Low prevalence of deficient mismatch repair (dMMR) protein in locally advanced rectal cancers (LARC) and treatment outcomes

Abstract

Background: The available evidence in locally advanced rectal cancer (LARC) suggests a low prevalence of deficient mismatch repair (dMMR) protein status, approximating 1-3%.Methods: Patients with LARC who were offered long course chemoradiation (LCRT), as per institution protocol during the period of 1st January 2014 to 31st December 2015 at Tata Memorial Hospital (TMH) in Mumbai were evaluated for outcomes and assessment of MMR status.Results: A total of 419 patients were evaluated for LARC in TMH, of whom 354 were treated with LCRT.Of these 354 patients, 296 were assessable for MMR status based on tissue adequacy for testing. Three patients (1.01%) has dMMR status, while the remaining 293 patients had proficient MMR status. A total of 240 patients (67.8%) underwent curative intent resections. With a median follow-up of 32 months, estimated 3-year recurrence free survival (RFS) and overall survival (OS) for the resected group was 63.5% and 85.2%, respectively, while 3-year event free survival and OS for the unresected cohort was 15.2% and 15.8%, respectively. Signet ring histology, higher ypT stage, involved margin status post resection, and delays (>1 week) in LCRT were associated with inferior OS on multivariate analysis. Conclusions:In a large LARC cohort, a majority of tumors had proficient MMR status, suggesting that MSI as a biomarker may have limited applicability in the management of rectal cancers. Signet ring histology, CRM involvement post resection, higher ypT stage and interruptions in LCRT predicted for inferior OS.

Complete response in patients with locally advanced rectal cancer after neoadjuvant treatment with nivolumab

“…In LARC, there was about 6% of patients with dMMR or MSI. 3,4 Most of the patients were young. The standard treatment for LARC was fluoropyrimidine with concurrent radiotherapy followed by total mesorectal excision (TME) surgery.…”

Treatment of Metastatic Colorectal Cancers in Resource-Constrained Low- and Middle-Income Countries (LMICS) Scenario—Outcomes, Practice Patterns, and Commentary on Treatment Costs

“…A significant proportion of young patients (< 40 years-32%) and rectal cancers (63.3%) and higher percentage of signet ring cancers (20.3%) were seen in the current cohort and such trends have been shown previously from our institute. 7,8 The presence of an increasing proportion of younger patients having rectal cancer is of significant importance, as there is growing evidence that they likely • mFOLFIRI 85 (21.1)…”

“…A significant proportion of young patients (< 40 years—32%) and rectal cancers (63.3%) and higher percentage of signet ring cancers (20.3%) were seen in the current cohort and such trends have been shown previously from our institute. 7 8 The presence of an increasing proportion of younger patients having rectal cancer is of significant importance, as there is growing evidence that they likely constitute a biologically and clinically distinct cohort, who do not maximally benefit from current treatment paradigm. 9 We have used a cut-off of 40 years in view of the lower median age of the entire cohort.…”

Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting

“…dMMR is found in 15–20% of cases in stage II, 10–15% in stage III, and 4–5% in stage IV colon cancer, 50,51 the prevalence is lower in rectal cancer across all stages (1–10%). 52,53 dMMR is an early event in colorectal carcinogenesis even in sporadic cases and although inter-tumoral heterogeneity of MMR status has been a subject of debate, discordance between primary tumor and metastases seems extremely rare. 54 dMMR CRC is enriched with mutations in RAS , BRAF, HER2 , and NTRK fusions; all are considered mutually exclusive.…”