With increasing use of low anterior resection, the length of rectum removed below the tumor is often less than the recommended 2 to 5 cm. It is important to know if this decreases the chance of cure. Between 1963 and 1975, 334 patients survived radical restorative operations for single rectal adenocarcinoma. The length of rectum below the tumor measured on fixed pinned-out pathologic specimens was 2 cm or less in 55 patients (group 1), 2 to 5 cm in 177 (group 2), and 5 cm or more in 102 (group 3). The Dukes' classification, histologic grade, and extent of local spread of the tumors were similar in the three groups. Overall crude 5-year survival rates for groups 1, 2, and 3 were 69.1%, 68.4%, and 69.6%, respectively. Corresponding cancer-specific death rates were 25.5%, 23.2%, and 21.6%. These rates were also similar in matching pathologic subgroups of the three main groups. Of 23 observed or suspected local recurrences, there were four recurrences in group 1 (7.3%), 11 in group 2 (6.2%), and eight in group 3 (7.8%). These results suggest that a margin less than 2 cm below a rectal carcinoma does not affect survival or local recurrence adversely.

Background Colorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years. Methods The patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected. Results During the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that. Conclusions This study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies. Electronic supplementary material The online version of this article (10.1186/s12916-019-1379-5) contains supplementary material, which is available to authorized users.

IntroductionIn this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS) and disease free survival (DFS) in colorectal cancer patients from Newfoundland.MethodsThe discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the co-dominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort.ResultsWhen adjusted for sex, age, tumor stage and microsatellite instability (MSI) status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04–2.84, p = 0.036), ERCC5 His46His (HR: 1.78, 95%CI: 1.15–2.76, p = 0.01), SERPINE1 −675indelG (HR: 0.52, 95%CI: 0.32–0.84, p = 0.008), and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03–1.92, p = 0.033). In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18–2.49, p = 0.005), although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort). When stratified based on treatment with 5-Fluorouracil (5-FU)-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04–2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11–2.94, p = 0.018).ConclusionsIn this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two colorectal cancer patient cohorts. Our results also suggest that the MTHFR Glu429Ala polymorphism may be an adverse prognostic marker in patients not treated with 5-FU.

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