Is Programmed Death Ligand 1(PD-L1) Expression in Vulvar Cancer Prognostic for Locoregional Control?

Abstract

Vulvar cancer is a rare female genital neoplasm in which surgery and radiotherapy play an integral role in the treatment paradigm; however, locoregional recurrence remains the predominant pattern of failure. Little is known about the impact of PD-L1 status in vulvar cancer and its value for clinical outcomes and response prediction to immunotherapy. We sought to explore clinical outcomes of patients with positive PD-L1 expression in vulvar cancer. Single-institution retrospective analysis of patients with surgically resectable invasive vulvar carcinoma from 2001-2021 was performed. Patients with locally advanced disease not amendable to upfront surgery or de novo metastatic disease were excluded. Immunohistochemical PD-L1 expression was assessed using the Combined Positive Score (CPS) with positive expression defined as ≥1, and Tumor Proportion Score (TPS) with positive expression defined as ≥1%. Survival and disease control outcomes were calculated using the Kaplan-Meier Method with log-rank t-test. Multivariable analysis was conducted using a parsimonious cox regression analysis using forward conditional selection. A total of 85 patients were identified with a median age of 69 years old (IQR: 59-78), 54% (n = 46) FIGO stage I-II, 97% (n = 82) squamous cell carcinoma histology, 41% (n = 35) p16 positive status, 74% (n = 63) without a history of lichen sclerosis, 40% (n = 34) without co-existing vulvar intraepithelial neoplasm (VIN), and 49% (n = 42) treated with surgery alone. There were 72% (n = 61) with positive PD-L1 TPS (≥1%), and 81% (n = 69) with positive PD-L1 CPS (≥1) expression. The median follow up was 49 months (IQR: 21-75 months). The 5-year OS was 79% (95% CI, 70%-89%), DFS 55% (95% CI, 43%-67%), local control (LC) 59% (95% CI, 47%-72%), regional control (RC) 86% (95% CI, 78%-94%), and distant metastasis (DM) 96% (95% CI, 92%-100%). PD-L1 expression was associated with lower LC and DFS by TPS ≥1%. The 5-year LC of 82% (95% CI, 65%-98%) for PD-L1 negative versus 50% (95% CI, 34%-65%) positive disease (p = 0.03). The 5-year DFS was 77% (95% CI, 59%-95%) for PD-L1 negative versus 46% (95% CI, 31%-61%) positive disease (p = 0.03). No significant DFS or LC difference was noted by CPS levels ≥1. No significant difference was observed for RC, DM, or OS. On multivariable analysis, PD-L1 TPS remained a significant predictor for LC (HR = 3.01, 95% CI, 1.07-8.95, p = 0.04). No significant difference in DFS was observed for PD-L1 TPS on multivariable analysis. PD-L1 expression is associated with higher rates of local recurrence and may represents a potentially important actionable target independent of p16 status to improve the predominant pattern of relapse in this uncommon malignancy.