The Effect of Tumor Margin Status on Progression-Free Survival (PFS) in Patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC) after Transoral Robotic Surgery (TORS)

Abstract

<h3>Purpose/Objective(s)</h3> Human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPSCC) has an excellent prognosis, and many patients are treated with transoral robotic surgery (TORS). It is unclear if adjuvant therapy post-TORS in the HPV-positive population should be guided by the same criteria as HPV-negative OPSCC. We sought to examine post-TORS outcomes from a single institution. <h3>Materials/Methods</h3> From a prospectively collected single institution database of head/neck cancer patients, we retrospectively identified patients with OPSCC who underwent TORS from 2015-2021. Demographic, clinical, and pathologic information including margin status and distance from tumor were assessed. Patients were stratified by tumor margin status (positive and negative tumor margin status). Progression-free survival (PFS) probabilities were estimated using the Kaplan-Meier method. Distributions were compared between groups using the log-rank test statistic. <h3>Results</h3> 163 patients who underwent TORS were selected (152 with HPV-positive tumors) with a median age of 59 years (range, 31-79). Most patients had tonsil primaries (115, 70.6%) and T1-2 disease (T1 72 (44.2%), T2 77 (47.2%)). 131 had negative surgical margins (-SM), 32 had positive surgical margins (+SM). There was no significant difference between the two groups. Median distance from negative tumor margin was 0.5mm (range, 0.5-5). PFS analyses were adjusted for HPV-status and pathological features including PNI and LVI. 2yr PFS for -SM was 98.4% vs 93.8% for +SM (p < 0.005). Outcomes for patients with -SM by adjuvant therapy were (n, 2yr PFS): observation (23, 95.2%), radiation (65, 95.3%), chemoradiation (43, 92.9%, p < 0.005). Outcomes for patients with +SM by adjuvant therapy were (n, 2yr PFS): observation (3 patients declined adjuvant therapy, 66.7%), radiation (8 patients declined concurrent chemotherapy, 94.6%), chemoradiation (21, 91.3%, p < 0.005, limited by majority of patients receiving adjuvant chemoradiation). When examining by tumor margin distance and impact on PFS, each additional millimeter resected from tumor defining -SM increased 2yr PFS by 24.3% starting from 0.5mm until 2.4mm. <h3>Conclusion</h3> +SM post-TORS in a largely HPV-positive population from a single institution portends worse 2yr PFS, with a decrement of approximately 5%. In -SM patients, distance from tumor to margin impacted PFS up to 2.4mm, confirming ECOG 3311 cutoff of 3mm as defining close margins. Thus, +SM and close margins continue to impact outcomes in this good risk-population with early-stage HPV-positive cancer and should inform adjuvant therapy recommendations. Ongoing prospective studies investigating de-escalation of adjuvant therapy post-TORS represent cautious efforts to identify means to reduce toxicity in this population.