Adjuvant Oropharynx Cancer Management in the Era of Tors and HPV: A Recursive Partitioning Analysis

Abstract

<h3>Purpose/Objective(s)</h3> The excellent prognosis of human papillomavirus (HPV)-associated oropharynx cancer (OPC) has raised concern about overtreatment and underlies ongoing efforts to reduce morbidity. However, consensus guidelines continue to advocate risk-stratified management that predates the recognition of HPV+ OPC as a distinct entity. This study aims to identify pathologic risk factors following Transoral Robotic Surgery (TORS) that are prognostic for survival and predictive of benefit from adjuvant therapies. <h3>Materials/Methods</h3> In the 2017 National Cancer Database, there were 2,473 patients with OPC undergoing upfront TORS with ≥90 days of follow up, complete data on pathologic factors (pT, pN, HPV, number of positive lymph nodes (LN), lymphovascular invasion, and extracapsular extension [ECE]), and complete data on adjuvant therapy. Three adjuvant approaches were evaluated: no adjuvant therapy (NaT), adjuvant radiotherapy (aRT), and adjuvant chemoradiotherapy (aCRT). Recursive partitioning analysis (RPA) was performed to sort patients into prognostic groups. Logrank test was used to compare overall survival (OS) between groups. Multiple correction for pairwise comparisons was performed using an FDR approach. Within groups, both logrank and Cox regression were used to compare OS between adjuvant approaches. <h3>Results</h3> RPA identified four prognostic groups. Group I (HPV+ and pT0-1, n=964) and Group II (HPV+, pT2-4, ECE-, n=772) had significantly better survival than Group III (HPV+, pT2-4, ECE+, n=346) or Group IV (HPV-, n=391). There was no significant OS difference within Groups I or II between NaT and either aRT or aCRT (<b>Table</b>). Within Group III, OS was significantly improved with aRT or aCRT compared to NaT but did not significantly differ between aRT and aCRT (pairwise <i>p</i>=0.73). In Group IV there was no statistically significant OS difference between NaT and either aRT or aCRT. <h3>Conclusion</h3> Consistent with the RPA derived from the organ preservation setting, HPV status persists as the strongest prognostic factor for OPC patients undergoing TORS. ECE emerged as the second strongest factor, but nodal disease burden was not selected as a prognostic variable. The addition of adjuvant therapy was associated with the greatest improvement in OS among patients with HPV+, pT2-4, ECE+ OPC. Patients with HPV- OPC suffered the worst OS even with adjuvant therapy, underscoring the unmet need for novel treatment approaches in this population.