Who may omit locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: a failure-pattern-based strategy in the immunotherapy era.

De novo metastatic nasopharyngeal carcinoma (dmNPC) is a heterogeneous disease that exhibits variable failure patterns after first-line immunochemotherapy, complicating the decision-making for subsequent locoregional radiotherapy (LRRT). This retrospective real-world analysis enrolled 398 dmNPC patients treated with first-line immunochemotherapy with or without subsequent LRRT. We developed and validated a clinically applicable two-step risk stratification model that categorizes patients into three phenotypic subgroups based on different failure patterns. Durable responders were defined as patients likely to achieve long-term remission with immunotherapy maintenance alone. Partial responders were prone to experience isolated locoregional progression, while resistant patients had a high risk of developing distant progression, regardless of locoregional control. After inverse probability of treatment weighting adjustment, LRRT significantly improved 2-year progression-free survival (PFS) in partial responders (69.8% vs. 45.1%, HR = 0.45, P < 0.001), but conferred no benefit in durable responders (81.4% vs. 73.4%, P = 0.28) or resistant patients (12.4% vs. 8.6%, P = 0.33). Our findings suggest that only patients prone to isolated locoregional progression may derive survival benefit from LRRT, while others could safely omit LRRT without compromising prognosis. A failure-pattern-based strategy could personalize LRRT decisions and guide future clinical trial design in the immunotherapy era.