Neoadjuvant radiotherapy improves overall survival for T3/4N+M0 rectal cancer patients: a population-based study of 20300 patients

BACKGROUND: Neoadjuvant radiotherapy (RT) has been shown to improve local control; however, whether it can improve overall survival (OS) in locally advanced rectal cancer (LARC) patients remains controversial. We therefore aimed to examine the benefits of surgery alone, neoadjuvant radiotherapy (RT), adjuvant RT, and surgery plus chemotherapy in stage II (T3/4N0M0) and III (any T and N + M0) on the OS of rectal cancer patients. METHODS: Date from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2004 and 2016 were used. Kaplan-Meier analyses were used to compare patient prognoses across different treatment modalities. Cox hazard regression analysis were used to identify independent predictors of OS. RESULTS: For stage T3/4N0M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p > 0.05; mean survival, 115.89 months (M), 111.97 M, and 117.22 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival, 88.96 M). For stage T1/2N + M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p > 0.05; mean survival, 121.50 M, 124.25 M, and 121.20 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival 83.81 M). For stage T3/4N + M0 patients, neoadjuvant RT (HR = 0.436; 95% CI, 0.396~0.478; p < 0.001) resulted in significantly longer OS than adjuvant RT and surgery plus chemotherapy (mean survival, 104.47 M, 93.94 M, and 93.62 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival 54.87 M). Older age (> 60 years), black race, unmarried status, high tumour grade, and tumour size > 5 cm were all associated with a poor prognosis (all p < 0.05). CONCLUSIONS: Neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy results in better OS than surgery alone in LARC patients. Neoadjuvant RT has the potential to be highly recommended over adjuvant RT and surgery plus chemotherapy for T3/4N + M0 patients; however, it showed no OS advantage over adjuvant RT or surgery plus chemotherapy for T3/4N0M0 and T1/2N + M0 patients.