Complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer and systemic oncologic benefit: a retrospective cohort study in Korea

Neoadjuvant chemoradiotherapy (CRT) improves local control in locally advanced rectal cancer (LARC) but has not consistently demonstrated a survival benefit. This study evaluated whether pathological complete response (ypCR) after CRT confers systemic oncological benefit beyond local tumor control.

A total of 1,105 patients with clinically staged T3 or node-positive rectal cancer who underwent total mesorectal excision at a single tertiary center between 2004 and 2019 were categorized into 3 groups: no CRT (n=608), non-ypCR (n=414), and ypCR (n=83). Primary outcomes were 5-year overall survival (OS) and relapse-free survival (RFS). Secondary outcomes were 5-year cumulative incidences of local recurrence and distant metastasis.

Five-year OS rates were 77.6%, 82.0%, and 95.7% in the no-CRT, non-ypCR, and ypCR groups, respectively. The ypCR group demonstrated superior OS compared with both no-CRT and non-ypCR groups (P=0.001 and P=0.007, respectively). The marginal OS difference between the no-CRT and non-ypCR groups (P=0.047) was no longer significant after multivariable adjustment (hazard ratio, 0.903; P=0.622). Five-year RFS rates were 69.6%, 72.5%, and 91.1% in the no-CRT, non-ypCR, and ypCR groups, respectively. The 5-year cumulative incidence of distant metastasis was lower in the ypCR group (7.5%) than in the no-CRT and non-ypCR groups (23.8% and 25.0%, respectively; P=0.005). On multivariable analysis, ypCR remained independently associated with reduced risks of death, relapse, and distant metastasis.

The ypCR after neoadjuvant CRT in LARC was associated with superior survival and reduced distant metastasis, suggesting effective systemic tumor control rather than a local treatment effect alone.