Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Cancer.

Importance: Distant metastasis (DM) remains the leading cause of death in patients treated for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). An effective treatment strategy needs to address DM while reducing treatment-related toxic effects.

Objective: To assess DM-free survival in patients with HPV-OPSCC treated with neoadjuvant chemotherapy followed by transoral robotic surgery (NECTORS) and neck dissection compared with standard of care, concurrent chemoradiation (CCRT).

Design, Setting, And Participants: This multicenter retrospective cohort study compares prospective data from the NECTORS treatment group with a historical cohort of patients treated with CCRT. Patients with American Joint Committee on Cancer seventh edition stage III and IVa HPV-OPSCC treated with NECTORS and CCRT between February 2010 and September 2021 were included. Data were analyzed in September 2024.

Exposures: Patients in the NECTORS arm were treated with 3 cycles of neoadjuvant docetaxel and cisplatin followed by TORS and neck dissection. Patients in the radiation therapy arm were treated with concurrent high-dose cisplatin and radiotherapy.

Main Outcomes And Measures: DM-free survival was analyzed with Kaplan-Meier and Cox regression after adjusting for age, sex, tobacco and alcohol use, site, and cancer stage.

Results: Of 342 included patients, 282 (82.5%) were male, and the mean (SD) age was 61.4 (9.4) years. A total of 232 patients were treated with CCRT and 110 patients were treated with NECTORS. Within the CCRT arm, 11 patients (4.7%) had locoregional recurrence (LRR), 5 (2.2%) had LRR and DM, and 28 (12.1%) developed distant-only metastasis. For patients treated with NECTORS, 5 (4.5%) developed LRR, 1 (0.9%) developed LRR plus DM, and no patients developed distant-only metastasis. With pseudorandomization matching for T and N stages, 209 patients were matched between the 2 treatment groups for further analysis (105 in the CCRT treatment arm and 104 in the NECTORS arm). The median (range) follow-up period for the CCRT and NECTORS groups were 5.8 (3.8-7.5) years and 5.1 (4.0-5.9) years, respectively. The hazard ratio of developing distant recurrence in the CCRT group was 10.77 (95% CI, 1.40-82.90) in univariate analysis and 9.98 (95% CI, 1.29-77.29) in multivariable analysis. In Kaplan-Meier survival analysis, the risk of developing DM was higher in the CCRT group. The hazard ratio for failure anywhere in the CCRT group was 3.32 (95% CI, 1.23-8.97) in univariate analysis and 3.21 (95% CI, 1.18-8.72) in multivariable analysis.

Conclusions And Relevance: In this study, neoadjuvant chemotherapy followed by transoral robotic surgery and neck dissection was an effective treatment option for patients with stage III and IVa HPV-OPSCC. Findings from our study suggest lower rates of DM with NECTORS worthy of further investigation in prospective randomized trials.