Transoral robotic surgery (TORS) and de-escalated adjuvant therapy for human papillomavirus-related oropharyngeal carcinoma (HPVOPC): Long-term follow up of the Sinai Robotic Surgery (SIRS) trial (NCT02072148).

Abstract

6089 Background: De-escalation therapy for HPVOPC remains undefined and controversial. Definitive and postoperative chemoradiation are associated with significant toxicity. Efforts to de-intensify treatment with CRT only, such as HN002 and HN005, were unsuccessful. A previous investigation by this group (SIRS 1.0) and E3311 have highlighted the potential value of TORS with pathological risk stratification of patients for de-escalated adjuvant therapy. Our early work demonstrated that TORS, in combination with reduced-dosed adjuvant therapy for early and intermediate HPVOPC, resulted in equivalent progression-free survival (PFS) and overall survival (OS) while reducing toxicity in the first two years of treatment. Here we report the 5-year results for SIRS. Methods: This is a nonrandomized phase II trial for early-stage molecularly confirmed HPVOPC patients (n=63) treated with TORS followed by reduced-dose adjuvant therapy based on pathological risk-stratification into one of three groups: Group 1 (n=31) with no adjuvant therapy, Group 2 (n=15) with 50-Gy radiotherapy, and Group 3 (n=17) with 56-Gy chemoradiotherapy concurrent with weekly cisplatin. Patient demographics, baseline tumor characteristics, clinical outcomes, and adverse events during treatment and surveillance were recorded across the full 5-year study period. Results: Among the 63 total patients, median follow-up is 58 months (IQR 43—76 months). In the first two years following TORS, 5 patients experienced locoregional recurrence (7.9%); of these, one later had distant metastasis and one had a second HPV+ recurrence in the ipsilateral neck. All were salvaged by TORS, neck dissection, and/or chemoradiation. No patients had an HPVOPC recurrence between years 2 to 5 of follow-up. Two patients, one each from Group 1 and Group 2, developed a molecularly proven HPV+ contralateral second primary tumor at the tonsils approximately 5 years following TORS. Both patients were successfully salvaged and remain disease-free. Two patients (one each in Group 2 and 3) died from causes unrelated to cancer. The five-year OS is 96.8% (61/63) and the disease-specific survival (DSS) is 100% (63/63). Five-year PFS is 87.1% (27/31) for Group 1, 86.7% (13/15) for Group 2, 94.1% (16/17) for Group 3, and 88.9% (56/63) for the full cohort. Conclusions: Long-term follow-up of SIRS demonstrates de-escalation TORS and pathologic risk stratification is safe and effective in molecularly proven HPVOPC and reduces the lethal and morbid long-term side effects of full dose radiation and CRT. All recurrences occurred in the first two years postoperatively and were salvaged. Multi-disciplinary decision-making utilizes the benefits of each specialty to optimize outcomes in de-escalation. Clinical trial information: NCT02072148 .