Omitting postoperative radiotherapy after pathologic complete response to neoadjuvant immunochemotherapy for patients with locally advanced head and neck squamous cell carcinoma: Survival and patient-reported outcomes.

6105 Background: Neoadjuvant immunochemotherapy (NICT) results in high pathologic response rates in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, whether it is safe to omit postoperative radiotherapy (PORT) for patients who achieved pathologic complete response (pCR) after NICT and surgery remains unclear. We assessed the survival and patient-reported outcomes (PROs) for LA-HNSCC patients who achieved pCR to NICT. Methods: This retrospective cohort study included LA-HNSCC patients who achieved pCR to NICT between July 2019 and June 2025. Patients were categorized into two groups based on whether they received PORT. Propensity score matching (PSM) was performed to minimize confounding and balance baseline characteristics. Kaplan-Meier survival analysis was performed to estimate local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS). EORTC QLQ-C30 and EORTC QLQ-HN35 questionnaires before NICT, preoperatively, and at month 1, 3, and 12 postoperatively were collected. Least-squares mean (LS mean) changes from baseline were estimated using linear mixed-effects models for repeated measures (group, time, and group×time), adjusting for baseline scores. Results: A total of 236 HNSCC patients who achieved pCR after NICT and surgery were included (non-PORT, n = 98; PORT, n = 138). After 1:1 PSM to balance baseline characteristics, 164 patients (82 matched pairs) with comparable baseline characteristics were analyzed. With a median follow-up of 31.67 months (95% CI, 29.57-35.35), survival analysis showed no significant differences between the non-PORT and PORT groups in 2-year LRFS, LRRFS, DMFS or OS (all p > 0.05). Longitudinal EORTC QLQ-C30 global health/QOL analyses showed poorer recovery in the PORT group. PORT was associated with significantly greater postoperative QOL decline at 1 and 3 months postoperatively, with a persistent deficit at 12 months , while non-PORT improved above baseline by 12 months whereas PORT remained slightly reduced. On the EORTC QLQ-HN35, PORT was associated with persistently higher symptom burden, peaking at 3 months postoperatively and remaining elevated up to 1 year compared with non-PORT, suggesting potential QOL benefits of omitting PORT in pCR patients. Conclusions: In this propensity score-matched cohort of LA-HNSCC patients achieving pCR after NICT and surgery, omitting PORT was associated with comparable 2-year disease control and survival but better recovery of multidimensional QOL and lower symptom burden on head and neck-specific PROs. These findings favor omission of PORT for this patient population, while prospective validation and longer follow-up are warranted.