Presence and clinical significance of acellular mucin pools in resected rectal cancer with pathological complete response after pre‐operative chemoradiotherapy

For patients with locally advanced rectal cancer (LARC), a pathological complete response (pCR) after pre-operative chemoradiotherapy (CRT) does not necessarily indicate a cure. Acellular mucin pools are often seen in patients with pCR. However, the clinical significance of acellular mucin pools in this group of patients remains unknown. This was a retrospective analysis of 225 LARC patients who achieved pCR following CRT and total mesorectal resection from 2011 to 2018. The outcomes of 5-year disease-free survival (DFS), 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) were compared in patients with versus without acellular mucin pools. Among 225 pCR patients, acellular mucin pools could be identified in 56 (24.9%) patients, and recurrence occurred in 30 (13.3%) patients at 5 years. Distant recurrence was seen in 13 (23.2%) patients with acellular mucin pools and in 17 (10.1%) patients without acellular mucin pools. Patients with acellular mucin pools versus those without had poorer DFS (76.8 versus 89.9%, P = 0.010) and OS (87.5 versus 97.0%, P = 0.004) at 5 years. The presence of acellular mucin pools was the independent parameter that remained significant for DFS [hazard ratio (HR) = 3.904; 95% confidence interval (CI) = 1.342-11.356; P = 0.047] and OS (HR = 3.850; 95% CI = 1.214-12.213; P = 0.022) on multivariate analysis. A total of 17 patients demonstrated acellular mucin pools in primary tumour and lymph nodes. Subgroup analysis demonstrated that pCR patients with acellular mucin pools in primary tumour and lymph nodes were more likely to develop distant metastasis compared to pCR patients with acellular mucin pools only in primary tumour (47.1 versus 12.8%, P = 0.005). In summary, acellular mucin pools in LARC patients with pCR after CRT might represent a sign of invasive tumour biology and significantly shorten the prognosis of patients, especially in patients with acellular mucin pools in lymph nodes.