Incidence, survival, and symptoms at recurrence among vulvar cancer patients treated with curative intent: a population-based cohort study.

Abstract

Vulvar cancer is a rare and mutilating disease with a high recurrence rate. Prior studies have reported relatively favorable survival rates after primary disease, while survival after recurrence is poor. Yet there is limited knowledge on recurrence and survival patterns following primary diagnosis, first, and second recurrence. Although many recurrences are local, their detection may be challenged by limitations in self-examination and inadequate knowledge of symptoms. Consequently, further knowledge of symptoms preceding a vulvar cancer recurrence may improve understanding of early manifestations to inform patient education and support early detection and treatment of recurrent disease. In this study, we aimed to describe recurrence incidences for first, second, and third recurrence, estimate overall survival following primary diagnosis, first, and second recurrence, and identify symptoms preceding first recurrence. We conducted a population-based nationwide cohort study in Denmark. All patients with primary vulvar squamous cell carcinoma who were prospectively registered in the Danish Gynecological Cancer Database during 2011-2022 and who underwent curatively intended treatment were included. Data were validated and enriched with data from hospital charts. The cumulative incidences of first, second, and third recurrence were estimated using the Aalen-Johansen estimator, accounting for death before recurrence as a competing event. Overall survival was estimated by the Kaplan-Meier method. Symptom analyses were descriptive and included symptom frequencies stratified by recurrence location and visual exploration of symptom co-occurrence using selected 2×2 tables and bar-chart summaries. We identified 800 patients with a median follow-up of 68.8 months (interquartile range (IQR) 39.7-104.9). The cumulative incidence of first recurrence was 19.2% (95% confidence interval (CI) 16.6-22.1) at 24 months and 35.0% (95% CI 31.3-38.8) at 120 months. The five-year overall survival following primary diagnosis was 73.3% (95% CI 69.9-76.3), decreasing to 38.2% (95% CI 31.5-44.9) following the first recurrence, though only to 49.8% (95% CI 40.1-58.7) following the first isolated local recurrence. More than half of the patients with a recurrence had an isolated local recurrence (n=149, 58.9%), one fourth had a distant recurrence (n=60, 23.7%), and only a few had either a locoregional (n=17, 6.7%) or an isolated regional recurrence (n=22, 8.7%). Median time from completion of primary treatment to local, locoregional, regional, or distant recurrence was 24.5 (IQR 10.5-43.7), 7.0 (IQR 3.9-23.7), 8.1 (IQR 4.9-13.3), and 9.0 (IQR 4.8-19.4) months, respectively. Nearly all patients with a local, locoregional, or regional recurrence experienced at least one out of several predefined symptoms preceding the first recurrence (n=213, 94.7%). The symptoms varied according to recurrence location. Itching often appeared alongside vulvar pain in local recurrences, while groin tumors frequently appeared with groin pain in regional recurrences. Vulvar cancer recurrences were common, with isolated local recurrences occurring at a relatively constant rate for up to nine years post-treatment. Overall survival after primary diagnosis was favorable but decreased markedly following first and second recurrence. Most recurrences were preceded by predefined symptoms, highlighting the importance of symptom awareness.