Gynecologic Melanoma: A 25-Year Institutional Experience

Abstract

<h3>Purpose/Objective(s)</h3> Melanoma of the gynecologic tract is a rare malignancy with poor outcomes. We sought to describe clinicopathological features, patterns of care, and outcomes in a large cohort of patients (pts) with this diagnosis treated at our institution. <h3>Materials/Methods</h3> Using an institutional pathology database we identified 141 pts with gynecologic melanoma treated 1995-2021. Clinicopathologic variables were described and time to outcome was calculated by the Kaplan-Meier method. <h3>Results</h3> Median age was 62 years (IQR 54-70). Primary tumors were located at the vulva (n=97, 69%), vagina (n=34, 24%) or cervix (n=10, 7%). Of the 123 pts with known primary tumor pathology, median tumor thickness was 5.0 mm (IQR 1.8-7.1 mm), 72% had ulceration (n=88), 21% had PNI (n=26), 28% had LVI (n=35), 6% had microsatellitosis (n=7) and 42% had a component of melanoma-in-situ (MIS, n=52) with 15% (n=21) having multifocal disease at presentation. Most pts had locally confined disease at diagnosis (n=110, 78%). Nine percent (n=13) had clinically involved nodes without distant metastasis (DM) and 13% had DM (n=18). At presentation 29 pts (21%) had unresectable disease, 2 of whom had surgery after response to neoadjuvant systemic therapy. Of the 112 pts with resectable disease, 77% (n=86) had nodal sampling with 40% of those (n=34) having pathologically positive nodes. Of the 105 pts with known margins: 47% R0 (n=49), 29% MIS+ (n=30), 21% R1 (n=22) and 4% R2 (n=4). Twenty-seven pts (23% resected) received neoadjuvant systemic therapy (11 pts at diagnosis and 16 pts at recurrence). Immune checkpoint inhibitors (ICI) were the most common class (67%, n=18). Ten pts (37%) had imaging or pathologic evidence of response to neoadjuvant therapy (6 ICI, 2 chemotherapy and 2 targeted therapy). Forty-three pts (37% resected) received adjuvant systemic therapy at the time of initial resection. Thirty-nine pts (28%) received pelvic RT during their treatment course. The primary tumor bed was the target for all except 2 pts who received RT to unilateral inguinal nodes and 1 pt who received RT to a pelvic sidewall mass. The timing of RT was: 1 neoadjuvant (3%), 15 adjuvant (38%), 14 to gross disease without DM (36%) and 9 to gross disease with DM (23%). The most common adjuvant regimens were 30 Gy in 5 fractions (n=6) or 48 Gy in 20 fractions (n=3). Of 141 pts, 79 (56%) were diagnosed after 2014, the era during which ICI were used. Median follow-up of those diagnosed pre-2014 was 98 months (mo, IQR 54-111 mo) and post-2014 was 39 mo (IQR 26-50 mo). Pre- vs. post-2014 3-year actuarial event rates were not significantly different with 59% vs. 49% local control (p=0.52); 56% vs. 60% nodal control (p=0.78); 45% vs. 34% DM-free survival (p=0.11); 25% vs. 20% disease-free survival; and 55% vs. 56% melanoma-specific survival (p=0.55). <h3>Conclusion</h3> Gynecologic tract melanoma outcomes continue to be poor with a significant need for improved treatment options, both in terms of pelvic and distant disease control.