It remains uncertain whether induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) or CCRT plus adjuvant chemotherapy (AC) is more effective in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This study aimed to develop and validate a joint radiomic and clinical signature (RCS) for the prognostic stratification of LA-NPCs and to identify patients who might benefit more from IC + CCRT or CCRT + AC.Overall, 893 LA-NPC patients who received IC + CCRT or CCRT + AC were enrolled from four hospitals. RCS based on pretreatment magnetic resonance images and clinical data was constructed for predicting 5-year progression-free survival (PFS). The predictive ability of the RCS and TNM staging system for 5-year PFS, locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were compared by Harrell's concordance indices (C-indices). Patients were divided into high- and low-risk subgroups based on RCS scores. The survival benefit of IC + CCRT vs. CCRT + AC in different subgroups was compared by Kaplan-Meier survival curves.The RCS combining the radiomic signature, TNM stage and EBV DNA demonstrated significantly higher C-indices than TNM stage for predicting 5-year PFS, LRRFS, DMFS and OS in the training and validation cohorts. In the high-risk group (RCS score ≥ 0.25), CCRT + AC achieved significantly better PFS, LRRFS, DMFS and OS than IC + CCRT. In the low-risk group (RCS score < 0.25), IC + CCRT yielded significantly better outcomes than CCRT + AC.The RCS provides a noninvasive way to predict the outcomes of LA-NPC and helps identify patients who may benefit more from IC + CCRT vs. CCRT + AC.Copyright © 2022 Elsevier B.V. All rights reserved.