Predictors of pathological complete response after total neoadjuvant treatment using short course radiotherapy for locally advanced rectal cancer.

Abstract

Background: Total neoadjuvant treatment (TNT) has become a standard treatment approach for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following TNT have better outcomes (overall survival, relapse free survival). However, not all patients treated for LARC with neoadjuvant treatment achieve pCR.

Aim: The aim of our study was to assess the rate and predictors of pCR.

Materials and methods: We performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive LARC patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and January 2023 were included in the research. Pathological response to neoadjuvant treatment was assessed using Mandard grading system and response was categorized as pCR or not‑pCR. Two different standardized protocols for the neoadjuvant treatment were used: the first group was treated with induction chemotherapy followed by short course radiotherapy and the second group was treated with the RAPIDO protocol. Correlation between different studied parameters and pCR was determined using univariate and multivariate logistic regression analysis.

Results: The mean age of the 91 included patients (46 men and 45 women) was 58.53 ± 10.3 years. Twenty (22%) were found to have a pCR (Mandard TRG1) in the operative specimen. In univariate analysis, patients less than 60 years, continuation of chemotherapy and patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p = 0.043, p = 0.0001 and p = 0.021 respectively). Patients with mucinous component had low pCR rates (p = 0.021). On logistic regression analysis, chemotherapy continuation (OR = 10.27, 95% CI = 2,14-49.32), and absence of mucinous component (OR = 12.6, 95% CI = 3.1-40.32) were significant predictors of pCR. The median survival was 37.7 months.

Conclusion: Mucinous component and chemotherapy interruption are associated with lower pCR rates. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve outcomes for patients with LARC.