Mohs surgery for female genital Paget's disease: a prospective observational trial.

BACKGROUND: Extramammary Paget's disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy. OBJECTIVE: This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget's disease. STUDY DESIGN: We conducted a prospective observational trial of patients with vulvar or perianal Paget's disease treated with surgical excision guided by Mohs micrographic surgery between 2018 and 2022. The multidisciplinary protocol consisted of office-based scouting biopsies and modified Mohs surgery followed by surgical excision with wound closure under general anesthesia. Modified Mohs surgery cleared peripheral disease margins using a moat technique with cytokeratin 7 staining. Medial disease margins (the clitoris, urethra, vagina, and anus) were assessed using a hybrid of Mohs surgery and intraoperative frozen sections. Surgical and oncologic outcomes were compared with the outcomes of a retrospective cohort of patients who underwent traditional surgical excision. The primary outcome was 3-year recurrence-free survival. RESULTS: Three-year recurrence-free survival was 93.3% for Mohs-guided excision (n=24; 95% confidence interval, 81.5%-100.0%) compared to 65.9% for traditional excision (n=63; 95% confidence interval, 54.2%-80.0%) (P=.04). The maximum diameter of the excisional specimen was similar between groups (median, 11.3 vs 9.5 cm; P=.17), but complex reconstructive procedures were more common with the Mohs-guided approach (66.7% vs 30.2%; P<.01). Peripheral margin clearance was universally achieved with modified Mohs surgery, but positive medial margins were noted in 9 patients. Reasons included intentional organ sparing and poor performance of intraoperative hematoxylin and eosin frozen sections without cytokeratin 7. Grade 3 or higher postoperative complications were rare (0.0% for Mohs-guided excision vs 2.4% for traditional excision; P=.99). CONCLUSION: Margin control with modified Mohs surgery significantly improved short-term recurrence-free survival after surgical excision for female genital Paget's disease. Use on medial anatomic structures (the clitoris, urethra, vagina, and anus) is challenging, and further optimization is needed for margin control in these areas. Mohs-guided surgical excision requires specialized, collaborative care and may be best accomplished at designated referral centers.

Invasive vulvar extramammary Paget's disease in the United States.

OBJECTIVE: To assess the incidence, treatment, and outcomes in patients with invasive vulvar extramammary Paget's disease (EMPD) in a national cohort of patients. METHODS: Patients from the Surveillance, Epidemiology and End Results (SEER) database with diagnoses of vulvar EMPD from 1992 to 2016 were included. Demographic, treatment, and outcome data were analyzed. RESULTS: A total of 1268 cases of invasive EMPD were identified. Of those, 69.6% had localized disease, 12.0% regional disease, 1.3% distant disease, and 17.1% were unstaged. The annual incidence of invasive vulvar EMPD was 0.36 per 100,000 person years: rates have increased >2-fold since 1992 (1992: 0.19 per 100,000 person years to 0.50 per 100,000 person years in 2016). Most patients underwent primary surgery (n = 1034; 81.5%). Five-year cancer specific survival (CSS) was 95.5% and was associated with stage. Compared to patients with localized disease, patients with distant metastases had dramatically worse CSS (HR: 85.8 (31.8-248) p < 0.0001). Synchronous cancers (diagnosed within one calendar year of EMPD diagnosis year) were observed in 35 cases (2.8%), and 195 patients (15.4%) developed a secondary malignancy (diagnosed >one year from year of EMPD diagnosis year). The most common synchronous breast, gastrointestinal tract, melanoma and the most common secondary cancers were breast, gastrointestinal tract and genitourinary tract. CONCLUSIONS: The incidence of invasive vulvar EMPD has increased over time. CSS is excellent for localized disease, but those with metastatic disease are in need of novel therapies. Approximately 15% will develop a secondary malignancy, indicating that patients with invasive vulvar EMPD should undergo site specific preventative health screens during recurrence surveillance.

Comparing risk stratification criteria for predicting lymphatic dissemination in endometrial cancer.

OBJECTIVE: To compare two published risk stratification models (Milwaukee Model vs. Mayo Criteria) to predict lymphatic dissemination (LD) in endometrioid endometrial cancer (EC). METHODS: Patients with stage I-III EC undergoing surgery from 1/1/2004-9/30/2013 were retrospectively reviewed and classified as low-risk vs at-risk for LD using two independent risk models. LD was defined as positive nodes at surgery or lymph node recurrence within 2 years of surgery after negative lymph node dissection (LND) or when LND was not performed. False positive (FP) and false negative (FN) rates for each risk model were calculated. RESULTS: Among 1103 patients, 81 (7.3%) had LD (72 positive LN and 9 LN recurrences), and most (90.2%) had stage I EC. The Milwaukee Model yielded a low at-risk rate for LD (38.1%) but a high FN rate (13.6%, 95% CI 7.0-23.0). The traditional Mayo Criteria using a cut-off of 2 cm for tumor diameter (TD) had a higher at-risk rate for LD (69.5%) but a FN rate of 0% (95% CI, 0-4.5). Modifying the Mayo Criteria using a TD cutoff of ≤3 cm identified fewer women at-risk (56.8% vs. 69.5%) and had a lower FP rate (53.6% vs. 67.1%), but had a higher FN rate (3.7%, 95% CI, 0.8-10.4). CONCLUSIONS: The Milwaukee Model had the lowest at-risk rate of LD but an unacceptable FN rate. Modifying the Mayo Criteria by increasing the TD cutoff from the traditional ≤2 cm to ≤3 cm would spare an estimated 13.5% of patients LND, but the accompanying FN rate is unacceptably high. The traditional Mayo Criteria for low-risk EC remains the most sensitive in determining which patients LND can be omitted.