■ 664 ■■■■■■■■■■■■■■■■■■■■■■■■■■ Special Topic ■■■■■■■■■■■■■■■■■■■■■■■■■■ ■ 13. Appropriateness of Colonoscopy: Surveillance After Curative Resection of Colorectal Cancer 1 M. Bochud *, B. Burnand *, F. Froehlich **, R. W. Dubois ***, J.-P. Vader *, J.-J. Gonvers ** * Institut Universitaire de Médecine Sociale et Préventive, Lausanne, Switzerland ** Policlinique Médicale Universitaire, Lausanne, Switzerland *** Protocare Sciences, Santa Monica, USA Introduction Almost all cancers of the colon and rectum are carcinomas that develop from the mucosal epithelium. Cancer of the colon and of the rectum are generally considered together under the heading of colorectal cancers. Most of these cancers are adenocarcinomas, and the development of carcinoma from an adenomatous polyp is considered to be the most common developmental feature of colorectal cancer. Patients with previous adenomatous polyps or colorectal cancer have an increased risk of developing a further cancer. In Europe, the annual age-standardized incidence (world population) of colorectal cancer is between 20 and 45 per 100 000 among males and between 15 and 30 per 100 000 among females [1]. Incidence rates increase in a regular fashion with age [1 – 3]. Surveillance monitors people with previously diagnosed colorectal disease: patients who have had polyps (described in a separate article in this issue of the Journal [4]), inflammatory bowel disease (described in a joint article in this issue of the Journal [5]) and colorectal cancer (described in this article) [6]. In November 1998, a multidisciplinary European expert panel convened in Lausanne, Switzerland, to discuss and develop criteria for the appropriate use of gastrointestinal endoscopy, a widely-used procedure, regarded as highly accurate and safe. The RAND appropriateness method was chosen for this purpose, because it allows the development of appropriateness criteria based on published evidence and supplemented by explicit expert opinion. A detailed description of the RAND appropriateness method, including the literature search process [7], and of the whole process, as well as the global results of the panel [8], are published as separate articles in this issue of the Journal. The literature review was based on a systematic search of Medline, Endoscopy 1999; 31 (8): 664 – 672 © Georg Thieme Verlag Stuttgart New York ISSN 0013-726X • Embase and the Cochrane Library conducted up to the end of 1997 and completed with some key articles published in 1998. Updating and revision of the literature review is currently ongoing. This article contains three parts; 1. the review of the literature that was used by the panelists to support their ratings of appropriateness of use of colonoscopic surveillance after curative intent resection of colorectal cancer; 2. an overview of the main panel results; 3. a summary of the published evidence and of the panel based appropriateness criteria. 1. Literature Review Occurrence of Colorectal Cancer Cancer registry-based studies in Finland and Italy have shown an increase in incidence between the 1970s and the 1990s [3, 9]. In the USA, from 1950 to 1984, cancer incidence increased in men and slightly decreased in women, the survival rates increased in both sexes [10]. The US SEER (Surveillance, Epidemiology, and End Results) data for the period 1973 to1992 show a decrease in recent years of the incidence and mortality rates of colorectal cancer [6]. Slight increases in survival have been observed, although these are not always consistent. The cumulative incidence of colorectal cancer in patients with a positive family history (first-degree relative) is higher than for patients with a negative history [11]. The cumulative incidence at age 50 years in patients with a negative history is reached by age 35 – 40 years in those with a positive history [11]. 1 The European Panel on Appropriateness of Gastrointestinal Endoscopy (EPAGE, Lausanne, Switzerland) 13. Appropriateness of Colonoscopy: Surveillance After Curative Resection of Colorectal Cancer Natural History and Symptoms The adenoma-carcinoma sequence has been described in the chapter on polyps [4]. It has been estimated from indirect evidence that it takes an average of 10 years for the transformation of an adenomatous polyp into an invasive cancer [6]. Etiology and Epidemiology The prevalence of adenomas appears to differ by age, gender, race and geographical location, but the relative influence of host versus external factors is not clear. Genetic and environmental factors very probably interact, and their interplay may vary throughout the large intestine [12]. Hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) show an autosomal dominant predisposition, and correspond to 4 – 7 %, and 1 % of all colorectal cancers, respectively [13] while the risk of malignancy is 100 % [14]. The age distribution of colorectal cancer shows a predominance in patients > 50 years with less than 10 % of patients being younger than 50 [15]. A European cancer registry study [16] analyzing 68, 283 colorectal cancer cases found mean ages at diagnosis ranging from 65 to 71.5 years. In a retrospective study [17] of 1,112 patients operated on for colorectal cancer between 1961 and 1980, the authors described a steady increase with secular time in right-sided colonic cancer and a reduction in the overall incidence of rectal and rectosigmoidal carcinoma. This shift in predominance of location to the right colon is confirmed in a population-based cancer register study in the USA [12]. Some authors argue that aging of the population per se may be an important feature in the changing distribution of colorectal cancer [15]. A more frequent incidence of colorectal cancer in the right colon in women and in older patients has been frequently but not always observed [15, 16, 18 – 20]. Endoscopy 1999; 31 665 Inflammatory bowel disease accounts for less than 1 % of all colorectal cancer cases (see corresponding chapter) together with Peutz-Jeghers syndrome and familial juvenile polyposis, in which the colorectal cancer risk is elevated but not to such a great extent as in HNPCC and FAP [6]. Finally, patients with previous adenomatous polyps or colorectal cancer have an increased risk of developing a further cancer. Symptoms Several retrospective studies have examined the proportion of patients with colorectal cancer who had abdominal symptoms and signs prior to diagnosis: general symptoms (general weakness, diarrhea, constipation, weight loss), abdominal pain, change in bowel habits, bleeding, obstruction were commonly, however variously found [22 – 24]. In elderly patients with colorectal cancer, 18 % had abdominal pain, 40 % general symptoms and 38 % blood in the stools. A population-based retrospective study [25] analyzed symptoms at outset and their evolution over time (1940 – 1989): the proportion of symptomatic patients did not significantly differ, but the proportion of patients presenting with an obstruction decreased (from 30 % to 6 %) as well as the proportion of those with a rectal or abdominal mass and abdominal pain. Symptoms of overt bleeding and obstruction are more common with rectosigmoid cancers, weakness and abdominal mass occur more frequently in proximal cancers [6]. However, abdominal pain, constipation, change in stools and diarrhea were not associated with colorectal cancer in a prospective study [26] of 1,223 consecutive colonoscopies. To summarize, symptoms and signs are non-specific indicators of colorectal cancer because they are also frequent in people with other diseases [6]. Risk Factors Histology About 75 % of new cases of colorectal cancer occur in people with no known predisposing factors for the disease, who are considered to be at average risk [6]. The remaining cases occur in patients with a higher-than-average risk. Apart from patients with a genetic predisposition, patients with a family history of colorectal cancer, but without any currently-known genetic susceptibility, account for most of those at high risk (15 – 20 %) [6]. A large American prospective study [11] (combining results from the Nurses Health Study and the Health Professionals Follow-up Study) found an age-adjusted relative risk of colorectal cancer for both sexes of 1.72 (CI95: 1.34 – 2.19) in patients with a positive family history of colorectal cancer (first-degree relatives), with a higher risk among younger people (< 45). Another prospective study [14] and a large casecontrolled study in Utah reported similar results [21]. Young people (< 40) most often present with adenocarcinomas (87 %) mainly of intestinal type and rarely of mucinous (10 %) or other histological types [19]. Mucinous adenocarcinoma are rarer in older patients and occur more frequently in the right colon. Colon-Cancer Survival The Eurocare study [16] carried out a survival analysis on 68 ,283 colon cancer cases diagnosed from 1978 to 1985 in 21 populations in ten European countries. Significant intercountry colon cancer survival differences exist, which cannot be explained either by methodological or by demographic differences. For patients aged 60 to 69 years, the mean European 5-year cumulative relative survival rate was 40 %. However, an improvement in prognosis corresponding to a 4 % reduction in the risk of death per year 666 Endoscopy 1999; 31 M. Bochud et al. was observed in all countries. Age at diagnosis was inversely related to prognosis. A German multicentric observational study [27] in 1,121 patients with invasive rectum cancers found a 5-year survival rate of 55 % for patients without postoperative residual tumours, and 7 % for those with residual tumours. The 5year survival rate for people without distant metastases was 56 % and 8.7 % for those with metastases. Diagnostic Procedures Colonoscopy represents the best diagnostic procedure and has been shown to be superior to rigid sigmoidoscopy plus double contrast barium enema (DCBE) when colonic disease is suspected [28]. Colonoscopy has been shown, in a retrospective study in general clinical practice, to more effectively detect colorectal cancer, especially at an early stage, (sensitivity 97.3 %) than DCBE (sensibility 87 %) [29]. In a large non-randomised controlled trial [30], including 21,000 patients aged 40 years and older, mainly asymptomatic, DCBE missed 25 % of the lesions found at colonoscopy. Therapeutic Endoscopy Early invasive colorectal cancer can be treated locally either by endoscopic or local excision: the reported incidence of lymph node metastases in such cases ranges from 0 to 15.4 %. Kikuchi detected no colorectal cancer-related deaths after a 5-year follow-up [39]. Patients with pedunculated or subpedunculated polyps that can be easily excised by endoscopic polypectomy are at low risk of lymph node metastases. Tumour localisation in the rectum is associated with more lymph node metastases [39]. Patients with submucosal carcinoma invasion should undergo bowel resection [39]. Rationale for Surveillance After Surgical Resection The two main goals of colorectal cancer follow-up are first to detect a recurrence and second to detect new primary cancers, that is metachronous tumours [36, 40]. A prospective study [41] in 321 patients with excision of colonic neoplasms found polyps in 12.5 %, benign strictures in 7.1 %, ulceration in 3.2 % and a carcinoma recurrence in 3.6 % within a period of two years after surgery. Rates of Metachronous Cancers and Cancer Recurrences Several other studies indicated better diagnostic performance by colonoscopy [31, 32]. However, insufficient procedural competence and experience on the part of the endoscopist may decrease test performance [6]. Miss rates are low for adenomas > 1 cm but there are significant miss rates for adenomas < 1 cm [33]. In several retrospective [22, 42] and prospective studies [18, 43, 44], one meta-analysis of follow-up studies of patients operated on curatively [45] and one RCT [37], recurrences occured in approximately one-third of patients (24 – 39 % in follow-up studies) and metachronous cancers were found in 1 – 5 % of patients. Treatment, Surveillance and Prevention Surgery is the primary treatment modality for most colorectal cancers. Special subgroups of patients can benefit from adjuvant chemotherapy or radiotherapy. Nearly twothirds of patients are treated curatively [18, 34], but 26 – 50 % of these will experience a recurrence [35 – 37]. Patients in whom cancer is diagnosed at an early stage have a better survival rate than those with advanced cancers [38] (Table 1). Table 1 Survival rates of patients with colorectal cancer according to Duke’s stage Study Mandel 1993 [39] N Duke's Stage 46 551 5-yr survival (%) A B C D Average 94.3 84.4 56.6 2.4 70.0 Although local recurrences appear to occur frequently, in 47 % of cases, after an average follow-up period of four years [37], intraluminal recurrences are relatively uncommon (6 – 14 %) [43, 46] and metastases are frequent (53 – 54 %) [37, 43]. When Do Recurrences Occur? Most recurrences occur within two years of initial surgery [23, 34, 35, 47, 48]. Few recurrences (1 – 12 %) occur after five years [37, 49, 23, 46]. In a prospective study, the mean time to detection of recurrence ranged from 18 to 27 months [50], from 4 to 156 months in a large but much less recent prospective study [18]. A median time to recurrence of 16.7 months has also been observed [46]. It appears that left-sided primary tumours recur somewhat more often (3 – 9 %) than right sided ones [23, 47, 48, 50], and those more frequently in the rectum [46, 50]. Recurrences According to Primary Tumour Stage A more advanced stage of the primary tumour is associated with a higher recurrence rate [47, 48] (Table 2). Endoscopy 1999; 31 667 13. Appropriateness of Colonoscopy: Surveillance After Curative Resection of Colorectal Cancer Table 2 Recurrences of colorectal cancer according to primary tumour stage Study Pub. date Design N No. (%) of recurrences in Duke’s A No. (%) of No. (%) of No. (%) of No. (%) of Comments recurrences recurrences recurrences recurrences in Duke’s B1 in Duke’s B2 in Duke’s C1 in Duke’s C2 Adloff et al. [48] 1989 cohort 322 (follow-up program) 1/15 (7 %) 5/55 (9 %) 29/146 (20 %) 4/9 (44 %) 53/97 (55 %) Adolff et al. [48] 1989 cohort 587 (no follow-up) 4/66 (6 %) 11/71 (15 %) 98/286 (34 %) 7/15 (47 %) 96/149 (64 %) Mäkelä et al. [55] 1995 RCT 106 10/28 (18 %) 18/48 (37 %) 15/30 (50 %) Kjeldsen et al. [50] Ovaska et al. [36] 1997 RCT 597 (13 %) (20 %) (48 %) 1989 cohort 402 15/1 13 (13 %) 58/212 (27 %) 47/77 (61 %) Symptoms of Recurrent Disease Symptoms of recurrence are abdominal or perineal pain, change in bowel habits, rectal and vaginal bleeding, anorexia and weight loss, cough or bone pain. About one half of recurrent cancers diagnosed are associated with symptoms [18, 23, 51] . Efficacy of Diagnostic Tools to Detect Recurrences Clinical examination has a sensitivity of about 58 – 73 % and a specificity of about 100 % for detection of recurrent cancers [50]. Most blood tests have a low sensitivity and few controlled studies are available to support their use [51]. Increased CEA levels are found in only 25 % of patients with early cancer and in 75 % with advanced cancer. Twenty percent of colorectal cancers do not impact on CEA level. The reported sensitivity of CEA in detecting colorectal cancer recurrence ranges from 58 % to 89 %, and the specificity from 75 % to 98 % [35]. Although numerous studies have examined the possible benefit of CEA in detecting recurrences, no comparative study has demonstrated its usefulness in reducing mortality [35, 51]. Ultrasonography is useful for detecting liver metastases with an estimated sensitivity and specificity of 92 – 94 % and 99 – 100 %, respectively [50]. Thoracic imaging is generally recommended each year for detection of lung metastases [51]. people were included in a regular followup program on a volunteer basis people who refused to have regular follow-up and consulted when symptoms appeared patients of both groups had rather intensive follow-up follow-up 18 – 60 months Double-contrast barium enema is less sensitive for detection of early neoplasia than colonoscopy [32]. The specificity of colonoscopy to detect an intraluminal recurrence is close to 100 % (CI95: 97 – 100) and the sensibility 57 % (CI95: 34 – 78) [50]. However, because most local recurrences are extraluminal, it has been considered that colonoscopy alone is of limited usefulness in the detection of recurrences [43, 51]. Impact of Different Surveillance Programmes on Patient Outcome The rationale for early diagnosis of recurrence is that it could improve the curative resection rate of colorectal cancer [37]. It would thus seem reasonable to think that this could improve the long-term prognosis of patients; however, the evidence currently available in favour of an intensive follow-up programme vs. a less intensive one is weak. A meta-analysis [45] including seven cohort studies (N = 3,283), found no significant difference if all study results were combined. However, a 9 % better 5-year survival rate in patients with intensive follow-up after colorectal cancer surgery was found if only the studies including CEA testing were pooled. In this meta-analysis, the cumulative recurrence rate of patients undergoing intensive follow-up was approximately 16 % at one year, 25 % at two years, 30 % at three years, 34 % at four years and 37 % at five years. These results should be viewed with caution as no randomized controlled trial was available at that time and because the heterogeneity of the follow-up protocols. 668 Endoscopy 1999; 31 Table 3 M. Bochud et al. Randomized controlled trials of various surveillance follow-up programmes after colorectal cancer surgery Study Publication date and place N Sexes (M/F) Age Groups compared Mäkelä 1995 [56] 1995, Finland 106 52/54 63/69 (± 15) conventional intensive vs. intensified follow-up follow-up did not improve 5 year survival of reresectability Ohlsson 1995 [55] 1995, Sweden 107 51/56 65 (40 – 83) intense vs. no follow-up Kjeldsen 1997 [38] 1997, Denmark 597 326/271 <76 intense vs. virtually no follow-up (5, 10 and 15 yr) Northover (unpublisehd) Schoemaker 1998 [57] 1996, UK 1998, Australia 213 207/1 18 69/67 intensive vs. standard follow-up 325 The crucial role of CEA was indeed not supported by many other studies [52, 53]. A recent, thorough and systematic review [35] has identified three published randomized controlled trials [37, 54, 55] and one unpublished study comparing different postoperative surveillance programmes (Table 3). No evidence of an improved survival rate with an intensified follow-up could be demonstrated. Two randomized trials [37, 56] have been published since Richard’s review. In their study, Schoemaker et al. [56] failed to show any benefit from an Main result Definition of intense follow-up history, status, FOBT, blood tests, chest x-ray and CEA every 3 mo for 2 yr and then every 6 mo for 3 yr, liver US every 6 mo, yearly CT history, status, intensive FOBT, blood follow-up tests, chest did not x-ray and CEA improve every 3 mo for survival 2 yr and then every 6 mo for 3 yr, pelvis CT at 3, 6, 12, 18 and 24 mo (those with abdominoperineal resection) no improve- medical history ment in and examinaoverall tion, digital survival or rectal exam, in cancergyn exam, related FOBT, chest, survival x-ray, Hb, ERS, liver enzymes at 6, 12, 18, 24, 30, 48, 60, 120, 150, 180 mo Endoscopic controls in intense follow-up Comment colonoscopy at 3 mo and then yearly the main difference between the 2 groups is liver US and CT rigid sigmoid- lack of oscopy every power to 3 mo for 2 yr detect a difference in and then mortality every 6 mo for 3 yr, colonoscopy at 3, 15, 30 and 60 mo; endoscopic control (colo or sigmo) of the anastomosis at 9, 21 and 42 mo colonoscopy patients in at 6, 12, 18, the intensive 24, 30, 48, follow-up 60, 120, group had 150, 180 mo earlier diagnosis of recurrence and more frequent new surgery with curative intent; no CEA used unpublished study no signifhistory and yearly yearly coloicant differ- clinical exami- colonoscopy noscopy ence in nation, liver CT; failed to desurvival be- colonoscopy, tect any tween the chest x-rays, asymptom2 groups at simple screening atic local 5 years yearly recurrences follow-up intensive follow-up on survival rate and of colonoscopy to detect early recurrences. A Danish study [37] found no improvement of survival rate with intensive follow-up but did, however, report an earlier diagnosis (9 months) and a greater “resectability” of recurrence. Richard et al. [35] further identified five published cohort studies [34, 44, 49, 57, 58] comparing follow-up with no follow-up (four of which were included in Bruinvels metaanalysis). The only study [44] to show a significant reduction in the 5-year mortality rate had significant methodo- 13. Appropriateness of Colonoscopy: Surveillance After Curative Resection of Colorectal Cancer logical weaknesses. In addition, because they were written in foreign languages, Richard et al excluded two cohort studies [48, 59] which indicated favourable results of follow-up compared to no follow-up. One of the cohort studies [44] suggests that highly compliant patients (42 % of patients) have a significantly better survival rate at five years (80 % vs. 59 %, P < 0.002) than non-compliant patients (27 %) and partially compliant patients (32 %). This latter group had the worst outcome, non-compliant patients were older, but the groups compared had similar tumour stages. The specific role of endoscopic surveillance cannot, however, be estimated from these studies, because no study compared groups with and without endoscopy, and the follow-up programmes always included several other tests in addition. From a separate analysis of the characteristics of diagnostic tests in their randomised controlled study [50], Kjeldsen et al. indicated that clinical examination, digital rectal examination, proctoscopy, colonoscopy and chest Xray would be the most useful tests to be included in a follow-up programme. The other diagnostic tests were found to have too low a sensitivity to be useful (blood hemoglobin, FOBT, double-contrast barium enema, liver enzymes). Actually, there are trends moving towards the simplification of surveillance programs. In a clinical update published by the ASGE, Rex emphasised that the primary purpose of surveillance colonoscopy after surgical resection of a colon cancer is to detect metachronous adenomas and not recurrent cancer [60]. If clearing colonoscopy has not been performed preoperatively, it should be done 2 – 3 months postoperatively [60]. Surveillance colonoscopy should then be performed at 3 – 5 year intervals or according to associated polyp findings, similarly to post-polypectomy surveillance: 3 years on average, 5 years after removal of a single tubular adenoma, shorter intervals when numerous adenomas or large sessile adenomas have been removed [60]. Endoscopy 1999; 31 669 Table 4 Definition of terms for screening for colorectal cancer after curative intent resection of a colorectal cancer Adenomas’ features and the associated risk for colorectal cancer. Findings at the previous or index colonoscopy High risk Any of the following: – villous or tubulo-villous histology – size ≥ 1 cm – multiple adenomas – large sessile adenomas – high grade dysplasia Low risk All of the following: – single adenoma – size < 1 cm – tubular histology or non-neoplastic polyp Clinical Variables The clinical variables used for surveillance after curative intent resection of colorectal cancer are shown in Table 5. A series of 3 indications examined the appropriateness of colonoscopy in presence of rising CEA levels in patients with successful colon cancer resection. Table 5 Surveillance following curative intent resection of colorectal cancer (15 items) Variables Number of categories Categories Diagnosis of colonoscopy performed since resection 4 Interval since last colonoscopy 3 Interval since resection 3 2. Panel Results Evaluation done 3 Considering the above review of relevant literature, the panel evaluated 15 specific theoretical patient scenarios related to the use of colonoscopy for surveillance after curative intent resection of colorectal cancer, using an explicit two round modified Delphi panel expert method (RAND appropriateness method) which is described in a joint publication [7]. – no colonoscopy since resection – no polyp or sign of colorectal cancer – low risk polyp – high risk polyp – 1 – < 3 years ago – 3 – < 5 years ago – ≥ 5 years ago – 1 – < 3 years – 3 – < 5 years – ≥ 5 years ago – no abdominal US or CT – abdominal US or CT done, negative – abdominal US or CT done, positive General Panel Results Definition of Terms All terms and definitions were reviewed and approved by the panelists; they are listed in Table 4. Patients with a history of familial adenomatous polyposis (FAP) or a history of non polyposis hereditary colorectal cancer (NPHCC) were excluded. In addition, only patients with a “clean” colon at the index or previous colonoscopy were considered. Surveillance following curative intent resection of colorectal cancer was assessed in 15 clinical scenarios. Four scenarios were rated as inappropriate, 1 as uncertain and 10 as appropriate. Agreement between panelists was obtained in 10/15 scenarios. 670 Endoscopy 1999; 31 Specific Clinical Panel Results The main results are worded as an overall statement representing several clinical scenarios in Table 6. In some cases, the same scenario may apply to more than one statement. Detailed appropriateness and necessity criteria are available in a computerized form accessible via Internet (http:// www.epage.ch). Table 6 Description of appropriateness of indications for colonoscopy for surveillance after curative intent resection of colorectal cancer Clinical situation In individuals who received no colonoscopy since curative intent resection of colorectal cancer, indication for colonoscopy is appropriate after 5 years of follow-up (possibly appropriate after 1 year of follow-up) In individuals who received at least one colonoscopy since curative intent resection of colorectal cancer, indication for colonoscopy is appropriate – after 1 year of follow-up if last surveillance colonoscopy showed high risk adenomas – after 3 years of follow-up if last surveillance colonoscopy showed low risk adenomas – after 5 years of follow-up if last surveillance colonoscopy showed no adenomas and no cancer inappropriate – before 3 years of follow-up if last surveillance colonoscopy showed no or low risk adenomas and no cancer In individuals with rising CEA levels, indication for colonoscopy is appropriate in presence of a negative abdominal imaging (US*, CT1) * US: ultrasonography, 1 CT: computed tomography Description of Necessity Three out of the fifteen scenarios were judged necessary (20 %). Essentially, if no colonoscopy has been performed since curative intent resection of a colorectal cancer, it has been considered necessary to perform a colonoscopy after 5 years of follow-up. If a follow-up colonoscopy has already been performed, a subsequent colonoscopy is necessary after 3 years if high risk adenomas were found at the surveillance colonoscopy. In presence of rising CEA levels, in no situation was colonoscopy considered necessary. 3. Conclusions Although colonoscopy has been considered to be an essential diagnostic tool in a surveillance programme after curative intent resection of a colorectal cancer [48], the available evidence from RCTs and systematic reviews does not indicate a major improvement of survival rate with an intensive follow-up including colonoscopy. A small improvement in survival (20 % or less) cannot be definitely excluded. Colonoscopy has been considered as possibly useful to detect metachronous cancers, and it has been suggested M. Bochud et al. that a schedule similar to post-polypectomy surveillance should be used [6, 60]. Despite this relatively poor scientific evidence, surveillance colonoscopy was often considered appropriate by the multidisciplinary panel at some point after curative intent resection of a colorectal cancer. Subsequent follow-up colonoscopies were essentially considered appropriate, and sometimes also necessary, according to the level of risk of developing a new cancer (e.g. sooner in presence of high risk adenomas). Acknowledgement The authors gratefully acknowledge the selfless commitment and invaluable contribution of the expert panel members, who made this project possible: Marcello Anti (IT), Peter Bytzer (DK), Mark Cottrill (UK), Michael Fried (CH), Roar Johnsen (NO), Gerd Kanzler (DE), François Lacaine (FR), Cornelis Lamers (NL), Roger J. Leicester (UK), Mattijs E. Numans (NL), Javier P. Piqueras (ES), Jean-François Rey (FR), Giacomo Sturniolo (IT), Robert P. Walt (UK). 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