Background: Early stage invasive squamous cell carcinoma of the vulva is treated by radical excision of the primary tumor combined with a sentinel node (SN) procedure for the groins. GROINSS-VI and GOG-173 demonstrated that if there is no metastasis to the SN, then standard of care is observation. GROINSS-VII/GOG-270 demonstrated that micrometastatic disease (<2mm) to the SN requires standard radiotherapy (50 Gy) without the need for an inguinofemoral lymphadenectomy (IFL). This study also found that patients with macrometastasis ( > 2mm) required IFL in order to have an acceptably low groin recurrence rate. However, IFL is associated with significant morbidity such as lymphedema, wound healing issues, and recurrent infections. It is hypothesized that for those with macrometastasis ( > 2 mm) in the SN, the efficacy of treatment can be increased by giving a higher dose of radiotherapy along with chemosensitization. Methods: This is an international multicenter single-arm phase II prospective clinical trial. The primary objective is to investigate the safety of replacing IFL by chemoradiation in early-stage vulvar cancer patients with a macrometastasis ( > 2mm) and/or extracapsular extension in the SN. The primary endpoint is the groin recurrence rate in the first two years after primary treatment. Secondary endpoints are short and long-term morbidity associated with the SN procedure and chemoradiation and quality of life as measured by EORTC-QLQc30. Patients with invasive ( > 1mm) squamous cell carcinoma of the vulva, stage T1, tumor size < 4 cm diameter and no suspicious lymph nodes by imaging of the groins will proceed with SN detection. Institutions enrolling patients must demonstrate prior surgical experience with SN detection with the submission of at least 10 successfully completed cases in vulvar cancer. Patients with SN metastases > 2mm and/or with extracapsular extension or those with > 1 SN with micrometastases will be eligible for this study. Treatment will consist of chemoradiation with a dose of 56 Gy to the groin combined with weekly cisplatin 40 mg/m2 IV on days 1, 8, 15, 21 and 29 of radiotherapy. One hundred and fifty-seven patients in Europe, United States and Canada will be enrolled. The study includes continuous monitoring of groin recurrences with stopping rules. Results of this trial may be practice changing and eliminate the need for IFL in all women with clinically early stage vulvar cancer. The study is currently open for enrollment. Clinical trial information: NCT05076942.