Reevaluating the Evidence for Intensive Postoperative Extracolonic Surveillance for Nonmetastatic Colorectal Cancer

Published:October 12, 2021DOI:


      • A total of 3 recent trials (FACS, GILDA, and COLOFOL) failed to demonstrate a statistically significant survival advantage from intensive extracolonic surveillance for resected nonmetastatic colorectal cancer (CRC). This contrasts sharply with previous meta-analyses that found a moderate-to-large benefit from intensive follow-up. The recent evidence has been interpreted as demonstrating that extracolonic surveillance does not improve survival and, consequently, as indirect evidence that the increasingly common practice of metastasectomy may be less beneficial than previously thought.
      • This article leverages a modeling analysis to argue that the results of the trials have been misinterpreted. Given the large reduction in CRC recurrence rates over the last 30 years, the average 5-year survival benefit from intensive extracolonic surveillance would likely now be much smaller even if the benefit to patients who experience a recurrence was large. The trials were terribly underpowered to detect such a benefit. Overall, although very imprecise, the results of the 3 trials are consistent with a realistically sized survival benefit and thus should not motivate de novo skepticism about the efficacy of metastasectomy nor even risk-stratified extracolonic surveillance. Moreover, although the 5-year average benefit would be small, the predicted life-expectancy gain from the latter is comparable with CRC screening and thus would be clinically significant.
      • In the absence of experimental evidence, the true benefit of metastasectomy and consequently extracolonic surveillance remains unknown. Power analyses show that any future trial designed to compare surveillance regimens with respect to survival is practically guaranteed to be uninformative and thus would be ethically suspect. A moderate-to-large (n = 200-300) trial of salvage surgery (or of metastasectomy in particular) is needed to inform clinical practice in both cases.



      The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful.


      A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy.


      For all 3 trials, the model predicted a mortality reduction of ≤5% and power of <10%. The FACS recurrence imbalance likely led to a large relative bias (>2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P>.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance—routine computed tomography scans and carcinoembryonic antigen assays—with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients.


      Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.


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        • Bouvier A.M.
        • Launoy G.
        • Bouvier V.
        • et al.
        Incidence and patterns of late recurrences in colon cancer patients.
        Int J Cancer. 2015; 137: 2133-2138
        • Sargent D.
        • Sobrero A.
        • Grothey A.
        • et al.
        Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials.
        J Clin Oncol. 2009; 27: 872-877
        • Pickhardt P.J.
        • Edwards K.
        • Bruining D.H.
        • et al.
        Prospective trial evaluating the surgical anastomosis at one-year colorectal cancer surveillance: CT colonography versus optical colonoscopy and implications for patient care.
        Dis Colon Rectum. 2017; 60: 1162-1167
        • Kobayashi H.
        • Mochizuki H.
        • Sugihara K.
        • et al.
        Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study.
        Surgery. 2007; 141: 67-75
        • Meyerhardt J.A.
        • Mangu P.B.
        • Flynn P.J.
        • et al.
        Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement.
        J Clin Oncol. 2013; 31: 4465-4470
        • El-Shami K.
        • Oeffinger K.C.
        • Erb N.L.
        • et al.
        American Cancer Society colorectal cancer survivorship care guidelines.
        CA Cancer J Clin. 2015; 65: 428-455
        • Steele S.R.
        • Chang G.J.
        • Hendren S.
        • et al.
        Practice guideline for the surveillance of patients after curative treatment of colon and rectal cancer.
        Dis Colon Rectum. 2015; 58: 713-725
        • National Comprehensive Cancer Network
        Clinical practice guidelines in oncology: colon cancer, version 2.2015.
        (Accessed November 2015)
        • Poston G.J.
        • Tait D.
        • O’Connell S.
        • Bennett A.
        • Berendse S.
        • Guideline Development Group
        Diagnosis and management of colorectal cancer: summary of NICE guidance.
        BMJ. 2011; 343: d6751
        • Figueredo A.
        • Rumble R.B.
        • Maroun J.
        • et al.
        Follow-up of patients with curatively resected colorectal cancer: a practice guideline.
        BMC Cancer. 2003; 3: 26
        • Pita- Fernández S.
        • Alhayek- Aí M.
        • González-Martín C.
        • López-Calviño B.
        • Seoane-Pillado T.
        • Pértega-Díaz S.
        Intensive follow-up strategies improve outcomes in nonmetastatic colorectal cancer patients after curative surgery: a systematic review and meta-analysis.
        Ann Oncol. 2015; 26: 644-656
        • Renehan A.G.
        • Egger M.
        • Saunders M.P.
        • O’Dwyer S.T.
        Impact on survival of intensive follow-up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials.
        BMJ. 2002; 324: 813
        • Rosen M.
        • Chan L.
        • Beart Jr., R.W.
        • Vukasin P.
        • Anthone G.
        Follow-up of colorectal cancer: a meta-analysis.
        Dis Colon Rectum. 1998; 41: 1116-1126
        • Tjandra J.J.
        • Chan M.K.
        Follow-up after curative resection of colorectal cancer: a meta-analysis.
        Dis Colon Rectum. 2007; 50: 1783-1799
        • Jeffery M.
        • Hickey B.E.
        • Hider P.N.
        Follow-up strategies for patients treated for non-metastatic colorectal cancer.
        Cochrane Database Syst Rev. 2007; CD002200
        • Mant D.
        • Gray A.
        • Pugh S.
        • et al.
        A randomised controlled trial to assess the cost-effectiveness of intensive versus no scheduled follow-up in patients who have undergone resection for colorectal cancer with curative intent.
        Health Technol Assess. 2017; 21: 1-86
        • Primrose J.N.
        • Perera R.
        • Gray A.
        • et al.
        Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial.
        JAMA. 2014; 311: 263-270
        • Rosati G.
        • Ambrosini G.
        • Barni S.
        • et al.
        A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma.
        Ann Oncol. 2016; 27: 274-280
        • Hansdotter Andersson P.
        • Wille-Jørgensen P.
        • Horváth-Puhó E.
        • et al.
        The COLOFOL trial: study design and comparison of the study population with the source cancer population.
        Clin Epidemiol. 2016; 8: 15-21
        • Wille-Jørgensen P.
        • Syk I.
        • Smedh K.
        • et al.
        Effect of more vs less frequent follow-up testing on overall and colorectal cancer-specific mortality in patients with stage II or III colorectal cancer: the COLOFOL randomized clinical trial.
        JAMA. 2018; 319: 2095-2103
        • Jeffery M.
        • Hickey B.E.
        • Hider P.N.
        Follow-up strategies for patients treated for non-metastatic colorectal cancer.
        Cochrane Database Syst Rev. 2019; 9CD002200
        • Mokhles S.
        • Macbeth F.
        • Farewell V.
        • et al.
        Meta-analysis of colorectal cancer follow-up after potentially curative resection.
        Br J Surg. 2016; 103: 1259-1268
        • Jeffery M.
        • Hickey B.E.
        • Hider P.N.
        See AM. Follow-up strategies for patients treated for non-metastatic colorectal cancer.
        Cochrane Database Syst Rev. 2016; 11CD002200
        • Synder R.A.
        • Chang G.J.
        Surveillance testing for colorectal cancer: new evidence supports a change in guidelines. Bulletin of the American College of Surgeons.
        (Accessed June 1, 2019)
        • Holme Ø.
        • Bretthauer M.
        • Løberg M.
        • Kalager M.
        • Adami H.O.
        Revisiting surveillance schemes for cancer survivors.
        Ann Oncol. 2019; 30: 881-883
        • Asensio Martínez E.
        • Gómez González L.
        • Morales Giménez R.
        • Pelegrín Mateo F.J.
        • Fernández Cruz M.
        • Gallego Plazas J.
        Is it time to change follow-up recommendations in colorectal cancer?.
        Clin Transl Oncol. 2020; 22: 163-164
        • Pal S.K.
        • Miller M.J.
        • Agarwal N.
        • et al.
        Clinical cancer Advances 2019: annual report on progress against cancer from the American Society of Clinical Oncology.
        J Clin Oncol. 2019; 37: 834-849
        • Treasure T.
        • Farewell V.
        • Macbeth F.
        • et al.
        Pulmonary Metastasectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial.
        Trials. 2019; 20: 718
        • Treasure T.
        • Russell C.
        • Macbeth F.
        Re-launch of PulMiCC trial to discover the true effect of pulmonary metastasectomy on survival in advanced colorectal cancer.
        BMJ. 2015; 351: h6045
        • Treasure T.
        Questioning the benefit of lung metastasectomy in colorectal cancer.
        BMJ. 2020; 368: m264
        • Milosevic M.
        • Edwards J.
        • Tsang D.
        • et al.
        Pulmonary metastasectomy in colorectal cancer: updated analysis of 93 randomised patients-control survival is much better than previously assumed.
        Colorectal Dis. 2020; 22: 1314-1324
        • Bartlett E.K.
        • Simmons K.D.
        • Wachtel H.
        • et al.
        The rise in metastasectomy across cancer types over the past decade.
        Cancer. 2015; 121: 747-757
        • Sanoff H.K.
        Best evidence supports annual surveillance for resected colorectal cancer.
        JAMA. 2018; 319: 2083-2085
        • Snyder R.A.
        • Hu C.Y.
        • Cuddy A.
        • et al.
        Association between intensity of posttreatment surveillance testing and detection of recurrence in patients with colorectal cancer.
        JAMA. 2018; 319: 2104-2115
        • Liu S.L.
        • Cheung W.Y.
        Role of surveillance imaging and endoscopy in colorectal cancer follow-up: quality over quantity?.
        World J Gastroenterol. 2019; 25: 59-68
        • Snyder R.A.
        • Chang G.J.
        Surveillance testing for colorectal cancer: new evidence supports a change in guidelines.
        (Accessed May 31, 2019)
      1. R Core Team. R: A Language and Environment for Statistical Computing [computer program]. Vienna, Austria: R Foundation for Statistical Computing; 2013.

        • Sargent D.J.
        • Patiyil S.
        • Yothers G.
        • et al.
        End points for colon cancer adjuvant trials: observations and recommendations based on individual patient data from 20,898 patients enrolled onto 18 randomized trials from the ACCENT Group.
        J Clin Oncol. 2007; 25: 4569-4574
        • Shah M.A.
        • Renfro L.A.
        • Allegra C.J.
        • et al.
        Impact of patient factors on recurrence risk and time dependency of oxaliplatin benefit in patients with colon cancer: analysis from modern-era adjuvant studies in the adjuvant colon cancer end points (ACCENT) database.
        J Clin Oncol. 2016; 34: 843-853
        • Shi Q.
        • Andre T.
        • Grothey A.
        • et al.
        Comparison of outcomes after fluorouracil-based adjuvant therapy for stages II and III colon cancer between 1978 to 1995 and 1996 to 2007: evidence of stage migration from the ACCENT database.
        J Clin Oncol. 2013; 31: 3656-3663
        • Teloken P.E.
        • Ransom D.
        • Faragher I.
        • Jones I.
        • Gibbs P.
        • Platell C.
        Recurrence in patients with stage I colorectal cancer.
        ANZ J Surg. 2016; 86: 49-53
        • van Gijn W.
        • Marijnen C.A.
        • Nagtegaal I.D.
        • et al.
        Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial.
        Lancet Oncol. 2011; 12: 575-582
        • Gray R.
        • Barnwell J.
        • et al.
        • Quasar Collaborative Group
        Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.
        Lancet. 2007; 370: 2020-2029
        • Rödel C.
        • Graeven U.
        • Fietkau R.
        • et al.
        Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial.
        Lancet Oncol. 2015; 16: 979-989
        • Finlay I.G.
        • Meek D.
        • Brunton F.
        • McArdle C.S.
        Growth rate of hepatic metastases in colorectal carcinoma.
        Br J Surg. 1988; 75: 641-644
        • Ichikawa T.
        • Saito K.
        • Yoshioka N.
        • et al.
        Detection and characterization of focal liver lesions: a Japanese phase III, multicenter comparison between gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced computed tomography predominantly in patients with hepatocellular carcinoma and chronic liver disease.
        Invest Radiol. 2010; 45: 133-141
        • Niekel M.C.
        • Bipat S.
        • Stoker J.
        Diagnostic imaging of colorectal liver metastases with CT, MR imaging, FDG PET, and/or FDG PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment.
        Radiology. 2010; 257: 674-684
        • Shinkins B.
        • Nicholson B.D.
        • Primrose J.
        • et al.
        The diagnostic accuracy of a single CEA blood test in detecting colorectal cancer recurrence: results from the FACS trial.
        PLoS One. 2017; 12e0171810
        • Arriola E.
        • Navarro M.
        • Parés D.
        • et al.
        Imaging techniques contribute to increased surgical rescue of relapse in the follow-up of colorectal cancer.
        Dis Colon Rectum. 2006; 49: 478-484
        • Rodríguez-Moranta F.
        • Saló J.
        • Arcusa A.
        • et al.
        Postoperative surveillance in patients with colorectal cancer who have undergone curative resection: a prospective, multicenter, randomized, controlled trial.
        J Clin Oncol. 2006; 24: 386-393
        • Tsikitis V.L.
        • Malireddy K.
        • Green E.A.
        • et al.
        Postoperative surveillance recommendations for early stage colon cancer based on results from the clinical outcomes of surgical therapy trial.
        J Clin Oncol. 2009; 27: 3671-3676
        • Booth C.M.
        • Nanji S.
        • Wei X.
        • Mackillop W.J.
        Management and outcome of colorectal cancer liver metastases in elderly patients: a population-based study.
        JAMA Oncol. 2015; 1: 1111-1119
        • Augestad K.M.
        • Bakaki P.M.
        • Rose J.
        • et al.
        Metastatic spread pattern after curative colorectal cancer surgery. A retrospective, longitudinal analysis.
        Cancer Epidemiol. 2015; 39: 734-744
        • van Gestel Y.R.
        • de Hingh I.H.
        • van Herk-Sukel M.P.
        • et al.
        Patterns of metachronous metastases after curative treatment of colorectal cancer.
        Cancer Epidemiol. 2014; 38: 448-454
        • Sjövall A.
        • Granath F.
        • Cedermark B.
        • Glimelius B.
        • Holm T.
        Loco-regional recurrence from colon cancer: a population-based study.
        Ann Surg Oncol. 2007; 14: 432-440
        • Tepper J.E.
        • O’Connell M.
        • Hollis D.
        • et al.
        Analysis of surgical salvage after failure of primary therapy in rectal cancer: results from Intergroup Study 0114.
        J Clin Oncol. 2003; 21: 3623-3628
        • Landmann R.G.
        • Weiser M.R.
        Surgical management of locally advanced and locally recurrent colon cancer.
        Clin Colon Rectal Surg. 2005; 18: 182-189
        • Tanis P.J.
        • Doeksen A.
        • van Lanschot J.J.
        Intentionally curative treatment of locally recurrent rectal cancer: a systematic review.
        Can J Surg. 2013; 56: 135-144
        • Ayez N.
        • Lalmahomed Z.S.
        • Eggermont A.M.
        • et al.
        Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy.
        Ann Surg Oncol. 2012; 19: 1618-1627
        • Eveno C.
        • Karoui M.
        • Gayat E.
        • et al.
        Liver resection for colorectal liver metastases with peri-operative chemotherapy: oncological results of R1 resections.
        HPB (Oxf). 2013; 15: 359-364
        • Laurent C.
        • Adam J.P.
        • Denost Q.
        • Smith D.
        • Saric J.
        • Chiche L.
        Significance of R1 resection for advanced colorectal liver metastases in the era of modern effective chemotherapy.
        World J Surg. 2016; 40: 1191-1199
        • Lee K.F.
        • Wong J.
        • Cheung Y.S.
        • Ip P.
        • Wong J.
        • Lai P.B.
        Resection margin in laparoscopic hepatectomy: a comparative study between wedge resection and anatomic left lateral sectionectomy.
        HPB (Oxf). 2010; 12: 649-653
        • Leung U.
        • Gönen M.
        • Allen P.J.
        • et al.
        Colorectal cancer liver metastases and concurrent extrahepatic disease treated with resection.
        Ann Surg. 2017; 265: 158-165
        • Tranchart H.
        • Chirica M.
        • Faron M.
        • et al.
        Prognostic impact of positive surgical margins after resection of colorectal cancer liver metastases: reappraisal in the era of modern chemotherapy.
        World J Surg. 2013; 37: 2647-2654
        • Truant S.
        • Séquier C.
        • Leteurtre E.
        • et al.
        Tumour biology of colorectal liver metastasis is a more important factor in survival than surgical margin clearance in the era of modern chemotherapy regimens.
        HPB (Oxf). 2015; 17: 176-184
        • Booth C.M.
        • Nanji S.
        • Wei X.
        • Biagi J.J.
        • Krzyzanowska M.K.
        • Mackillop W.J.
        Surgical resection and peri-operative chemotherapy for colorectal cancer liver metastases: a population-based study.
        Eur J Surg Oncol. 2016; 42: 281-287
        • Booth C.M.
        • Nanji S.
        • Wei X.
        • Mackillop W.J.
        Outcomes of resected colorectal cancer lung metastases in routine clinical practice: a population-based study.
        Ann Surg Oncol. 2016; 23: 1057-1063
        • Giuliante F.
        • Ardito F.
        • Vellone M.
        • et al.
        Role of the surgeon as a variable in long-term survival after liver resection for colorectal metastases.
        J Surg Oncol. 2009; 100: 538-545
        • Hamady Z.Z.
        • Kotru A.
        • Nishio H.
        • Lodge J.P.
        Current techniques and results of liver resection for colorectal liver metastases.
        Br Med Bull. 2004; 70: 87-104
        • Sadot E.
        • Groot Koerkamp B.
        • Leal J.N.
        • et al.
        Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate?.
        Ann Surg. 2015; 262: 476-485
        • Shimizu Y.
        • Yasui K.
        • Sano T.
        • et al.
        Treatment strategy for synchronous metastases of colorectal cancer: is hepatic resection after an observation interval appropriate?.
        Langenbecks Arch Surg. 2007; 392: 535-538
        • Tomlinson J.S.
        • Jarnagin W.R.
        • DeMatteo R.P.
        • et al.
        Actual 10-year survival after resection of colorectal liver metastases defines cure.
        J Clin Oncol. 2007; 25: 4575-4580
        • Abbas S.
        • Lam V.
        • Hollands M.
        Ten-year survival after liver resection for colorectal metastases: systematic review and meta-analysis.
        ISRN Oncol. 2011; 2011763245
        • Pulitanò C.
        • Castillo F.
        • Aldrighetti L.
        • et al.
        What defines ‘cure’ after liver resection for colorectal metastases? Results after 10 years of follow-up.
        HPB (Oxf). 2010; 12: 244-249
        • Simmonds P.C.
        Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group.
        BMJ. 2000; 321: 531-535
        • Cassidy J.
        • Saltz L.
        • Twelves C.
        • et al.
        Efficacy of capecitabine versus 5-fluorouracil in colorectal and gastric cancers: a meta-analysis of individual data from 6171 patients.
        Ann Oncol. 2011; 22: 2604-2609
        • Cassidy J.
        • Clarke S.
        • Díaz-Rubio E.
        • et al.
        XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results.
        Br J Cancer. 2011; 105: 58-64
        • Sanoff H.K.
        • Sargent D.J.
        • Campbell M.E.
        • et al.
        Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741.
        J Clin Oncol. 2008; 26: 5721-5727
        • O’Connell M.J.
        • Campbell M.E.
        • Goldberg R.M.
        • et al.
        Survival following recurrence in stage II and III colon cancer: findings from the ACCENT data set.
        J Clin Oncol. 2008; 26: 2336-2341
      2. United States life tables, 2014. National Center for Health Statistics, Centers for Disease Control and Prevention.
        (Accessed July 15, 2018)
        • Huang L.
        • Cronin K.A.
        • Johnson K.A.
        • Mariotto A.B.
        • Feuer E.J.
        Improved survival time: what can survival cure models tell us about population-based survival improvements in late-stage colorectal, ovarian, and testicular cancer?.
        Cancer. 2008; 112: 2289-2300
        • Klein J.P.
        • Moeschberger M.L.
        Survival Analysis: Techniques for Censored and Truncated Data.
        Springer Science and Business Media, New York, NY2005
        • Meyerhardt J.A.
        • Li L.
        • Sanoff H.K.
        • Carpenter 4th, W.
        • Schrag D.
        Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer.
        J Clin Oncol. 2012; 30: 608-615
        • Scosyrev E.
        • Glimm E.
        Power analysis for multivariable Cox regression models.
        Stat Med. 2019; 38: 88-99
        • O’Hagan A.
        • Stevenson M.
        • Madan J.
        Monte Carlo probabilistic sensitivity analysis for patient level simulation models: efficient estimation of mean and variance using ANOVA.
        Health Econ. 2007; 16: 1009-1023
        • Gonzalez M.
        • Poncet A.
        • Combescure C.
        • Robert J.
        • Ris H.B.
        • Gervaz P.
        Risk factors for survival after lung metastasectomy in colorectal cancer patients: a systematic review and meta-analysis.
        Ann Surg Oncol. 2013; 20: 572-579
        • Harris C.A.
        • Solomon M.J.
        • Heriot A.G.
        • et al.
        The outcomes and patterns of treatment failure after surgery for locally recurrent rectal cancer.
        Ann Surg. 2016; 264: 323-329
        • You Y.N.
        • Skibber J.M.
        • Hu C.Y.
        • et al.
        Impact of multimodal therapy in locally recurrent rectal cancer.
        Br J Surg. 2016; 103: 753-762
        • Ikoma N.
        • You Y.N.
        • Bednarski B.K.
        • et al.
        Impact of recurrence and salvage surgery on survival after multidisciplinary treatment of rectal cancer.
        J Clin Oncol. 2017; 35: 2631-2638
        • Laubert T.
        • Bader F.G.
        • Oevermann E.
        • et al.
        Intensified surveillance after surgery for colorectal cancer significantly improves survival.
        Eur J Med Res. 2010; 15: 25-30
        • Knudsen A.B.
        • Zauber A.G.
        • Rutter C.M.
        • et al.
        Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force.
        JAMA. 2016; 315: 2595-2609
        • Zauber A.G.
        • Lansdorp-Vogelaar I.
        • Knudsen A.B.
        • Wilschut J.
        • van Ballegooijen M.
        • Kuntz K.M.
        Evaluating test strategies for colorectal cancer screening: a decision analysis for the U.S. Preventive Services Task Force.
        Ann Intern Med. 2008; 149: 659-669
        • Lansdorp-Vogelaar I.
        • Knudsen A.B.
        • Brenner H.
        Cost-effectiveness of colorectal cancer screening–an overview.
        Best Pract Res Clin Gastroenterol. 2010; 24: 439-449
        • Wang Y.
        • Li L.
        • Cohen J.D.
        • et al.
        Prognostic potential of circulating tumor DNA measurement in postoperative surveillance of nonmetastatic colorectal cancer.
        JAMA Oncol. 2019; 5: 1118-1123
        • Xie Y.H.
        • Chen Y.X.
        • Fang J.Y.
        Comprehensive review of targeted therapy for colorectal cancer.
        Signal Transduct Target Ther. 2020; 5: 22