Sadeghi Nader, Subramaniam Thavakumar, Richardson Keith, Mascarella Marco, Zeitouni Anthony, Shenouda George, Sultanem Khalil, Mlynarek Alex, Caglar Derin, Esfahani Khashayar, Joshi Arjun, Siegel Robert, Goodman Joseph, Thakkar Punam, Lee Esther, Golabi Nahid, Ramanakumar Agnihotram V, Hier Michael, Bouganim Nathaniel
Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada.
Department of Oncology, McGill University, Montreal, Quebec, Canada.
JAMA Otolaryngol Head Neck Surg. 2025 Feb 1;151(2):128-134. doi: 10.1001/jamaoto.2024.3303.
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.
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.
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.
DM-free survival was analyzed with Kaplan-Meier and Cox regression after adjusting for age, sex, tobacco and alcohol use, site, and cancer stage.
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.
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.
远处转移（DM）仍然是接受人乳头瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）治疗患者的主要死亡原因。一种有效的治疗策略需要在解决远处转移问题的同时减少治疗相关的毒性作用。
评估接受新辅助化疗后经口机器人手术（NECTORS）及颈部清扫术的HPV-OPSCC患者与标准治疗方案同步放化疗（CCRT）相比的无远处转移生存期。
设计、地点和参与者：这项多中心回顾性队列研究将NECTORS治疗组的前瞻性数据与接受CCRT治疗的历史队列患者的数据进行比较。纳入2010年2月至2021年9月间接受NECTORS和CCRT治疗的美国癌症联合委员会第七版III期和IVa期HPV-OPSCC患者。2024年9月对数据进行分析。
NECTORS组患者接受3个周期的新辅助多西他赛和顺铂治疗，随后进行经口机器人手术（TORS）及颈部清扫术。放疗组患者接受同步高剂量顺铂和放疗。
在对年龄、性别、烟草和酒精使用情况、部位及癌症分期进行调整后，采用Kaplan-Meier法和Cox回归分析无远处转移生存期。
在纳入的342例患者中，282例（82.5%）为男性，平均（标准差）年龄为61.4（9.4）岁。共有232例患者接受CCRT治疗，110例患者接受NECTORS治疗。在CCRT组中，11例（4.7%）发生局部区域复发（LRR），5例（2.2%）发生LRR和DM，28例（12.1%）仅发生远处转移。接受NECTORS治疗的患者中，5例（4.5%）发生LRR，1例（0.9%）发生LRR加DM，无患者仅发生远处转移。通过对T和N分期进行伪随机匹配，在两个治疗组之间匹配了209例患者进行进一步分析（CCRT治疗组105例，NECTORS组104例）。CCRT组和NECTORS组的中位（范围）随访期分别为5.8（3.8 - 7.5）年和5.1（4.0 - 5.9）年。单因素分析中，CCRT组发生远处复发的风险比为10.77（95%CI，1.40 - 82.90），多因素分析中为9.98（95%CI，1.29 - 77.29）。在Kaplan-Meier生存分析中，CCRT组发生DM的风险更高。CCRT组在任何部位失败的风险比在单因素分析中为3.32（95%CI，1.23 - 8.97），多因素分析中为3.21（95%CI，1.18 - 8.72）。
在本研究中，新辅助化疗后经口机器人手术及颈部清扫术是III期和IVa期HPV-OPSCC患者的一种有效治疗选择。我们研究的结果表明NECTORS组的远处转移率较低，值得在前瞻性随机试验中进一步研究。
