Margin Status, Lymphovascular Invasion, and Number of Neck Levels Involved Predict Distant Failure in p16+ Oropharyngeal Squamous Cell Carcinoma (OPSCC) Following Transoral Robotic Surgery (TORS)

Abstract

Current management paradigms in p16+ OPSCC are exploring de-intensification strategies due to the generally favorable prognosis of p16+ OPSCC and the high morbidity burden of traditional curative treatment. One of the main concerns with this approach is the heterogeneity within p16+ disease and recognition that there are subpopulations at significant risk of disease failure. Therefore, we sought to examine our own outcomes with p16+ OPSCC to identify pathologic factors associated with significant risk of distant metastasis following TORS. We evaluated 424 consecutive patients who underwent TORS resection for p16+ OPSCC between January 2008 to December 2016 at our institution. Overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were measured from the date of surgery and calculated using the Kaplan-Meier method. The log-rank test was used to compare survival between patient groups. Clinical and pathologic factors associated with DFMS were determined by Cox proportional hazards regression analysis. A two-sided P value of less than 0.05 was considered statistically significant. Median follow-up was 3.4 years (range 1 day – 7.1 years). Median pack-years was 2 years (range, 0 – 100 years). 120 patients (28.3%) received TORS resection alone, 304 patients (71.7%) received post-operative RT, and 143 patients (33.7%) received adjuvant chemoradiation. The majority of patients were Stage IVA (68.6%) and tonsillar cancers (55.0%). Median package time from the date of surgery to the completion of RT was 14.3 weeks. For the entire cohort, 3-year OS was 94.6% (95% CI 92.3% - 97.0%), LRF 89.3% (95% CI 86.1% - 92.5%), and DMFS 94.1% (95% CI 91.7% - 96.5%). On multivariate analysis, lymphovascular invasion (LVI) (HR 2.59, 95%CI 1.09 – 6.16, p = 0.031), margin status (HR 1.91, 95%CI 1.12 – 3.24, p = 0.017) and increased number of neck levels involved (HR 1.75, 95%CI 1.16 – 2.65, p = 0.008) were significantly associated with worse DMFS. Patients with and without LVI had a 3-year DFMS of 87.7% and 96.8% (p = 0.001), respectively. The 3-year DMFS for patients with negative, close, or positive margins was 95.4%, 92.7% and 78.7% (p < 0.001), respectively. Patients with zero, one, two, or three neck levels involved had a 3-year DFMS of 98.5%, 95.6%, 91.6%, and 80.6% (p < 0.001), respectively. This study examines pathologic factors associated with distant relapse in the largest series to date of patients undergoing TORS for p16+ OPSCC. Patients with positive margins, LVI and 3 or more positive neck levels have substantial rates of distant metastasis. These pathologic factors may identify a patient population who may benefit from intensified systemic therapy.