Vulvar cancer : patterns of recurrence, quality of life and extended indications for the sentinel node technique

Abstract

Background: Vulvar cancer is a rare malignancy and few studies have addressed the course of disease and the impact of physical and psychological symptoms on healthrelated quality of life (HRQOL) over time. In addition, extending the indication for sentinel node biopsy in vulvar cancer requires further evaluation. The overall aim of this thesis was to investigate patterns of recurrence and the trajectory of symptoms and HRQOL in a nationwide population of women with vulvar cancer, and to examine the feasibility of sentinel node biopsy in larger and multifocal tumours.

Methods: Study I included all women diagnosed with primary vulvar squamous cell carcinoma (VSCC) from 2012-2015 whose health data were recorded in the Swedish Quality Registry for Gynaecologic Cancer (n=489). The cumulative incidences and survival rates for local, groin, and distant recurrences were calculated. In addition, the potential impact of not performing surgical groin staging on survival was assessed. In Studies II and III the relationship between physical and psychological symptoms and HRQOL in a nationwide longitudinal cohort of women with primary vulvar cancer diagnosed from 2019-2021 (n=153) were examined utilizing validated questionnaires (European Organisation for Research and Treatment of Cancer (EORTC)-QLQ C30, the EORTC-QLQ VU34, the Supportive Care Needs Survey, and the Hospital Anxiety and Depression Scale). Anxiety, depression, local vulvar and lymphoedema symptoms and their impact on HRQOL were investigated at the time of diagnosis, as well as 3 and 12 months after treatment. Study IV was a nationwide prospective, single-arm interventional pilot study. Women with VSCC and tumours ≥ 4 cm in diameter (Group 1), multifocal tumours (Group 2) or a first local recurrence (Groups 3 and 4) diagnosed between 2019-2022 (total n=64) underwent sentinel node biopsy in addition to standard inguinofemoral lymphadenectomy. Detection rates and negative predictive values were calculated.

Results: In Study I after a median follow-up of 52 months, the recurrence rate was 22.3% (vulva 61%, groin 30%, and distant 9%). Groin and distant recurrences occurred primarily within the first two years after treatment, while the incidence of local recurrences increased continuously during follow-up. The median two-year post-recurrence overall survival was 57.8% for vulvar, 17.2% for groin, and 0% for distant recurrences. Omission of surgical groin staging in 23.7% of the patients with presumed stage IB-II disease was associated with poorer survival. In Studies II and III 140 (92%) of the women completed at least one questionnaire and 105 (69%) completed all three. At the time of diagnosis, 41.8% of the women reported elevated anxiety, a proportion that declined to 29.5% 12 months after treatment. Insomnia, a high need for information and persistent vulvar symptoms were associated with enhanced anxiety. Vulvar symptoms were associated with impaired HRQOL and improved after treatment, whereas symptoms of leg lymphoedema became more common after treatment. Emotional, role, cognitive, and social functioning, as well as global and mental health became better following treatment. In Study IV, the detection rates in Groups 1 and 2 were 94.1–100% per patient and 84.1–85.3% per groin, respectively. There were no false-negative sentinel nodes, i.e., the negative predictive value was 100% (95% CI 91.2%-100% for Group 1 and 83.9%-100% for Group 2).

Conclusions: Local recurrences are common in patients with vulvar cancer, with a stable incidence throughout the period of surveillance. Lack of surgical groin staging is associated with poorer survival. Women with primary vulvar cancer report a high prevalence of vulvar symptoms, anxiety, and impaired HRQOL at the time of diagnosis. Alleviating vulvar symptoms, insomnia, and unmet needs for information might reduce anxiety. Extending the application of sentinel node biopsy to women with tumours ≥ 4 cm in diameter, as well as to those with multifocal tumours seems feasible.