Transoral robotic surgery for human papillomavirus-associated oropharynx squamous cell carcinoma: Recurrence and survival in the Veterans Affairs health system.
Authors: Kumar Abhishek , Cherry Daniel R. , Voora Rohith S. , Faraji Farhoud , Courtney Patrick Travis , Finegersh Andrey , Guo Theresa , Cohen Ezra E.W. , Califano Joseph A. , Mell Loren K. , Rose Brent S. , Orosco Ryan K. 
Published: June 2021

6054

Background: Most transoral robotic surgery (TORS) literature comes from single and multi-institutional studies at tertiary-care academic intuitions. Long-term outcomes for patients with HPV-mediated oropharyngeal squamous cell carcinoma (HPV-OPSCC) treated with upfront TORS in other hospital settings across the United States are largely unknown. We present long-term recurrence and survival outcomes from a novel Veterans Health Administration (VHA) longitudinal dataset that includes patient-level data. Methods: Retrospective analysis of national VHA patients with p16-positive OPSCC diagnosed between January 2010 and December 2016, treated with TORS primary tumor resection with neck dissection. Outcome measures included: Cancer-specific survival (CSS), progression free survival (PFS), overall survival (OS), recurrence, extranodal extension (ENE), positive surgical margin (PSM), and adjuvant therapy regimen. Results: One hundred sixty-one patients were included of whom 29 (18%) were low-risk [0-1 metastatic lymph nodes, negative margins]; 45 (28%) intermediate-risk [close surgical margins, 2 to 4 metastatic nodes, LVI or PNI, pathologic T3 or T4 tumor]; and 87 (54%) high-risk [PSM, ENE, and/or ≥ 5 metastatic nodes]. ENE was present in 41% of cases and 24% of cases had positive surgical margins. Median follow-up was 5.6 years (95% CI 3.0-9.3). The 5-year CSS rates for low, intermediate, and high-risk groups were: 100%, 90.0% (95% CI 75.4-96.1%), and 88.7% (78.3-94.2%). On univariable analysis, pathologic factors associated with inferior CSS were: pT3-T4 tumor category (HR 3.81, 95% CI 1.31-11; p = 0.01), presence of more than four metastatic lymph nodes (HR 3.41, 95% CI 1.20-11; p = 0.02), and ENE (HR 3.53, 95% CI 1.06-12; p = 0.04). Close or PSM were not associated with CSS (HR 0.67, 95% CI 0.21 – 2.14; p = 0.50). In the low-risk group, 48% avoided adjuvant therapy and although there were five recurrences, none died from cancer. The intermediate-risk group was treated with adjuvant radiation in 64% of cases, and chemoradiation in 29% of cases; and there were five locoregional recurrences and three distant recurrences. Adjuvant chemoradiation was used in 68% of high-risk cases. Of the seven total patients with distant recurrences, six died of their disease. Conclusions: Our findings in this national cohort of Veterans with HPV-OPSCC demonstrate that TORS followed by adjuvant therapy yields favorable survival outcomes. Tumor-category, ENE, and more than four nodal metastases were the strongest adverse features in our data, and surgical margins did not have a significant impact on survival. Further investigations with large cohorts and prospective clinical trials are needed to elucidate the true oncologic implications of high-risk features and to identify patients best suited for de-intensified treatment.