Abstract
Recent landmark trials have suggested a survival benefit to definitive tumor directed therapies (DTDT) for selected patients with metastatic disease for various malignancies. We sought 1) to confirm the prognostic significance of metachronous oligometastatic burden for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and 2) to evaluate disease outcomes for oligometastatic HPV-associated OPSCC after upfront DTDT versus upfront systemic therapy.
This was a single institution retrospective observational cohort study of patients with HPV-associated OPSCC who developed metachronous metastases ≥3 months after primary treatment with trans-oral robotic surgery (TORS) from 2008-2017. At metastatic presentation, patients were classified as oligometastatic (≤5 metastases) or polymetastatic (> 5 metastases). Treatment was classified as DTDT (all metastases initially treated with surgery/radiotherapy) or as upfront systemic therapy. Overall survival (OS) was compared using log-rank tests at a significance of P < 0.05. Univariable and multivariable (MV) Cox proportional hazard models were used to assess the association of patient, disease, and treatment characteristics with survival. Variables with P < 0.15 on univariable analysis (initial metastatic treatment, metastatic site, and number of metastases) were included in the multivariable model.
Of 676 patients undergoing primary surgical management for HPV-associated OPSCC, 36 patients subsequently developed metachronous metastases. For those 36 patients, the median follow-up time after surgery was 27.5 months (range 4.5-127.0), and the median OS was 42.8 months. The median age at distant metastasis was 62 (range 32-86), and most patients were male (86.1%) and Caucasian (97.2%). Overall, 27 patients presented with oligometastasis and 9 with polymetastasis. Oligometastatic patients had improved median OS compared to polymetastatic patients (47.9 vs. 22.7 months, P = 0.020). For the 27 oligometastatic patients, 12 were initially treated with DTDT while 15 received systemic therapy. DTDT was associated with an improved median OS when compared to systemic therapy (median OS not reached for DTDT vs 40.7 months, P = 0.021), with 3 year OS of 90.0% and 55.0% respectively. DTDT was also associated with improved OS on MV Cox regression (hazard ratio = 0.06, 95% CI 0.004-0.73, P = 0.027) compared to systemic therapy when controlling for number of metastases and metastatic site.
Our study findings suggest that the extent of metastatic disease at metastatic presentation is related to prognosis, with oligometastasis associated with improved overall survival compared to polymetastasis. Among patients with oligometastatic disease, initial DTDT is associated with superior overall survival when compared to upfront systemic therapy.