Inguinofemoral radiotherapy for patients with vulvar cancer and micrometastases in the sentinel node is safe alternative for inguinofemoral lymphadenectomy according to the GROINSS-V-II study investigators. The radiotherapy side effects were acceptable with less frequent treatment-related morbidity compared with inguinofemoral lymphadenectomy. However, in patients with sentinel node macrometastases, radiotherapy with a total dose of 50 Gy showed more isolated groin recurrences than inguinofemoral lymphadenectomy. The findings of the GROINSS-V-II study are published by Dr. Maaike H.M. Oonk of the University Medical Centre Groningen, University of Groningen in Groningen, the Netherlands and colleagues on 25 August 2021 in the Journal of Clinical Oncology.
The authors explained in the study background that the treatment for early-stage vulvar cancer has undergone major advances in the past years with introduction of the sentinel node procedure representing one of the major advances in vulvar cancer treatment. The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-I showed that inguinofemoral lymphadenectomy could be safely omitted in patients with negative sentinel node, resulting in significant decrease of morbidity. Patients with metastases in sentinel node currently need to undergo lymphadenectomy and suffer from morbidity of this treatment.
The primary aim of the GROINSS-V-II study was to establish whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy in patients with vulvar cancer and metastatic sentinel node. The secondary aim was to establish the short- and long-term treatment-related morbidity for this management strategy. The study provided the opportunity to collect further data on the safety of omitting inguinofemoral lymphadenectomy in patients with a negative sentinel node. Stopping rules were defined for the occurrence of groin recurrences.
The GROINSS-V-II was a prospective multicentre phase II single-arm study that included patients with early-stage vulvar cancer (diameter <4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment of local excision with sentinel node biopsy. If the sentinel node was involved (metastasis of any size), inguinofemoral radiotherapy of 50 Gy was delivered. The study primary endpoint was isolated groin recurrence rate at 24 months.
From December 2005 to October 2016, the study investigators registered 1,535 eligible patients from whom 322 patients (21.0%) had metastasis in the sentinel node. In June 2010, with 91 included patients with positive sentinel node, the stopping rule was activated because the isolated groin recurrence rate in this group was above predefined threshold.
Among 10 patients with an isolated groin recurrence, 9 had sentinel node metastases >2 mm and/or extracapsular spread. The protocol was amended so that those with sentinel node macrometastases (>2 mm) underwent inguinofemoral lymphadenectomy as a standard of care, whereas patients with sentinel node micrometastases (≤2 mm) continued to receive inguinofemoral radiotherapy.
Among 160 patients with sentinel node micrometastases, 126 received inguinofemoral radiotherapy, with 1.6% of an ipsilateral isolated groin recurrence rate at 2 years. Among 162 patients with sentinel node macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent inguinofemoral lymphadenectomy (p = 0.011).
Treatment-related morbidity after radiotherapy was less frequent compared with inguinofemoral lymphadenectomy.
The authors concluded that in the GROINSS-V-II study, radiotherapy showed to be similarly safe as compared to GROINSS-V-I data in terms of groin recurrence rate for patients with sentinel node micrometastases. The morbidity of inguinofemoral radiotherapy was less compared with lymphadenectomy. However, for patients with sentinel node macrometastases, the recurrence rate was higher with radiotherapy. For them, standard therapy remains lymphadenectomy, and further research is needed. Radiotherapy dose escalation in combination with chemotherapy will be investigated for such patients in GROINSS-V-III.
The authors commented that inguinofemoral radiotherapy could spare patients with vulvar cancer and sentinel node micrometastases the morbidity of lymphadenectomy and advocated to implement this in (inter)national treatment guidelines for vulvar cancer.
The study was supported by the Dutch Cancer Society (KWF Kankerbestrijding), NRG Oncology.
Oonk MHM, Slomovitz B, Baldwin PJW, et al. Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II. JCO; Published online 25 August 2021. DOI: 10.1200/JCO.21.00006.