Survival outcomes and pathologic complete response following neoadjuvant chemoradiotherapy versus chemotherapy alone in locally advanced rectal cancer

Background

The management of locally advanced rectal cancer (LARC) continues to evolve, marked by significant advancements in treatment paradigms. Total neoadjuvant therapy (TNT) has emerged as a promising strategy, while de-escalation approaches, such as neoadjuvant chemotherapy (nCT) alone, are gaining traction to mitigate radiation-related toxicities without compromising oncologic efficacy. This study aimed to compare survival outcomes and pathologic complete response (pCR) rates between patients with LARC treated with neoadjuvant chemoradiotherapy (nCRT) and those treated with nCT alone.

Methods

This retrospective cohort study analyzed data from the National Cancer Database (NCDB) between 2015 and 2019. The inclusion criteria were non-metastatic clinical T2 node-positive, T3 node-negative, and T3 node-positive rectal adenocarcinoma patients undergoing partial proctectomy with neoadjuvant therapy. The stabilized inverse probability of treatment weighting (IPTW) was applied to balance the baseline characteristics. Overall survival was assessed using Kaplan-Meier curves and multivariable Cox proportional hazards models, while pCR rates were analyzed using logistic regression.

Results

Of 6886 patients included, 386 (5.6 %) received nCT alone, and 6500 (94.4 %) received nCRT. After IPTW adjustment, no significant difference in overall survival was observed between nCRT and nCT alone groups (HR: 0.99, 95 % CI: 0.69–1.41, p = 0.936). pCR rates were similar (OR: 1.20, 95 % CI: 0.77–1.98, p = 0.438). Subgroup analysis revealed non-significant trends toward higher pCR rates with nCRT in T3 node-positive patients (OR: 1.44, 95 % CI: 0.77–3.05, p = 0.297). Residual tumor margins (HR: 3.04, 95 % CI: 2.34–3.94, p < 0.001) and incomplete pathological response (HR: 1.68, 95 % CI: 1.22–2.31, p = 0.002) were significant predictors of worse survival outcomes regardless of treatment modality.

Conclusion

This large-scale analysis demonstrates comparable overall survival and pCR rates between nCRT and nCT alone in carefully selected with LARC patients, supporting the growing evidence for selective radiation omission strategies. These findings align with those of contemporary de-escalation trials and suggest that nCT alone may be a viable treatment option for specific patient subgroups. Future prospective studies incorporating quality of life assessments and long-term functional outcomes are essential to optimize personalized treatment strategies and refine patient selection criteria for radiation de-escalation in LARC management.