Limited Benefit of Postoperative Chemoradiotherapy in Intermediate-Risk Locally Advanced Head and Neck Squamous Cell Carcinoma: Real-World Evidence from the IMRT Era

Background In the era of intensity-modulated radiotherapy (IMRT), the benefit of adding concurrent chemotherapy to postoperative radiotherapy (PORT) for intermediate-risk locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without positive margins (R1) or extracapsular extension (ECE) remains controversial. Methods We retrospectively analyzed patients with intermediate-risk LA-HNSCC treated with postoperative chemoradiotherapy (POCRT) or PORT at our institution. Propensity score matching (PSM) was performed to balance baseline characteristics. Independent prognostic factors were identified through Cox regression analysis, and survival outcomes were compared between groups. Results After matching, 131 patients were included (39 POCRT, 92 PORT). Perineural Invasion (PNI) was an independent adverse factor for progression-free survival (PFS; HR 3.07,95% CI 1.46–6.69, P = 0.005), locoregional recurrence-free survival (LRRFS; HR 3.86, 95% CI 1.41–10.60, P = 0.009), and distant metastasis-free survival (DMFS; HR 5.76, 95% CI 1.09–30.59, P = 0.04). Lymphovascular invasion (LVI) was independently associated with worse overall survival (OS; HR 6.83, 95%CI 1.60–29.05, P = 0.009) and PFS (HR 4.02, 95%CI 1.21–13.37, P = 0.023). POCRT did not significantly improve OS, PFS, LRRFS, or DMFS compared to PORT. Conclusions In intermediate-risk LA-HNSCC patients treated with IMRT, PNI and LVI were key prognostic indicators, while POCRT conferred no survival advantage over PORT. These findings suggest the need for prospective validation before the routine use of POCRT in this subgroup.