After a year, we're still having technical difficulties over here. All right. Hello, everyone. My name is Jillian O'Donnell. I'm a second year fellow in gynecologic oncology at the University of North Carolina at Chapel Hill. Thank you so much for the opportunity to speak to you all. Today, we'll be reviewing surgical management of vulvar cancer, including some practice-changing research that was presented in the last year. The objectives of this presentation are to review landmark trials, establishing the standard of care for surgical management of vulvar cancer, and to present the most recent literature and practice updates. To start with historical trials, GOG37 was a randomized controlled trial of 114 patients with a vulvar squamous cell carcinoma who had undergone radical vulvectomy, as well as bilateral inguinal lymphadenectomy. All patients had positive notes on final pathology. These patients were randomized to receive either bilateral inguinal and pelvic external beam radiation, or ipsilateral pelvic lymphadenectomy. This study demonstrated improved overall survival with the addition of radiation therapy as compared to lymphadenectomy alone. The two arms had similar rates of toxicity. Interestingly, 30% of patients with positive groin nodes also had positive pelvic nodes. They also found that patients who received radiation therapy with one positive node had better overall survival as compared to patients with two positive nodes, which was 80% versus 66% at two years. Lastly, they demonstrated a 5% recurrence rate in groins that had undergone both lymphadenectomy and radiation. GOG88 was a randomized controlled trial of 52 patients with a vulvar squamous cell carcinoma. They included patients with clinically negative groins, primary lesions with a depth of invasion greater than 5 millimeters, and who had undergone radical vulvectomy. They randomized patients to receive either bilateral inguinal lymphadenectomies with adjuvant ipsilateral radiation therapy to the groin and pelvis if positive, or radiation therapy alone to just the groin. The regimen used in this arm was 50 gray, localized to 3 centimeters below the skin surface. They demonstrated improved disease free survival in the lymphadenectomy arm, which was 92% versus 70% at two years. The lymphadenectomy arm saw a 48% rate of grade 3 wound breakdown, while the radiation arm saw a 37% rate of grade 3 desquamation. The study was criticized for the regimen used in the radiational bone arm. By localizing the radiation to 3 centimeters below the skin surface, it was hypothesized that deeper nodes were undertreated, especially in obese patients. And then the recurrence rate in this group was 19%. So in summary, GOG37 established external beam radiation to the dissected groin and pelvis, improves overall survival in node positive vulvar cancer as compared to surgery alone. GOG88 established the superiority of lymphadenectomy and external beam radiation, as opposed to radiation alone, and suggested that lymphadenectomy, in combination with radiation therapy, should be considered the standard of care for treatment of groin positive vulvar cancer. So GroinZV was a prospective observational study evaluating the role of sentinel lymph node biopsy in patients with clinical stage 1 vulvar cancer. It enrolled 403 women, which they then stratified into 623 separate groins, with a diagnosis of squamous cell carcinoma of the vulva, where the primary tumor measured less than 4 centimeters. All patients underwent sentinel lymph node biopsy using radiocolloid and blue dye, as well as pathologic ultrastaging. Patients with a tumor greater than 1 centimeter from the midline underwent ipsilateral procedures, while patients with a tumor less than 1 centimeter from the midline underwent bilateral procedures. Patients with negative sentinel nodes were dispositioned to surveillance. Patients with positive sentinel nodes were excluded from the study and underwent completion lymphadenectomy and standard of care management. It's important to note that standard pathologic assessment with H&E detected only 58% of metastases. Ultrastaging detected the other 42%. The rate of recurrence for all patients with a positive sentinel node was 3%, and this rate was reduced to 2.3% in patients with unifocal primary tumors. And predictably, patients who underwent sentinel lymph node biopsy had a much lower rate of morbidity than patients who underwent completion lymphadenectomy. So standard lymph node assessment involves sectioning the node once along the longitudinal axis and performing H&E staining to determine if it contains metastatic tumor cells. For sentinel lymph nodes, additional pathologic assessment is performed if the initial H&E is negative. This is called ultrastaging and involves additional sectioning and staining of the sentinel node with H&E and immunohistochemistry in order to identify low-volume metastatic disease. Lastly, GOG173 was a prospective observational study that was designed to validate the results of GROIN-C. 452 women with vulvar squamous cell carcinoma measuring between two and six centimeters limited to the vulva with a depth of invasion of at least one millimeter and clinically negative groin nodes underwent a sentinel node biopsy and completion lymphadenectomy. Patients with a tumor greater than two centimeters from the midline underwent ipsilateral procedures while patients with tumor less than two centimeters from the midline underwent bilateral procedures. They showed a 92.5% rate of detection of sentinel nodes. Their rate of positive nodes was 31.6%. The sensitivity of the procedure was 91.7% with a corresponding 8.3 false negative rate. The negative predictive value was calculated to be 96.3% with a false negative predictive value of 3.7%. This was reduced to 2% when considering only tumors smaller than four centimeters. In the study, 23% of lymph node metastases were detected only on ultrastaging. So in summary, these two trials helped to establish sentinel lymph node biopsy as an alternative standard of care approach to the treatment of certain women with vulvar squamous cell carcinoma. Those with clinically negative groins, unifocal tumors measuring less than four centimeters and no prior vulvar surgery affecting lymphatic drainage. Completion lymphadenectomy should be performed for failed mapping. Additionally, ultrastaging is critical in the detection of metastatic sentinel lymph nodes. The results of Groins V2 were presented at SGO in 2020 and introduced practice-changing data in this setting. This was an international prospective multicenter phase two treatment trial that occurred between December of 2005 and October of 2016. Stopping rules were implemented to monitor the number of groin recurrences. Their primary endpoint was groin recurrence and their secondary endpoint was groin recurrence. And their primary endpoint was morbidity. They included patients with unifocal invasive squamous cell carcinoma of the vulva measuring less than four centimeters with a depth of invasion greater than one millimeter. Negative preoperative imaging was required and could be CT, MRI, or ultrasound. They analyzed their survival data using the Kaplan-Meier method and groups were compared using the log-rank method. 1,552 women were eligible to participate. 1,218 of them had negative sentinel nodes while 324 had positive sentinel nodes. All patients with positive sentinel nodes underwent external beam radiation to the groin. The stopping rule was activated in June of 2010 after 54 months of accrual. Out of 82 patients with positive sentinels, nine had isolated groin recurrences. An interim analysis was performed which revealed that patients at risk for groin recurrence had a sentinel lymph node metastasis measuring more than two millimeters or had extra capsular extension. The protocol was amended such that patients with negative sentinels were dispositioned to surveillance. Patients with micrometastases or isolated tumor cells were dispositioned to radiation alone. And patients with macrometastases were dispositioned to completion lymphadenectomy plus external beam radiation if they had extra capsular extension or more than one metastasis. Here's a figure showing the breakdown of the number of patients with negative sentinels, micrometastases, and macrometastases post-stopping rule. This brings us to the abstract that was presented at SGO entitled Radiotherapy as an Alternative Treatment for Inguinal Femoral Lymphadenectomy in Vulvar Cancer Patients with a Metastatic Sentinel Node. They looked at the 160 patients who had micrometastases or ITCs. This group comprised 160 patients with immune follow-up of 23.9 months. 127 of them received radiation, 15 had complete lymphadenectomies, and 18 had no treatment. The patients who underwent radiation, 2% have recurred at two years compared to the group who received no treatment in which about 15% had recurred at two years. And there was no difference in the size of metastases between these two groups. There were 162 patients with macrometastases and immune follow-up time was 22.5 months. 52 of them had radiation therapy alone, 104 had completion lymphadenectomy plus or minus radiotherapy, and six got no treatment. The rate of recurrence in the radiation alone group was 25%, while in the lymphadenectomy group was 8.2%. Predictably, the toxicities were mildest in patients who received sentinel lymph no biopsies only, higher in patients who had sentinels and radiation, and the highest in patients that had sentinels with completion lymphadenectomy plus or minus radiation. And there were no grade four or five toxicities. So in conclusion, radiotherapy to the groin without complete lymphadenectomy in patients with a micromet in a sentinel node results in a very low recurrence rate. And they also demonstrated that radiation alone has a lower rate of long-term toxicity than lymphadenectomy. In addition, radiation alone is not a safe alternative to completion lymphadenectomy in patients with macrometastasis in a sentinel node. So thank you very much for your attention. We have a little bit of a whirlwind there, and if there's time, I'd be happy to take questions.

vulvar cancer

surgical management

lymphadenectomy

sentinel lymph node biopsy

radiotherapy