History and Updates of the GROINSS-V Studies

Surgical management of vulvar cancer is associated with high morbidity rates. The main aim of the GROINSS-V studies is reducing treatment-related morbidity by finding safe alternative treatment options in early-stage vulvar cancer patients. This article reviews the history, results, and updates of the GROINSS-V studies. The first GROINSS-V study was a multicenter observational study (from 2000 to 2006), which investigated the safety and clinical applicability of the sentinel lymph node procedure in patients with early-stage vulvar cancer. GROINSS-V-I showed that omitting inguinofemoral lymphadenectomy was safe in early-stage vulvar cancer patients with a negative sentinel lymph node, with an impressive reduction in treatment-related morbidity. GROINSS-V-II, a prospective multicenter phase II single-arm treatment trial (from 2005 to 2016) investigated whether radiotherapy could be a safe alternative for inguinofemoral lymphadenectomy in patients with a metastatic sentinel lymph node. This study showed that radiotherapy in patients with sentinel lymph node micrometastases (≤2 mm) was safe in terms of groin recurrence rate and with less treatment-related morbidity. These results, published in August 2021, should be implemented in (inter)national treatment guidelines for vulvar cancer. GROINSS-V-III recently started including patients. This study investigates the effectiveness and safety of chemoradiation in patients with a macrometastasis (>2 mm) in the sentinel lymph node

New Therapies in Vulvar Cancer

Major advances have been made in vulvar cancer treatment during the last decades, exploring less morbid treatment options without compromising survival. The introduction of the sentinel lymph node procedure is one of the most important advances in surgical management of early-stage vulvar cancer patients, resulting in a significant decrease in treatment-related morbidity. Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V) II is currently investigating the safety of replacing inguinofemoral lymphadenectomy by radiotherapy in patients with a metastatic sentinel lymph node. Targeted therapy in vulvar cancer is still in its infancy; preliminary results from pilot studies are promising, however large studies are lacking. Since vulvar cancer originates by two different pathways, an human papillomavirus (HPV)-dependent and HPV-independent type, studies on targeted therapy should take this into account

Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe

Objective: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. Methods: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. Results: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%–4.5%]) had a contralateral groin recurrence. Conclusion: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases

Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe

Objective. Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN.Methods. We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up.Results. Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was di-agnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor &amp;gt;= 30 mm. Bilateral ra-diotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence.Conclusion. The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).On behalf of all GROINSS-V I and II participants: C.F. Levenback, R.H. Hermans, J. Bouda, A. Sharma, D. Luesley, P. Ellis, D.J. Cruickshank, T.J. Duncan, K. Kieser,C. Palle, N.M. Spirtos, D.M. O'Malley, M.M. Leitao, M. Geller, K. Dhar, V. Asher, D.H. Tobias, C. Borgfeldt, J.S. Lea,M. Lood, J. Bailey, B. Eyjolfsdottir, S. Attard-Montalto, K.S. Tewari, P. Persson, R. Manchanda, P. Jensen, L. Van Le</p