Association of Pathological Complete Response with Long-Term Oncological Outcomes After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Retrospective Analysis of 327 Patients.

Background and Objectives: While total neoadjuvant therapy (TNT) is increasingly adopted, conventionally fractionated neoadjuvant chemoradiotherapy (CRT) followed by surgery remains the standard approach for many patients with locally advanced rectal cancer (LARC). Tumor regression following neoadjuvant therapy varies, potentially influencing oncologic outcomes. This study aimed to evaluate the association between pathological complete response (pCR) and long-term overall survival (OS) and disease-free survival (DFS) in patients with LARC undergoing neoadjuvant therapy and surgery. Materials and Methods: This retrospective study included patients who received long-course radiotherapy with concurrent capecitabine, followed by curative-intent surgery between January 2006 and January 2017. Patients were stratified according to the presence or absence of pCR. The primary outcomes were 5-year OS and DFS; secondary outcomes included locoregional recurrence and distant metastasis rates. Results: Among 327 patients, 47 (14.4%) achieved pCR. Patients with pCR had significantly lower pretreatment clinical T stage (p = 0.033) and clinical N stage (p = 0.049) and were more frequently classified as clinical stage II (55.3% vs. 40.0%, p = 0.049). Long-term oncological analyses included 322 patients after the exclusion of five early postoperative deaths. Locoregional recurrence (6.4% vs. 9.8%, p = 0.59) and distant metastasis (10.6% vs. 20.0%, p = 0.15) were numerically less frequent in the pCR group but did not differ significantly. Five-year OS was 91.5% in the pCR group and 73.1% in the non-pCR group (log-rank p = 0.027), while 5-year DFS was 85.1% and 61.5%, respectively (log-rank p = 0.008). After adjustment for age, sex, tumor location, pretreatment clinical T and N stage, and the CRT-to-surgery interval, pCR remained associated with improved DFS (adjusted HR 0.542, 95% CI 0.296-0.994, p = 0.048). In contrast, the association between pCR and OS was attenuated and did not reach statistical significance (adjusted HR 0.575, 95% CI 0.305-1.083, p = 0.087). Conclusion: pCR following neoadjuvant therapy in patients with LARC is associated with favorable long-term oncological outcomes. After adjustment for baseline clinical characteristics, pCR remained associated with improved DFS, whereas its association with OS was attenuated and did not reach statistical significance. These findings support the prognostic relevance of pCR while emphasizing the contribution of baseline disease characteristics to long-term survival.