Risk Factors for Recurrence in Vulvar Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

INTRODUCTION

Vulvar cancer is a rare malignancy, accounting for 5%-8% of gynecological cancers, most commonly vulvar squamous cell carcinoma (VSCC). Achieving adequate tumor-free margins is crucial for local control. Although current guidelines recommend margins of at least 8 mm, the optimal cut-off remains uncertain, as published evidence is inconsistent. Other clinicopathological factors may also influence recurrence, but data are limited given the rarity of VSCC. This meta-analysis aimed to evaluate the effect of margin width and additional prognostic factors on recurrence risk.

METHODS

We conducted a PRISMA-compliant systematic review and meta-analysis, registered in PROSPERO (CRD420251135659). PubMed, Scopus, and Cochrane were searched through September 2025 for surgical VSCC studies reporting tumor-free margin width and local recurrence. Pooled risk ratio (RR) and hazard ratio (HR) were estimated using random-effects models, with subgroup analyses and risk of bias assessed using ROBINS-I.

RESULTS

Twenty-eight cohort studies were included. Margins < 8 mm were associated with increased local recurrence (LR) (RR 1.42; 24.8% vs. 15.6% for ≥ 8 mm). No significant difference was found between 3-8 mm and < 3 mm, though recurrence was higher with < 3 mm. Margin width was not associated with regional or distant metastasis. Among patients with < 8 mm margins, adjuvant treatment were radiotherapy (22.5%) and re-excision (12.5%). Predictors of LR included tumor size (HR 1.53), lateral site (HR 1.60), depth of invasion (HR 2.51), lymph node positivity (HR 2.52), and higher FIGO stage (HR 1.77).

CONCLUSION

Tumor-free margins ≥ 8 mm are associated with a lower risk of local recurrence in VSCC. However, recurrence remains multifactorial, influenced by tumor size, depth of invasion, nodal involvement, and stage. Therefore, optimal management should combine adequate surgical margins with individualized adjuvant therapy tailored to the patient's risk profile.

TRIAL REGISTRATION: PROSPERO (CRD420251135659).