136 - Examining the Impact of Combined P53 Status and PD-L1 Expression on Vulvar Cancer Outcomes

B. Elgohari¹, P. P. Patwardhan², R. Bhargava², P. Sukumvanich³, M. Courtney-Brooks³, M. Boisen³, J. L. Berger³, S. Taylor³, A. Olawaiye³, J. Lesnock³, R. P. Edwards³, T. R. Soong², and J. A. A. Vargo IV¹; ¹The University of Pittsburgh, Department of Radiation Oncology, Pittsburgh, PA, ²The University of Pittsburgh, Department of Pathology, Pittsburgh, PA, ³The University of Pittsburgh, Department of Gynecologic Oncology, Pittsburgh, PA

Purpose/Objective(s): Vulvar cancer (VC) has a heterogeneous microenvironment with complex cellular & molecular interactions, which poses a challenge to predict clinical outcomes. VC is commonly known to associated with 2 pathways: HPV dependent, and independent pathway. Little is known about the combined impact of p53 and PD-L1 expression on VC prognosis. We aimed to examine the combined impact of p53 status and PD-L1 expression on treatment outcomes for vulvar cancer. Materials/

Methods: A single institutional retrospective study of 90 VC patients treated from 2010 to 2021 was conducted. P53 status was evaluated for wild-type (p53wt) versus aberrant (p53a) by immunohistochemical (IHC) expression. Positive PD-L1 status (PD-L1+) was defined as a Combined Positive score of =1. VCs were classified into a 4-category scheme based on PD-L1 and p53 status (PD-L1/p53): PD-L1+/p53a; PD-L1+/p53wt; PD-L1-/p53a; PD-L1-/p53wt. Associations with outcomes including overall survival (OS), disease-free survival (DFS), local control (LC), & regional control (RC) were assessed via log-rank tests and multivariable Cox regression analyses.
Results: The median age was 72 years (IOR: 62–80). Most cases (n = 88) were squamous cell carcinoma, 48% of FIGO I-II, 35% were positive for p16, and close to half (44%) were PD-L1+/p53a (see table 1). Most (74%) received as initial treatment surgery± postoperative radio± chemotherapy (S+POT), versus 26% received upfront definitive chemoradiotherapy (DCRT). Median follow-up: 38 months (IQR: 17–66). The p53a VC showed a statistically significantly worse 5-yr OS (45%, 95 CI: 27–63) than the p53wt VCs (85%, 95 CI: 72–97) (p = 0.01) as with DFS, LC, and RC. We observed a significant difference in 5yr OS when patients were stratified by initial treatments received (table 1) and with 5-yr DFS, and RC as outcomes of measures. On multivariable analysis, PD-L1-/p53a status was associated with worse OS (HR: 3.6, 95 CI: 1.1–11.3) after controlling for p16 status, age, FIGO stage, and other clinicopathologic factors. Other PD-L1/p53 status groups were not found to be independent predictors of clinical outcomes.
Conclusion: These results suggest that PD-L1-/p53a VCs as a subtype are prognostic for worse OS. This classification suggests the complex interaction between p53 and PD-L1 and the potential prognostic significance for oncological outcomes. The PD-L1/p53 classification could help risk-stratify VCs in routine practice and potentially guide personalized therapy.

Abstract 136 – Table 1

	PD-L1+/p53a (44%)	PD-L1-/p53a (9%)	PD-L1+/p53wt (36%)	PD-L1-/p53wt (10%)	P</b>
5yr OS S+POT	69% (51-88%)	80% (45-100%)	94% (83-100%)	100% (NR)	0.05
5yr OS DCRT	13% (10-35%)	33% (20-87%)	50% (14-86%)	100% (NR)	0.04