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Background: Adjuvant chemotherapy after curative resection for rectal cancer is the standard of care in several American and European guidelines., Objective: The aim of this study was to examine the differences in health-related quality of life over time between patients with rectal cancer who were treated with adjuvant chemotherapy or observation., Design: This is a randomized controlled phase III trial., Settings: Health-related quality-of-life assessments were conducted in Dutch patients from 43 institutes., Patients: Patients with stage II or III rectal cancer who underwent preoperative (chemo)radiotherapy followed by curative surgery (the SCRIPT trial) were included., Interventions: Patients were randomly assigned to adjuvant capecitabine monotherapy for 8 cycles or observation. Health-related quality of life was assessed using the European Organization for Research and Treatment of Cancer C30 and CR38 questionnaires at 1 month after surgery (before the start of chemotherapy), and 3, 6, and 12 months after surgery., Main Outcome Measures: The primary outcome measure was the difference in quality of life at 6 months after surgery, just after completion of adjuvant chemotherapy for patients in the treatment group. Second, the difference in health-related quality of life at 12 months after surgery was examined. A statistically significant difference of 5 points was considered clinically relevant., Results: Health-related quality-of-life results of 226 of 233 patients were available. At T3, overall quality of life (C30 summary score) was worse for patients treated with chemotherapy compared with observation (mean 82.3 versus 86.9, p = 0.006), but the difference was not clinically relevant. Patients treated with adjuvant chemotherapy reported clinically relevant worse physical functioning (mean 78.3 versus 87.0, p < 0.001) and more reports of fatigue and dyspnea (35.7 versus 21.0 and 17.1 versus 6.7, p < 0.001). All differences were resolved at 12 months postsurgery., Limitations: A selection of relatively fit patients willing to be randomly assigned may limit the generalizability of the results., Conclusions: Although inferior health-related quality of life was reported just after completion of adjuvant chemotherapy, no persistent deterioration in quality of life was detected. See Video Abstract at http://links.lww.com/DCR/A907.

Background: For patients with asymptomatic, incurable, metastatic colorectal cancer, palliative, systemic treatment can be started immediately, or can be delayed until disease-related symptoms occur. How the potential survival benefit of starting palliative, systemic treatment immediately after diagnosis weighs up against the potential side effects is currently under debate, and was investigated in this review., Objectives: To assess the effects of immediate versus delayed chemotherapy, with or without targeted therapy, on overall survival, toxicity, quality of life, progression-free survival, and compliance with chemotherapy for individuals with asymptomatic, metastatic, incurable colorectal cancer., Search Methods: We searched CENTRAL; 2018, Issue 8, MEDLINE Ovid, Embase Ovid, PsycINFO, the World Health Organization International Clinical Trials Registry Platform, and Clinicaltrials.gov, from inception to 23 August 2018. We did not apply limitations based on language or date of publication. We searched the reference lists of all included studies to identify trials that may not have been identified from the electronic searches., Selection Criteria: Randomised controlled trials evaluating immediate versus delayed chemotherapy in persons with asymptomatic, metastatic, incurable colorectal cancer., Data Collection and Analysis: We applied standard methodological procedures, according to the recommendations of Cochrane and Cochrane Colorectal Cancer. Two review authors independently reviewed the studies identified by literature searches, selected relevant trials, extracted data, and assessed risk of bias of the included studies. We used the Cochrane tool to assess risk of bias, Review Manager 5 software for meta-analysis, GRADE methods to evaluate the quality of the evidence, and GRADEpro GDT software to develop a 'Summary of findings' table., Main Results: We included three randomised controlled trials (351 participants) investigating immediate versus delayed chemotherapy in people diagnosed with asymptomatic, metastatic, incurable colorectal cancer. Giving immediate versus delayed chemotherapy may make little or no difference to overall survival (hazard ratio (HR) 1.17, 95% confidence interval (CI) 0.93 to 1.46; 3 studies, 351 persons; low-quality evidence). For toxicity, giving immediate versus delayed chemotherapy may make little or no difference to the risk of grade 3 or 4 nausea and vomiting (risk ratio (RR) 0.84, 95% CI 0.31 to 2.25; 2 studies, 140 persons; very low-quality evidence), stomatitis (RR 1.10, 95% CI 0.47 to 2.55; 2 studies, 140 persons; very low-quality evidence), or diarrhoea (RR 0.69, 95% CI 0.34 to 1.40; 2 studies, 140 persons, very low-quality evidence). We are uncertain whether delayed chemotherapy made a difference to quality of life (very low-quality evidence), progression-free survival (low-quality evidence), or compliance with chemotherapy (low-quality evidence), as we had insufficient data to pool for these outcomes., Authors' Conclusions: Based on a limited number of trials, very sparse data, and uncertainty of the evidence, this review was unable to establish whether there was a difference in overall survival or other clinically relevant outcomes, between immediate or delayed chemotherapy in persons with metastatic, incurable, colorectal cancer. The results should be interpreted with caution.

Background: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME)., Patients and Methods: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival., Results: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39)., Conclusion: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual., Registration Number: Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer., Methods and Design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life., Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer., Trial Registration: ClinicalTrials.gov NCT01558921.

Purpose: Radiotherapy is a very effective adjuvant treatment for rectal cancer with little side effects. Its killing effect on tumor cells seems to be more profound than the effect on normal tissue. The molecular events caused by irradiation are mainly analyzed in in vitro and animal models; investigations on human material are rare. In the current study, we analyzed the effects of irradiation on gene expression in normal and tumor tissue of rectal cancer patients., Methods and Materials: Normal and carcinoma tissue of patients from a randomized clinical trial of the benefits of preoperative radiotherapy were analyzed using the Affymetrix Human Cancer Gene Chip. Preoperative radiotherapy was given within 5 days prior to surgery. Results for normal tissue and tumor were compared to investigate the radiation-related differences between normal and tumor cells. We clustered the differentially expressed genes based on their functional annotation. Results were compared with immunohistochemical and literature data., Results: The majority of the investigated cancer-related genes remained unchanged by irradiation (92% in tumor tissue and 93% in normal tissue). The differentially expressed genes varied between tumor and normal tissue except for maspin and IL-8. Both in tumor and normal tissue, differentially expressed genes were present related to cell signaling and cycle control, apoptosis and cell survival and tissue response and repair. However, the spectrum of affected genes was totally different., Conclusion: Pre-existing differences in gene expression between normal tissue and tumor tissue might explain the differences in their responses to radiation. This change in response may explain the clinical beneficial effect of radiotherapy on tumor cells (low local recurrence rate) and the less severe effects on normal tissue (minor side effects).

One of the major problems in the treatment of rectal cancer has been the inability to achieve local control. Traditional surgery, now outmoded, involves blunt digital dissection and was associated with a high incidence of local recurrence. In an attempt to improve local control and survival, many adjuvant treatment modalities have been investigated. In the context of conventional nonstandardized surgical procedures, pre-operative radiotherapy has been shown to improve local control and overall survival. In recent years treatment outcome has been extensively improved by the introduction of the TME technique first described by Heald. This has resulted in such low recurrence rates and improved survival that the question had to be answered whether pre-operative short-term radiotherapy is still beneficial in TME treated patients. The question was answered in the TME trial set up by the Dutch ColoRectal Cancer Group that randomised between standardized and quality-controlled TME surgery alone and TME surgery preceded by short-term pre-operative radiotherapy. This paper reviews the developments in the treatment of resectable rectal cancer, highlights the results from the Dutch TME trial, and considers future directions in improving outcome.

Purpose: Circumferential resection margin (CRM) involvement is a prognostic factor for local recurrence in rectal cancer. In a randomized trial comparing preoperative radiotherapy (5 x 5 Gy), followed by total mesorectal excision (TME) with TME alone, we demonstrated the beneficial effect of short-term preoperative radiotherapy on local recurrences. Here we evaluate the effect of radiotherapy on local recurrence rates in patients with different CRM involvements., Methods and Materials: Circumferential margins were defined as positive (< or =1 mm), narrow (1.1-2 mm), or wide (>2 mm). Postoperative radiotherapy was mandatory for surgery-only patients with a positive CRM, but was not always administered and enabled us to compare local recurrence rates for patients with or without postoperative radiotherapy. Furthermore, the effect of preoperative radiotherapy was assessed in the different margin groups., Results: Of 120 patients in the surgery-only group with a positive CRM, 47% received postoperative radiotherapy. There was no difference in the local recurrence rate between the irradiated and nonirradiated patients (17.3% vs. 15.7%, p = 0.98). Preoperative radiotherapy was effective in patients with a narrow CRM (0% vs. 14.9%, p = 0.02) or wide CRM (0.9 vs. 5.8%, p < 0.0001), but not in patients with positive margins (9.3% vs. 16.4%, p = 0.08)., Conclusion: Preoperative hypofractionated radiotherapy has a beneficial effect in patients with wide or narrow resection margins, but cannot compensate for microscopically irradical resections resulting in positive margins.

Background: Local control and survival following surgical treatment of rectal cancer have been improved by the introduction of total mesorectal excision (TME). The aim of this study was to determine the nationwide impact of the introduction and training of TME on recurrence and survival in rectal cancer., Methods: Short- and long-term outcomes of a recently published trial of rectal cancer surgery (TME trial) were compared with results from an older trial (cancer recurrence and blood transfusion (CRAB) trial), in which conventional surgery was performed without quality control. Only patients who were operated on with curative intent and who did not receive neoadjuvant radiotherapy were studied. Differences in clinicopathological characteristics were corrected for by multivariate analysis. To ensure valid comparisons, only events that occurred within 2 years of operation were analysed with regard to long-term outcome., Results: In the univariate analysis, a higher clinical anastomotic leak rate was found in patients following low anterior resection in the TME trial (P = 0.046), but this association was not significant in the multivariate analysis. The local recurrence rate decreased from 16 per cent in the CRAB trial to 9 per cent in the TME trial, and type of operation (conventional (CRAB trial) versus TME (TME trial)) was an independent predictor of local recurrence (P = 0.002). Type of operation was also an independent predictor of overall survival (P = 0.019); there was a higher survival rate in the TME trial., Conclusion: The introduction and training of TME has led to improved long-term outcome of patients with rectal cancer in the Netherlands.

One of the main problems in the treatment of rectal cancer is the development of local recurrences. In the last decades, major improvements have been realized in the surgical treatment of rectal cancer. The introduction of TME-surgery has led to a large reduction in local recurrence rates and improved survival. TME-based operations are now established as the standard of care for rectal cancer, and should form the basis for trials concerning the role of (neo)adjuvant therapy. However, training and quality control are prerequisites to obtain good results in all surgeons' hands. Furthermore, standardization in the description of operations and reporting of pathology specimens should be implemented as important features of quality control. In general, it is thought that high volume and specialist care produces superior results to low volume and non-specialist care, especially for those less frequent forms of cancer and in technically difficult operations, like those for rectal cancer. However, limiting the performance of rectal cancer surgery to highly specialized surgeons or to only those general surgeons who perform more than a certain volume is impractical in view of the prevalence of rectal cancer. This article reviews developments in the treatment of especially mobile rectal cancer and pays attention to variability in outcomes and quality assurance of surgery.

Purpose: Quality assessment and assurance are important issues in modern health care. For the evaluation of surgical procedures, there are indirect parameters such as complication, recurrence, and survival rates. These parameters are of limited value for the individual surgeon, and there is an obvious need for direct parameters. We have evaluated criteria by which pathologists can judge the quality or completeness of the resection specimen in a randomized trial for rectal cancer., Patients and Methods: The pathology reports of all patients entered onto a Dutch multicenter randomized trial were reviewed. All participating pathologists had been instructed by workshops and videos in order to obtain standardized pathology work-up. A three-tiered classification was applied to assess completeness of the total mesorectal excision (TME). Prognostic value of this classification was tested using log-rank analysis of Kaplan-Meier survival curves using the data of all patients who did not receive any adjuvant treatment., Results: Included were 180 patients. In 24% (n = 43), the mesorectum was incomplete. Patients in this group had an increased risk for local and distant recurrence, 36.1% v. 20.3% recurrence in the group with a complete mesorectum (P =.02). Follow-up is too short to observe an effect on survival rates., Conclusion: A patient's prognosis is predicted by applying a classification of macroscopic completeness on a rectal resection specimen. We conclude that pathologists are able to judge the quality of TME for rectal cancer. With this direct interdisciplinary assessment instrument, we establish a new role of the pathologist in quality control.

Purpose: In vitro, ionizing radiation of epithelial cells leads to upregulation of wild-type p53 and subsequent induction of p21(waf1). The effect of radiotherapy (RT) on the expression of these proteins in patients is unknown. We assessed the influence of RT on the expression of p53 and p21(waf1) in normal mucosa and rectal carcinomas in vivo., Methods: Tumor and normal tissue samples were derived from rectal cancer patients randomized in a clinical trial in which the value of preoperative RT was evaluated. p53 and p21(waf1) expression was determined in 51 irradiated and 52 nonirradiated patients using immunohistochemistry., Results: In normal mucosa, both p53 and p21(waf1) were strongly upregulated after RT compared with the expression in unirradiated normal tissue (p <0.001). In tumor cells, no significant difference in the expression of p53 or p21(waf1) was found in the irradiated vs. nonirradiated group. In the few rectal tumors with wild-type p53, induction of p53 after RT did not necessarily lead to upregulation of p21(waf1)., Conclusion: These findings demonstrate that in normal mucosa, a functional p53-p21(waf1) pathway is present, whereas in tumor cells it is defective in almost all cases because of either p53 mutation or down- or upstream disruption in tumors with wild-type p53. Therefore, we believe that the role of p53 expression as a single prognostic marker in rectal cancer needs reconsideration.

Purpose: Total mesorectal excision (TME) surgery in the treatment of rectal cancer has been shown to result in a reduction in the number of local recurrences in retrospective studies. Reports on improved local control after preoperative, hypofractionated radiotherapy (RT) have led to the introduction of a prospective randomized multicenter trial, in which the effect of TME surgery with or without preoperative RT were evaluated. Any benefit in regard to a reduced local recurrence rate and possible improved survival must be weighed against potential adverse effects in both the short-term and the long-term. The present study was undertaken to assess the acute side effects of short-term, preoperative RT in rectal cancer patients and to study the influence of five doses of 5 Gy on surgical parameters, postoperative morbidity and mortality in patients randomized in the Dutch TME trial., Patients and Methods: We analyzed 1,530 Dutch patients entered onto a prospective randomized trial, comparing preoperative RT with five doses of 5 Gy followed by TME surgery with TME surgery alone, of which 1,414 patients were assessable. Toxicity from RT, surgery characteristics, and postoperative complications and mortality were compared., Results: Toxicity during RT hardly occurred. Irradiated patients had 100 mL more blood loss during the operation (P <.001) and showed more perineal complications (P =.008) in cases of abdominoperineal resection. The total number of complications was slightly increased in the irradiated group (P =.008). No difference was observed in postoperative mortality (4.0% v 3.3%) or in the number of reinterventions., Conclusion: Preoperative hypofractionated RT is a safe procedure in patients treated with TME surgery, despite a slight increase in complications when compared with TME surgery only.

Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42 rectal cancers. Rectal cancer patients had been treated with standardized surgery performed by an experienced rectal cancer surgeon. Mutation analysis was performed for p53 in eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl-2, p53, E-cadherin and beta-catenin were investigated by immunohistochemistry in all colorectal tumours. APC mutation analysis of the MCR showed truncating mutations in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not related to nuclear beta-catenin expression (p=0.75). Rectal cancers showed significantly more nuclear beta-catenin than colon cancers (65% versus 40%, p=0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry (p<0.001). Rectal cancers showed significantly more immunohistochemical expression of p53 than colon cancers (64% versus 29%, p=0.003). In rectal cancers, a significant correlation was found between positive p53 expression and worse disease-free survival (p=0.008), but not in colon cancers. Cox regression showed that p53-expression (p=0.03) was an independent predictor for disease-free survival in rectal cancers. This study concluded that rectal cancer may involve more nuclear beta-catenin in the APC/beta-catenin pathway than colon cancer and/or nuclear beta-catenin may have another role in rectal cancer independently of APC. The p53-pathway seems to be more important in rectal cancer, in which it also has independent prognostic value. When prognostic markers are investigated in larger series, differences in biological behaviour between colon and rectal cancer should be considered., (Copyright 2001 John Wiley & Sons, Ltd.)

Background: Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer. We conducted a multicenter, randomized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision., Methods: We randomly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision (924 patients) or to total mesorectal excision alone (937 patients). The trial was conducted with the use of standardization and quality-control measures to ensure the consistency of the radiotherapy, surgery, and pathological techniques., Results: Of the 1861 patients randomly assigned to one of the two treatment groups, 1805 were eligible to participate. The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone (P=0.84). Among the 1748 patients who underwent a macroscopically complete local resection, the rate of local recurrence at two years was 5.3 percent. The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group (P<0.001)., Conclusions: Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a standardized total mesorectal excision.

The outcome after surgery for rectal cancer differs markedly between patient series regarding local recurrence rates and survival. A high incidence of local recurrence is associated with conventional, nonstandardized procedures. To improve results of surgery, various additional treatments, such as radiotherapy, chemotherapy, and immunotherapy, have been tested. The Swedish Rectal Cancer Trial (SRCT) was the first trial to show that better local control achieved with preoperative radiotherapy resulted in improved survival. In recent years local control and survival have been further improved by the introduction of standardized total mesorectal excision (TME) surgery. A major problem of published studies on adjuvant therapy is that surgery was not standardized in these studies. Furthermore, quality control of the surgical technique by standardized pathological examination of the specimen is absent in most studies. In Europe, TME has become the preferred standard of operative management for rectal cancer. Adjuvant therapy studies should now be reexamined based on a platform of standardized, optimal surgery and pathology. We studied the European trials in which TME surgery is intentionally performed. Most of these trials are still in progress, with follow-up too short for definitive results, apart from interim analyses. However, the Dutch TME trial has already shown that performing a large, multicenter trial with quality control of both surgery and pathology is feasible.

Objective: To document local recurrence in primary rectal cancer when standardised techniques of surgery, radiotherapy, and pathology are used, and to investigate whether the local recurrence rate after total mesorectal excision permits the omission of adjuvant short term preoperative radiotherapy., Design: Prospective randomised study., Setting: Dutch (n = 80), English (n = 1), German (n = 1), Swedish (n = 9), and Swiss (n = 1) hospitals., Subjects: The first 500 randomised Dutch patients with primary rectal cancer., Main Outcome Measures: Local recurrence, survival, operation-related factors, specific pathological tumour characteristics, short and long term morbidity, and quality of life., Results: Between January 1996 and April 1998, 871 Dutch and 94 other patients were randomised. Our feasibility analysis shows that cooperation between and within the participating disciplines goes well. With regard to the surgical part, this can be confirmed by the large number of operations attended by consultant surgeons (58%). The number of abdominoperineal resections appeared to be low (30%), as did the percentage of lateral margins involved (13%). The rate of adverse effects of radiotherapy was acceptable. Apart from a larger operative blood loss and a higher infective complication rate in the irradiated group, no significant differences were found with regard to morbidity and mortality between the randomised groups., Conclusions: The accrual of our trial is going well and it is feasible; short term preoperative radiotherapy is safe even in combination with TME.

Aims: We carried out a population-based study of local recurrence rates in curatively resected patients with rectal cancer, diagnosed between 1988 and 1992. The first objective was to make an inventory of the overall local recurrence rate after non-standardized conventional surgery, inter-institutional recurrence rate variability, and correlations between patient- and tumour-related factors and recurrence rate. A second objective was to investigate the compliance to guidelines for post-operative radiotherapy., Methods: Data were obtained from the Comprehensive Cancer Centre West. The study comprised 1105 patients from 12 hospitals. Of these patients, 437 were ineligible because of missing medical records, no carcinoma, incorrect registration, no laparotomy, non-curative resection, or loss to follow-up., Results: The overall local recurrence rate was 22.5% with a range of 9-36% between the hospitals. These differences were not significant. Dukes' Astler-Coller stage, tumour location, and residual tumour were significant independent prognostic factors for the risk of local recurrence. Indications for post-operative radiotherapy were Dukes' Astler-Coller B2 and C tumours, positive surgical margins, and tumour spill. Compliance to the guidelines for radiotherapy was only 50%. However, no significant difference in recurrence rate was found between patients treated according to the guidelines and those not treated according to the guidelines., Conclusion: This study shows a large variability in local recurrence rate between the participating hospitals and confirms that the risk of recurrence in primary rectal cancer is dependent on Dukes' Astler-Coller stage, tumour location and residual tumour. Furthermore, this study contributes to the discussion about the feasibility of guidelines for post-operative radiotherapy.