Association of age and primary treatment with risk of non-lymphoma-related death and long-term survival outcomes in adult patients with early-stage follicular lymphoma: a population-based analysis

Abstract

In adult patients with early-stage follicular lymphoma (FL), age-related differences in the risk of non-lymphoma-related death (LRD) during the follow-up period after treatment are unclear. We aimed to investigate the interactive effects of age and primary treatment on the risk of non-LRD and survival. We retrospectively analyzed the data of 6030 adult patients with early-stage FL from the Surveillance, Epidemiology, and End Results (SEER) database (2000–2020). Primary therapy involved observation (n = 2509), chemotherapy (CT) alone (n = 1844), radiotherapy alone (RT, n = 1191) or RT and CT (RT + CT, n = 486). The groups were balanced by inverse probability of treatment weighting (IPTW). Comparisons of the cumulative incidence of non-LRD were performed using competing-risk analysis and transformed Cox regression analysis. The median patient age was 64 years (RT, 62 years; RT + CT, 60 years; CT, 63 years; observation, 66 years). Over a median follow-up period of 132 months, 830 patients (13.8%) died of FL, while non-LRD accounted for 1279 patients (21.2%). Age significantly influenced the non-LRD risk, especially in patients aged > 60 years. After IPTW adjustment, RT alone, RT + CT or CT alone was not associated with an increased risk of the cumulative incidences of non-LRD or its specific causes in comparison with observation. Age-dependent analyses showed that the adjusted hazard ratios (HRs) for RT alone, RT + CT or CT versus observation remained close to 1.0 across the age spectrum, indicating no significant difference in non-LRD risk between treatment groups. RT alone and RT + CT conferred sustained overall survival (OS), disease specific survival (DSS) and relative survival (RS) advantages over CT or observation, with RS consistently exceeding 90% over the extended follow-up period. The survival benefit of RT versus non-RT persisted across age groups, with the adjusted HRs for OS and RS remaining below 1.0 for most ages. Older age, not primary treatment, was associated with an increased risk of non-LRD. The results indicated the safety and long-term survival benefit of RT in adult patients with early-stage FL.