Patterns of recurrence and outcomes of poor responders to neoadjuvant long-course chemoradiotherapy for rectal cancer

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery and adjuvant chemotherapy is a standard therapy for locally advanced rectal cancer (LARC). However, a significant proportion of patients exhibit a poor response, and few studies focus on this subgroup's prognosis. The aim of this study was to investigate the prognosis of locally advanced rectal cancer patients with poor response to neoadjuvant chemoradiotherapy.

Between July 2013 and August 2023, we retrospectively collected data from patients with LARC who received long-course nCRT and surgery at our hospital. Patients with tumor regression grade 3 were defined as poor responders, and their recurrence patterns, long-term oncological outcomes were analyzed.

A total of 135 patients were included in the analysis, with a median follow-up duration of 45 months. Recurrence occurred in 65 patients, with the following recurrence patterns: locoregional recurrence (n=12), lung metastasis (n=19), liver metastasis (n=8), metastases to other sites (n=3), multiple-site recurrence (n=13) and unknown site (n=10). The 5-year overall survival and 3-year disease-free survival were 56.8% and 53.1%, respectively. Despite poor response to nCRT, adjuvant chemotherapy emerged as an independent protective factor for overall survival [hazard ratio (HR) =0.415, 95% confidence interval (CI): 0.185-0.930, P=0.03].

Poor responders to nCRT in LARC have high risk of recurrence and metastasis, especially lung metastasis. Adjuvant chemotherapy could improve the overall survival in this group.