Meta-analysis of the prognostic value of CpG island methylator phenotype in rectal cancer.

PURPOSE: The pathological and prognostic importance of CpG island methylator phenotype (CIMP) in rectal cancer, as a sub-population of colorectal cancer, is unknown. A meta-analysis was preformed to estimate the prognostic significance of CIMP in rectal cancer. METHODS: A systematic search was performed of PubMed, Embase, MEDLINE, PubMed Central, and Cochrane electronic databases for articles pertaining to CIMP and rectal cancer. Articles were analysed and data extracted according to PRISMA standards. RESULTS: Six studies including 1529 patients were included in the analysis. Following dichotomisation, the prevalence of CIMP-positive tumours was 10 to 57%, with a median of 12.5%. Meta-analysis demonstrated the pooled odds ratio for all-cause death for CIMP-positive tumours vs CIMP-negative tumours was 1.24 (95% CI 0.88-1.74). Z test for overall effect was 1.21 (p = 0.23). Heterogeneity between the studies was low (X2 5.96, df 5, p = 0.31, I2 = 16%). A total of 15 different loci were used for assessing CIMP across the studies, with a median of 6.5 loci (range 5-8). CONCLUSIONS: No significant association between CIMP and poor outcomes in rectal cancer was demonstrated. There was a high degree of heterogeneity in CIMP assessment methodologies and in study populations. Rectal cancer datasets were frequently not extractable from larger colorectal cohorts, limiting analysis.

Locally advanced rectal cancer: management challenges.

Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options.