Poor response at restaging MRI and high incomplete resection rates of locally advanced mucinous rectal cancer after chemoradiation therapy

Abstract

Aim Mucinous carcinoma is a histological subtype of rectal cancer and has been associated with a poor response to neoadjuvant chemoradiotherapy (CRT). The primary aim of this study was to analyse the response on MRI of mucinous locally advanced rectal cancer (LARC) after CRT compared to regular adenocarcinoma. Method Patients with LARC (defined as cT4 and/or cN2), who underwent CRT followed by restaging MRI and surgery in two tertiary referral hospitals were retrospectively included in the study. Pre‐ and post‐treatment MRI was reviewed by an experienced abdominal radiologist. Results A total of 102 patients, of whom 29 were diagnosed with mucinous carcinoma, were included for analysis. At restaging MRI, adenocarcinoma patients demonstrated significantly less clinical involvement of the mesorectal fascia (37% vs. 62%, P = 0.003) while this was not demonstrated in mucinous carcinoma patients (86% vs. 97%, P = 0.16). Significant downstaging after CRT in adenocarcinoma patients (P = 0.01) was seen while, in mucinous carcinoma patients, no downstaging after CRT (P = 0.89) was seen. Pathology revealed significantly higher rates of an involved circumferential resection margin in mucinous carcinoma versus adenocarcinoma patients (27.6% vs. 1.4%; P < 0.001). After multivariate regression analysis, mucinous carcinoma remained an independent prognostic factor for local recurrence (hazard ratio 3.6; 95% CI 1.1–12.4), although no differences in overall or disease‐free survival were observed. Conclusion Mucinous rectal carcinoma is associated with a poor clinical response at restaging MRI after CRT, leading to relatively higher rates of involved circumferential resection margins at pathology. In this cohort, mucinous carcinoma seems to be a prognostic factor for increased risk of local recurrence, without an effect on overall survival.

Mucinous tumours of the rectum – Call for a change in neoadjuvant strategy

“…Interesting observations were reported in the article on mucinous tumours by Koeter et al, in which poor response to chemoradiation (CRT) and high rate of resections with a positive circumferential margin 1 . We congratulate the authors on supplementing the literature currently available on the unsatisfactory treatment response of mucinous rectal cancers.…”

Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma

“…Compared with common colorectal adenocarcinoma, MCA has entirely distinct clinical, histopathological, and molecular characteristics, as well as an aberrant and aggressive metastatic pattern associated with inadequate response to treatment and worse prognosis 3 . From a clinical perspective, MCA is associated with reduced rates of pathological complete response and tumor downstaging after neoadjuvant chemoradiotherapy compared with non‐mucinous rectal cancer 4,5 . Although immune checkpoint blockade therapy has shown significant efficacy in various solid tumors, MCA patients exhibited a poorer response to PD‐L1 inhibitors than patients lacking the mucinous component 6 .…”

“… 3 From a clinical perspective, MCA is associated with reduced rates of pathological complete response and tumor downstaging after neoadjuvant chemoradiotherapy compared with non‐mucinous rectal cancer. 4 , 5 Although immune checkpoint blockade therapy has shown significant efficacy in various solid tumors, MCA patients exhibited a poorer response to PD‐L1 inhibitors than patients lacking the mucinous component. 6 From a histological and molecular perspective, MCA tumor is characterised by extracellular mucin in more than 50% of the lesion.…”

Reply to Patel et al. ‘Mucinous differentiation of rectal cancers: does it really impact oncological outcomes?’

“…resection rates of locally advanced mucinous rectal cancer after chemoradiation therapy' [1]. In that study we found that mucinous rectal cancer is associated with a poor clinical response at restaging MRI after chemoradiation therapy, leading to higher rates of involved circumferential resection margins (CRMs) at pathology.…”