Impact of age on the prognosis and decision-making of adjuvant treatment for resectable rectal cancer- a population based analysis

Abstract Background Different age groups exhibit disparate patterns of epidemiology, clinicopathology, treatment response, and prognosis in relation to rectal cancer (RC), but little is known about the interactions between age and adjuvant treatment (AT) for resectable RC. Methods The Surveillance, Epidemiology, and End Results database (SEER) was used to identify patients who had received surgery but not neoadjuvant treatment for rectal adenocarcinoma between 2010 and 2015. Restricted cubic spline (RCS) was used to identify the optimal cut-off value of age for overall survival (OS) and cancer-specific survival (CSS), and then further analysis was performed using Kaplan-Meier (KM) curves and propensity score matching (PSM) stratified by different age groups, pathological stage (pT1 − 2N0, pT3 − 4N0, pT1 − 4N+), and AT modalities including chemotherapy (CT), radiotherapy (RT), and CT + RT. Results 7951 patients were eligible for this study, and age was found to be an independent risk factor of OS and CSS after adjusted other risk factors (all P < 0.001). 50 years old was identified as the optimal cut-off value for OS and CSS using RCS, and patients aged < 50 years old (early-onset rectal cancer, EORC) have a significantly better prognosis than those aged ≥ 50 years old (late-onset rectal cancer, LORC) before and after PSM (both P < 0.001). Among the EORC patients, only subgroup of pT1 − 4N + was found to be benefited from AT before and after PSM (both P < 0.05), and further analysis showed that this population was only benefited from adjuvant CT in terms of OS (P < 0.05). Among LORC patients, subgroups of pT3 − 4N0 and pT1 − 4N + were both found to be benefited from AT (both P < 0.001). Further analysis showed that adjuvant CT and CT + RT could both significantly improve the OS of these two subgroups (all P < 0.05), but adjuvant RT alone was only found to benefit those staged at pT1 − 4N+ (P < 0.05). Conclusions The optimal age threshold for RC patients undergoing direct surgery was 50 years old. Patients with EORC staging at pT1-4N + should receive adjuvant CT + RT. Patients with LORC staging at pT3-4N0 and pT1-4N + should receive adjuvant CT + RT or CT. In addition, adjuvant RT alone could also be an option for selected LORC patients. However, this conclusion deserves further validation by prospective cohorts.