Sentinel lymph node procedure in patients with recurrent vulvar squamous cell carcinoma: a proposed protocol for a multicentre observational study

Abstract

Background: Standard groin treatment in recurrent vulvar cancer consists of uni- or bilateral inguinofemoral lymphadenectomy (IFL), whereas in the primary setting women with selected unifocal tumours will undergo a sentinel lymph node (SLN) procedure. The SLN procedure results in fewer short and long-term sequelae compared to IFL, but some concerns must first be considered. Lymph drainage of the vulvar region can be affected by a previous surgery, which might reduce the number of detectable SLN nodes (feasibility) but increase the chance of encountering aberrant lymph drainage patterns such as bilateral SLNs in lateral tumours or SLNs at unexpected locations. Therefore, the SLN procedure potentially carries a higher risk of groin recurrence if a tumour positive node is not retrieved, but may also improve outcomes for women with aberrant drainage patterns. Since the relative benefits and drawbacks of the SLN procedure are still unclear we will investigate the safety of the SLN procedure in women with a first recurrent vulvar cancer. In a simultaneously started registration study we prospectively gather information on women with a first recurrence of vulvar cancer ineligible for the SLN procedure.

Method: In this prospective multicentre observational study all women with a first recurrence of vulvar cancer will be asked to consent to the collection of information on their diagnostics, treatment and outcome, and to complete quality of life and lymph oedema questionnaires. Women with unifocal tumours smaller than 4 cm and unsuspicious groin nodes will be offered the SLN procedure, with follow-up every 3 months together with imaging at 6 and 12 months when the SLN is tumour negative. The primary outcome is groin recurrence within 2 years of initial surgery. A total of 150 women with negative SLNs will be required to demonstrate safety, a stopping rule will apply and an extensive statistical analysis has been designed.

Discussion: Should the SLN procedure prove feasible and safe in recurrent vulvar cancer, it will be available for implementation in clinics worldwide. The inclusion of women ineligible for the SLN procedure in the current prospective study will help to bridge knowledge gaps and define future research questions.

Trial registration: Medical Ethical Committee approval number NL70149.078.19 (trial protocol version 2.0, date March 2nd, 2020). Affiliation: Erasmus Medical Centre. Dutch trial register NL8467 . Date of registration 19.03.2020.

Keywords: Recurrence; Sentinel lymph node; Vulvar cancer.

Fig. 1

Flowchart of the study design. Legend: SLN: Sentinel Lymph node, V-SCC; vulvar squamous cell cancer. USS; ultrasound scan of the groins, IFL Inguinofemoral lymphadenectomy

Fig. 2

Estimated guess of sample size to include 150 cases with a tumour negative SLN. Legend: SLN: Sentinel Lymph node, V-SCC; vulvar squamous cell cancer. * see text for all in- and exclusion criteria, **inclusion and exclusion criteria applicable to local tumour, but strong suspicion or evidence of tumour positive lymph nodes (clinical, radiological or proven with fine needle aspiration or biopsy)

Fig. 3

Stopping rule of SLN procedure. Legend: The stopping rule is activated when the number of groin recurrences (Y as) related to the number of patients with a negative SLN exceeds the line. * see text for all in- and exclusion criteria, **inclusion and exclusion criteria applicable to local tumour, but strong suspicion or evidence of tumour positive lymph nodes (clinical, radiological or proven with fine needle aspiration or biopsy)