO and survival was demonstrated across many cancer populations, ranging from the most common solid malignancies to rare hematologic conditions such as myelodysplastic syndromes.
      • Efficace F.
      • Gaidano G.
      • Breccia M.
      • et al.
      Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study.
      It was also consistent across different types of research, including secondary analyses of RCTs and hypothesis-driven prospective observational studies, and a wide range of PRO measures, supporting the robustness of the association. We found that PROs provided independent prognostic information for patients both with advanced/metastatic and earlier stage diseases. These findings extend previous work, which documented the independent association between PROs and survival in selected patients enrolled in clinical trials and mainly with advanced/metastatic disease.
      • Gotay C.C.
      • Kawamoto C.T.
      • Bottomley A.
      • Efficace F.
      The prognostic significance of patient-reported outcomes in cancer clinical trials.
      ,
      • Mierzynska J.
      • Piccinin C.
      • Pe M.
      • et al.
      Prognostic value of patient-reported outcomes from international randomised clinical trials on cancer: a systematic review.
      Our results are also consistent with studies in the general population. Ganna and Inglesson
      • Ganna A.
      • Ingelsson E.
      5 year mortality predictors in 498,103 UK Biobank participants: a prospective population-based study.
      conducted a population-based study on 500 000 individuals to investigate 5-year predictors of mortality. Despite the sizable amount of clinical and laboratory data considered in their analysis, which used the large UK Biobank dataset, they concluded that self-reported health was the strongest predictor of all-cause mortality in men.
      Although the mechanisms underlying the association between PROs and survival remains to be elucidated, our results provide convincing evidence that, at the very least, self-reported health status data provide unique prognostic information that is not captured with traditional clinical exams. Our findings strongly support the systematic integration of PRO data into routine practice, because PROs capture highly clinically relevant information.
      We found that the EORTC QLQ-C30 was the most frequently used PRO measure and that its physical functioning scale emerged most often as an independent prognostic factor in multivariable analyses across various cancer populations, research designs, and treatment scenarios. A recent review also reported that this scale was the most frequent prognostic PRO domain in 44 cancer RCTs published between 2006 and 2018.
      • Mierzynska J.
      • Piccinin C.
      • Pe M.
      • et al.
      Prognostic value of patient-reported outcomes from international randomised clinical trials on cancer: a systematic review.
      Wisloff and colleagues first documented the independent prognostic value of patient-reported physical functioning more than 2 decades ago,
      • Wisloff F.
      • Hjorth M.
      Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma. Nordic Myeloma Study Group.
      in newly diagnosed patients with multiple myeloma. They used a prognostic factor analysis that thoroughly considered several key disease-specific variables, such as β-2 microglobulin and extent of skeletal disease.
      • Wisloff F.
      • Hjorth M.
      Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma. Nordic Myeloma Study Group.
      Our meta-analysis estimated the magnitude of the association between patient-reported physical functioning and overall survival and found a 12% increase in the risk of death for every 10-point decrease on this scale (range 0-100). This scale is thus highly sensitive for capturing key prognostic information and can inform the design of future studies investigating the prognostic value of PROs in oncology. Physical functioning could also be considered a stratification factor in future RCTs to enhance outcome interpretation. Although performance status has traditionally been used as a key stratification variable in cancer trials,
      • Sorbye H.
      • Köhne C.H.
      • Sargent D.J.
      • Glimelius B.
      Patient characteristics and stratification in medical treatment studies for metastatic colorectal cancer: a proposal for standardization of patient characteristic reporting and stratification.
      we found that physical functioning often superseded physician-reported performance status in multivariable analyses. Although both parameters are meant to indicate physical performance, the patient’s perspective is a more sensitive parameter.
      • Mol L.
      • Ottevanger P.B.
      • Koopman M.
      • Punt C.J.A.
      The prognostic value of WHO performance status in relation to quality of life in advanced colorectal cancer patients.
      Further work is required to establish clinically relevant thresholds to effectively stratify patients in future trials.
      Our findings also emphasize the urgent need of a more rigorous and standardized approach, as well as thoughtful selection of sensitive PRO measures, to translate current evidence-based data into prognostic tools to aid in clinical decision making.
      • Legrand C.
      • Efficace F.
      Implementing patient-reported health-related quality-of-life data in cancer routine practice to improve accuracy of prognosis: are we there yet?.
      ,