Perineural Invasion in Vulvar Squamous-Cell Carcinoma Is an Independent Risk Factor for Cancer-Specific Survival, but Not for Locoregional Recurrence: Results from a Single Tertiary Referral Center

SIMPLE SUMMARY: Vulvar squamous cell carcinoma is a rare tumor but represents a serious health issue, especially due to the increasing incidence over the past decades. Many efforts have been made to identify new prognostic and therapeutic factors and, in this context, growing evidence concerning a pivotal role of perineural invasion. With this study, we investigated the role of perineural invasion in a large cohort of FIGO stage Ib-IIIc vulvar squamous cell carcinomas and found that perineural invasion-positive tumors have more aggressive biological behaviors and showed reduced cancer-specific survival as compared to perineural invasion-negative tumors, while this feature does not appear to be related to a greater risk to develop loco-regional recurrence. Further evaluations are warranted to confirm the prognostic role of perineural invasion and its potential use to tailor adjuvant treatment. ABSTRACT: The aims of this study were to assess the prevalence of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) and its prognostic role in locoregional recurrence (LRR) and cancer-specific survival (CSS). We performed a retrospective analysis of 223 consecutive stage IB–IIIC surgically treated VSCCs at S. Anna Hospital, University of Turin, from 2000 to 2019. We identified 133/223 (59.6%) patients with PNI-positive VSCCs. PNI was associated with aggressive biological features (i.e., advanced FIGO stage, larger tumor diameter, greater depth of invasion, a higher number of metastatic lymph nodes, and lymphovascular invasion) and shorter 5-year CSS (78% vs. 90%, log-rank p = 0.02) compared with PNI-negative VSCCs. Multivariate analysis showed that PNI (HR 2.99 CI 95% 1.17–7.63; p = 0.02) and the presence of tumor cells on pathological surgical margins (HR 3.13 CI 95% 1.37–7.13; p = 0.007) are independent prognostic factors for CSS. PNI does not appear to be related to LRR, but is an independent prognostic factor for worse survival outcomes. Future studies are necessary to explore the possible value of PNI in tailoring the choice of adjuvant treatment.