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

This retrospective real-world study analyzed 398 patients with de novo metastatic nasopharyngeal carcinoma treated with first-line immunochemotherapy, with or without subsequent locoregional radiotherapy (LRRT). The authors developed and validated a practical two-step risk-stratification model that groups patients into three clinically distinct phenotypes based on expected failure patterns after initial treatment:

• • Durable responders – patients likely to achieve long-term remission on immunotherapy maintenance alone.
• • Partial responders – patients mainly at risk for isolated locoregional progression.
• • Resistant patients – patients with a high likelihood of distant progression regardless of locoregional control.

Using inverse probability of treatment weighting to adjust for baseline differences, LRRT significantly improved 2-year progression-free survival only in the partial responder group (69.8% vs 45.1%; HR 0.45; P < 0.001). There was no meaningful PFS benefit from LRRT in durable responders (81.4% vs 73.4%; P = 0.28) or in resistant patients (12.4% vs 8.6%; P = 0.33).

The study supports a failure-pattern–based approach to personalize LRRT use in this setting: patients predicted to develop isolated locoregional failure appear to benefit from LRRT, while those with durable systemic control or clear systemic resistance may safely omit LRRT without compromising prognosis. This framework may inform both clinical decision-making and future trial design in the immunotherapy era.