Elderly Patients with Head-and-Neck Squamous Cell Carcinoma: A Comparison between Surgery and Primary (Chemo)radiation

Purpose/Objective(s) Given the higher frequency of comorbidities and frailty, the optimal management of elderly patients with head-and-neck squamous cell carcinoma (HNSCC) is challenging. As randomized trials comparing surgery versus primary (C)RT for this patient population are difficult to perform, we aimed to compare the oncological outcomes between upfront surgery and definitive (C)RT within a large tertiary cancer center. Materials/Methods Elderly HNSCC patients (≥65 years) without distant metastases treated with upfront surgery or definitive (C)RT between 2010 and 2020 at a tertiary treatment center were included. Patient characteristics and tumor parameters were compared between both treatment groups using t-tests, Fisher's exact tests and chi-square tests. Overall survival (OS) and progression-free survival (PFS) were calculated, and Cox proportional hazard regression analyses of patient- und tumor-related variables were performed to assess the influence of the choice of primary treatment on survival. Results A total of 430 elderly HNSCC patients with a median age of 72 years met the inclusion criteria and were analyzed. Two hundred and seventy-six patients (64.2%) were treated with upfront surgery and risk-adapted adjuvant treatment, and 154 (35.8%) underwent primary (C)RT. Of the 276 patients treated with upfront surgery, 102 patients (37.0%) received adjuvant (C)RT, whereas 174 (63.0%) did not. Incomplete resection occurred in 11 cases (4.0% of the surgery group), while extracapsular spread was present in 33 patients (12.0%). Thirty-five patients (12.7% of the surgery group) received postoperative CRT. Patients receiving primary (C)RT exhibited a worse performance status, were more often smokers and had more often locoregionally advanced tumors (all p<0.001). OS and PFS were superior in patients receiving surgery compared to patients treated by (C)RT (OS: HR=2.696, 95% CI 1.976-3.678, p<0.001, PFS: HR=2.249, 95% CI 1.664-3.040, p<0.001). Age, performance status, comorbidity burden, smoking status, T and N stage and HPV status were prognosticators for OS in the univariate analysis. In the multivariate analysis, choice of primary treatment (OS: HR=1.194, 95% CI 0.563-2.533, p=0.645, PFS: HR=1.112, 95% CI 0.564-2.194, p=0.760) did not constitute a significant parameter for OS or PFS. By restricting analysis to locoregionally advanced tumors (UICC=3-4, n=276), adjuvant (C)RT significantly improved OS compared to surgery alone (median OS: 68 vs. 97 vs. 103 months for surgery vs. surgery+adjuvant RT vs. surgery +postoperative CRT, respectively, p<0.05 for surgery vs. surgery+adjuvant RT, p=0.07 for surgery+postoperative CRT). Conclusion In the multivariate analysis, upfront surgery with risk-adapted adjuvant treatment and primary (C)RT were comparable treatment approaches for elderly HNSCC patients in terms of oncological outcomes. Therefore, elderly HNSCC patients should be informed about both treatment options in order to ensure informed consent.