Postoperative surveillance in nonmetastatic colorectal cancer patients: yes, but…

Abstract

Colorectal cancer (CRC) is a major health problem. In Western countries, it represents the most prevalent neoplasm and the second leading cause of cancer-related death [1.Ferlay J. Shin H.R. Bray F. et al.Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.Int J Cancer. 2010; 127: 2893-2917Crossref PubMed Scopus (13637) Google Scholar]. Prognosis of these patients mainly depends on the tumor stage at diagnosis. In fact, although more than two thirds of patients undergo curative-intent surgery, up to 30% of those with stage II–III tumors will develop tumor relapse as locoregional recurrence, distant metastasis or metachronous colorectal neoplasms during follow-up [2.Safi F. Beyer H.G. The value of follow-up after curative surgery of colorectal carcinoma.Cancer Detect Prev. 1993; 17: 417-424PubMed Google Scholar,3.Rodriguez-Moranta F. Salo 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: 386-393Crossref PubMed Scopus (235) Google Scholar]. This high risk of disease recurrence makes postoperative surveillance advisable, given that early treatment of tumor relapse seems to be critical to improve patients' prognosis [4.Winawer S. Fletcher R. Rex D. et al.Colorectal cancer screening and surveillance: clinical guidelines and rationale—update based on new evidence.Gastroenterology. 2003; 124: 544-560Abstract Full Text PDF PubMed Scopus (1983) Google Scholar, 5.Benotti P. Steele Jr, G. Patterns of recurrent colorectal cancer and recovery surgery.Cancer. 1992; 70: 1409-1413Crossref PubMed Scopus (29) Google Scholar, 6.Turk P.S. Wanebo H.J. Results of surgical treatment of non-hepatic recurrence of colorectal carcinoma.Cancer. 1993; 71: 4267-4277Crossref PubMed Scopus (112) Google Scholar]. Indeed, guidelines from most expert groups, including the European Society for Medical Oncology [7.Labianca R. Nordlinger B. Beretta G.D. et al.Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi64-vi72Abstract Full Text Full Text PDF PubMed Scopus (658) Google Scholar,8.Glimelius B. Tiret E. Cervantes A. Arnold D. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi81-vi88Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar], the American Society of Clinical Oncology [9.Desch C.E. Benson III, A.B. Somerfield M.R. et al.Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline.J Clin Oncol. 2005; 23: 8512-8519Crossref PubMed Scopus (471) Google Scholar], the American Society of Gastrointestinal Endoscopy [10.Davila R.E. Rajan E. Baron T.H. et al.ASGE guideline: colorectal cancer screening and surveillance.Gastrointest Endosc. 2006; 63: 546-557Abstract Full Text Full Text PDF PubMed Scopus (288) Google Scholar], and the National Comprehensive Cancer Network [11.National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology. Colon cancer. 2011; (v3)Google Scholar], recommend intensive postoperative surveillance for patients with resected stage II and III CRC who would be considered candidates for aggressive treatment (i.e. surgery). Although the above-mentioned agreement on the usefulness of postoperative surveillance, no consensus has been reached so far regarding the most effective and efficient strategy. Indeed, follow-up schedules are highly heterogeneous with respect to both procedures, which include periodic history and physical examination, carcinoembryonic antigen (CEA) monitoring, imaging techniques (i.e. computed tomography scanning) and colonoscopy, and the frequency they should be carried out [7.Labianca R. Nordlinger B. Beretta G.D. et al.Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi64-vi72Abstract Full Text Full Text PDF PubMed Scopus (658) Google Scholar, 8.Glimelius B. Tiret E. Cervantes A. Arnold D. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi81-vi88Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar, 9.Desch C.E. Benson III, A.B. Somerfield M.R. et al.Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline.J Clin Oncol. 2005; 23: 8512-8519Crossref PubMed Scopus (471) Google Scholar, 10.Davila R.E. Rajan E. Baron T.H. et al.ASGE guideline: colorectal cancer screening and surveillance.Gastrointest Endosc. 2006; 63: 546-557Abstract Full Text Full Text PDF PubMed Scopus (288) Google Scholar, 11.National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology. Colon cancer. 2011; (v3)Google Scholar]. It is important to point out that this heterogeneity occurs albeit 11 randomized, controlled trials and 6 meta-analyses [12.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: 26Crossref PubMed Scopus (310) Google Scholar, 13.Jeffery G.M. Hickey B.E. Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer.Cochrane Database Syst Rev. 2002; : CD002200PubMed Google Scholar, 14.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: 813-816Crossref PubMed Google Scholar, 15.Renehan A.G. Egger M. Saunders M.P. O'Dwyer S.T. Mechanisms of improved survival from intensive follow-up in colorectal cancer: a hypothesis.Br J Cancer. 2005; 92: 430-433Crossref PubMed Scopus (42) Google Scholar, 16.Tjandra J.J. Chan M.K. Follow-up after curative resection of colorectal cancer: a meta-analysis.Dis Colon Rectum. 2007; 50: 1783-1799Crossref PubMed Scopus (276) Google Scholar, 17.Jeffery M. Hickey B.E. Hider P.N. Follow-up strategies for patients treated for non-metastatic colorectal cancer.Cochrane Database Syst Rev. 2007; : CD002200PubMed Google Scholar] have addressed such a goal, thus emphasizing the intrinsic difficulty of this topic. In thisAnnals of Oncology issue, Pita-Fernández et al. report a meticulous, well-performed and updated systematic review and meta-analysis to provide further evidence of different follow-up strategies in patients with non-metastatic CRC after curative surgery [18.Pita-Fernandez S. Alhayek-Ai M. Gonzalez-Martin C. et al.Intensive follow-up strategies improve outcomes in non-metastatic colorectal cancer patients after curative surgery. A systematic review and meta-analysis.Ann Oncol. 2015; 26: 644-656Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar]. These authors compiled 11 randomized, controlled trials, totaling 4055 patients (2330 men and 1725 women) with stage I–III colon or rectal cancer operated on for cure, in which patients were allocated to either intensive, less intensive or no follow-up. In this meta-analysis, a more intensive surveillance strategy was associated with a significant improvement of overall survival [hazard rate (HR), 0.75; 95% confidence interval (95% CI) 0.66–0.86]. Similarly, intensive follow-up was also associated with a higher probability of detecting asymptomatic disease recurrence [relative risk (RR), 2.59; 95% CI 1.66–4.06], of curative-intent surgery at recurrence (RR, 1.98; 95% CI 1.51–2.60), and of survival after tumor relapse (RR, 2.13; 95% CI 1.24–3.69), as well as a shorter time in detecting recurrences (mean difference, -5.23 months; 95% CI -0.88 to -9.58 months). Interestingly, however, no significant difference was observed with respect to CRC-related survival (RR, 0.91; 95% CI 0.74–1.10) [18.Pita-Fernandez S. Alhayek-Ai M. Gonzalez-Martin C. et al.Intensive follow-up strategies improve outcomes in non-metastatic colorectal cancer patients after curative surgery. A systematic review and meta-analysis.Ann Oncol. 2015; 26: 644-656Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar]. Strengths of this study are the number of patients included, thus representing the largest meta-analysis carried out to date, the use of an accurate methodology that allowed to calculate the HR when evaluating overall survival and, finally, the comprehensive nature of outcomes evaluated including, for the first time, patients' survival once recurrences were detected [18.Pita-Fernandez S. Alhayek-Ai M. Gonzalez-Martin C. et al.Intensive follow-up strategies improve outcomes in non-metastatic colorectal cancer patients after curative surgery. A systematic review and meta-analysis.Ann Oncol. 2015; 26: 644-656Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar]. As previous meta-analyses [12.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: 26Crossref PubMed Scopus (310) Google Scholar, 13.Jeffery G.M. Hickey B.E. Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer.Cochrane Database Syst Rev. 2002; : CD002200PubMed Google Scholar, 14.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: 813-816Crossref PubMed Google Scholar, 15.Renehan A.G. Egger M. Saunders M.P. O'Dwyer S.T. Mechanisms of improved survival from intensive follow-up in colorectal cancer: a hypothesis.Br J Cancer. 2005; 92: 430-433Crossref PubMed Scopus (42) Google Scholar, 16.Tjandra J.J. Chan M.K. Follow-up after curative resection of colorectal cancer: a meta-analysis.Dis Colon Rectum. 2007; 50: 1783-1799Crossref PubMed Scopus (276) Google Scholar, 17.Jeffery M. Hickey B.E. Hider P.N. Follow-up strategies for patients treated for non-metastatic colorectal cancer.Cochrane Database Syst Rev. 2007; : CD002200PubMed Google Scholar], this study has some limitations. First, the evaluated randomized, controlled studies were tremendously heterogeneous with respect to the assessed strategies, including type of procedures and periodicity in both the intervention and the control arms, length of follow-up, and setting in which surveillance was carried out. This circumstance precludes delineating the optimal follow-up strategy. Second, epidemiological, clinical and tumor characteristics associated with different likelihoods of tumor recurrence (i.e. tumor location and stage) [3.Rodriguez-Moranta F. Salo 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: 386-393Crossref PubMed Scopus (235) Google Scholar] or colorectal metachronous neoplasms (i.e. age, gender, family history, and presence of synchronous colorectal lesions) [19.Castells A. Castellvi-Bel S. Balaguer F. Concepts in familial colorectal cancer: where do we stand and what is the future?.Gastroenterology. 2009; 137: 404-409Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 20.Moreira L. Balaguer F. Lindor N. et al.Identification of Lynch syndrome among patients with colorectal cancer.JAMA. 2012; 308: 1555-1565Crossref PubMed Scopus (372) Google Scholar, 21.Balleste B. Bessa X. Pinol V. et al.Detection of metachronous neoplasms in colorectal cancer patients: identification of risk factors.Dis Colon Rectum. 2007; 50: 971-980Crossref PubMed Scopus (56) Google Scholar] could not be taken into account, thus prompting the identification of a unique surveillance strategy under the common assumption that ‘one size fits all’. Finally, no distinction was made with respect to the type of tumor relapse, although the pathogenic mechanisms underlying locoregional proliferation, metastatic spread and metachronicity are very different [22.Lacy A.M. Garcia-Valdecasas J.C. Delgado S. et al.Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial.Lancet. 2002; 359: 2224-2229Abstract Full Text Full Text PDF PubMed Scopus (2086) Google Scholar,23.Gonzalo V. Lozano J.J. Alonso-Espinaco V. et al.Multiple sporadic colorectal cancers display a unique methylation phenotype.PLoS One. 2014; 9: e91033Crossref PubMed Scopus (7) Google Scholar]. One of the most intriguing aspects of this meta-analysis [18.Pita-Fernandez S. Alhayek-Ai M. Gonzalez-Martin C. et al.Intensive follow-up strategies improve outcomes in non-metastatic colorectal cancer patients after curative surgery. A systematic review and meta-analysis.Ann Oncol. 2015; 26: 644-656Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar], as well as of the previous ones [12.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: 26Crossref PubMed Scopus (310) Google Scholar, 13.Jeffery G.M. Hickey B.E. Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer.Cochrane Database Syst Rev. 2002; : CD002200PubMed Google Scholar, 14.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: 813-816Crossref PubMed Google Scholar, 15.Renehan A.G. Egger M. Saunders M.P. O'Dwyer S.T. Mechanisms of improved survival from intensive follow-up in colorectal cancer: a hypothesis.Br J Cancer. 2005; 92: 430-433Crossref PubMed Scopus (42) Google Scholar, 16.Tjandra J.J. Chan M.K. Follow-up after curative resection of colorectal cancer: a meta-analysis.Dis Colon Rectum. 2007; 50: 1783-1799Crossref PubMed Scopus (276) Google Scholar, 17.Jeffery M. Hickey B.E. Hider P.N. Follow-up strategies for patients treated for non-metastatic colorectal cancer.Cochrane Database Syst Rev. 2007; : CD002200PubMed Google Scholar], is the discrepancy between overall and disease-specific survival. Indeed, whereas intensive surveillance was associated with a 25% improvement of overall survival, no effect was observed on CRC-related mortality. Although a type II error due to an insufficient sample size may explain the lack of difference on the latter result, this explanation is quite unlikely since the study was powered to demonstrate differences in other secondary outcomes (i.e. detection of asymptomatic recurrences, probability of curative-intent surgery, survival after tumor relapse, and time to detect tumor relapse). Therefore, a potential selection bias favoring the intervention group on terms of overall survival cannot be definitively ruled out. Assuming that early diagnosis of asymptomatic recurrence increases the likelihood of a complete surgical resection, and that a modest, but significant, survival benefit is achieved using an intensive follow-up strategy, then the one-million question is which surveillance tests should be used. Unfortunately, results from Fernández-Pita et al. meta-analysis [18.Pita-Fernandez S. Alhayek-Ai M. Gonzalez-Martin C. et al.Intensive follow-up strategies improve outcomes in non-metastatic colorectal cancer patients after curative surgery. A systematic review and meta-analysis.Ann Oncol. 2015; 26: 644-656Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar] do not provide any additional information with respect to the individual value of clinical, serological, endoscopic and imaging exams, since most of them were carried out simultaneously. In spite of this fact, most published guidelines [7.Labianca R. Nordlinger B. Beretta G.D. et al.Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi64-vi72Abstract Full Text Full Text PDF PubMed Scopus (658) Google Scholar, 8.Glimelius B. Tiret E. Cervantes A. Arnold D. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi81-vi88Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar, 9.Desch C.E. Benson III, A.B. Somerfield M.R. et al.Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline.J Clin Oncol. 2005; 23: 8512-8519Crossref PubMed Scopus (471) Google Scholar, 10.Davila R.E. Rajan E. Baron T.H. et al.ASGE guideline: colorectal cancer screening and surveillance.Gastrointest Endosc. 2006; 63: 546-557Abstract Full Text Full Text PDF PubMed Scopus (288) Google Scholar, 11.National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology. Colon cancer. 2011; (v3)Google Scholar] suggest that there is enough evidence to recommend a clinical encounter every 3–6 months for the first 2 years, and every 6 months during years 3–5, as well as serum CEA testing at each follow-up visit. Moreover, it is highly recommended that all CRC patients undergo a complete colonoscopy either before surgery or within a few months after resection to exclude synchronous neoplasms, and to repeat it 1 year after surgical resection to rule out metachronous lesions; intervals between subsequent examinations will be established depending on the results of the previous colonoscopy. On the other hand, although there is less evidence, most expert panels also recommend to perform abdomen and chest computed tomography scanning every 6–12 months for the first 3 years. Finally, other exams, such as fecal occult blood testing, liver function tests, complete blood count, chest X-ray, and PET scanning, should not be included in routine surveillance [7.Labianca R. Nordlinger B. Beretta G.D. et al.Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi64-vi72Abstract Full Text Full Text PDF PubMed Scopus (658) Google Scholar, 8.Glimelius B. Tiret E. Cervantes A. Arnold D. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2013; 24: vi81-vi88Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar, 9.Desch C.E. Benson III, A.B. Somerfield M.R. et al.Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline.J Clin Oncol. 2005; 23: 8512-8519Crossref PubMed Scopus (471) Google Scholar, 10.Davila R.E. Rajan E. Baron T.H. et al.ASGE guideline: colorectal cancer screening and surveillance.Gastrointest Endosc. 2006; 63: 546-557Abstract Full Text Full Text PDF PubMed Scopus (288) Google Scholar, 11.National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology. Colon cancer. 2011; (v3)Google Scholar]. In summary, besides increasing our efforts to decrease CRC incidence by means of full-extended, nation-wide screening programs [24.Quintero E. Castells A. Bujanda L. et al.Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening.N Engl J Med. 2012; 366: 697-706Crossref PubMed Scopus (664) Google Scholar], postoperative surveillance seem to be a rational approach to reduce mortality in those patients who eventually develop such a disease.