A Novel Insight of Pathological Parameters Involved in Recurrence and Survival of Patients with Vulvar Cancer: the Importance of Perineural Infiltration and Patterns of Invasion

Objectives: Because our knowledge related to prognostic factors for vulvar cancer is limited and inconsistent, our objective is to determine the clinicopathologic parameters and to identify their prognostic impact on recurrence and survival.Methods: Patients with squamous vulvar cancer treated at our institution between 2000 and 2012 (n = 175) were retrospectively analyzed and further evaluated regarding the prognostic significance of different clinicopathologic variables, including age, diameter and location of the lesion, clinical tumor characteristics, depth of invasion, grade, lymphovascular space involvement (LVSI), and presence of vulvar intraepithelial neoplasia. Furthermore, the significance of perineural invasion and the types of invasive pattern were also evaluated. Time to recurrence was recorded, and disease-free survival and overall survival calculated. Cox regression analysis was used to identify factors independently associated with recurrence and survival.Results: Multiple analysis of all tumor-related variables showed that the number of positive lymph nodes (LNs) was the only independently associated risk factor for recurrence. In addition, increased depth of invasion and tumor thickness were associated with greater risk for recurrence ([HR 1.20, 95% CI 1.16–1.25] and [HR 1.10, 95% CI 1.08–1.12], respectively). Cases with invasive or spray invasive pattern had greater risk for recurrence in a comparison of cases with confluent invasive pattern. The presence of LVSI and perineural invasion were also associated with 74% and 67% greater risk for recurrence, respectively (HR 1.74, 95% CI 1.02–2.96 and HR 1.67, 95% CI 1.00–2.79]. Also, multiple Cox regression analysis in a stepwise method showed that age at diagnosis, free surgical margins, and the total number of positive LNs were independently associated with survival.Conclusions: LN metastasis and status of surgical margins were confirmed to be independent predictors for poor prognosis. Furthermore, number of positive LNs, spray invasive pattern, and perineural invasion correlated with increased risk for recurrence. These findings should be considered when identifying high-risk patients for further adjuvant therapy to prevent recurrence. Objectives: Because our knowledge related to prognostic factors for vulvar cancer is limited and inconsistent, our objective is to determine the clinicopathologic parameters and to identify their prognostic impact on recurrence and survival. Methods: Patients with squamous vulvar cancer treated at our institution between 2000 and 2012 (n = 175) were retrospectively analyzed and further evaluated regarding the prognostic significance of different clinicopathologic variables, including age, diameter and location of the lesion, clinical tumor characteristics, depth of invasion, grade, lymphovascular space involvement (LVSI), and presence of vulvar intraepithelial neoplasia. Furthermore, the significance of perineural invasion and the types of invasive pattern were also evaluated. Time to recurrence was recorded, and disease-free survival and overall survival calculated. Cox regression analysis was used to identify factors independently associated with recurrence and survival. Results: Multiple analysis of all tumor-related variables showed that the number of positive lymph nodes (LNs) was the only independently associated risk factor for recurrence. In addition, increased depth of invasion and tumor thickness were associated with greater risk for recurrence ([HR 1.20, 95% CI 1.16–1.25] and [HR 1.10, 95% CI 1.08–1.12], respectively). Cases with invasive or spray invasive pattern had greater risk for recurrence in a comparison of cases with confluent invasive pattern. The presence of LVSI and perineural invasion were also associated with 74% and 67% greater risk for recurrence, respectively (HR 1.74, 95% CI 1.02–2.96 and HR 1.67, 95% CI 1.00–2.79]. Also, multiple Cox regression analysis in a stepwise method showed that age at diagnosis, free surgical margins, and the total number of positive LNs were independently associated with survival. Conclusions: LN metastasis and status of surgical margins were confirmed to be independent predictors for poor prognosis. Furthermore, number of positive LNs, spray invasive pattern, and perineural invasion correlated with increased risk for recurrence. These findings should be considered when identifying high-risk patients for further adjuvant therapy to prevent recurrence.