J. M. Dalman1, E. S. Blake1, G. Rocha1, A. P. Zarov1, C. A. Harter1, S. Fu3, C. V. Angeles2,3 1University Of Michigan Medical School, Ann Arbor, MI, USA 2University Of Michigan, Department Of Surgery, Ann Arbor, MI, USA 3University Of Michigan, Department Of Dermatology, Ann Arbor, MI, USA
Introduction: Metastatic melanoma with unknown primary (MUP) is a rare phenomenon that occurs in less than 0.3% of all melanoma cases. Studies suggest that this could be due to a robust host immune response leading to spontaneous complete primary melanoma involution, which may confer better prognosis. As immunotherapy becomes the mainstay of treatment for patients with advanced melanoma, it is critical to understand how best natural immune responses, such as MUP, intersect with immunotherapy to impact outcomes. We hypothesize that patients with MUP will have better overall survival than patients with melanoma of known primary following the administration of immunotherapy.
Methods: An institutional melanoma database with selected patients including date of melanoma diagnosis between 1998 and 2021 was queried (n=6448). Patients excluded were stage IA-IIIA, mucosal melanoma, and melanoma in situ. The final dataset included 59 patients with MUP (stage IIIB-D, 65%; IV, 36%) and 475 with known primary (Stage IIIB-D, 92%; IV, 8%) Patients were further stratified by having received immunotherapy and by stage: IIIB,C (n=156), with D excluded due to lack of stage IIID patients with MUP, or stage IV (n=43). Descriptive statistics and GraphPad Prism were utilized to generate demographic information and Kaplan-Meier curves comparing OS, respectively.
Results: Median follow-up was 3.7 years. Patients with MUP and those with known primary were similar in age (61 years), sex, and race. First site of metastasis was primarily nodal for MUP (60%) and lung for those with known primary (44%). The rate of complete lymph node dissection for patients with stage III melanoma was similar between MUP (63%) and known primary (54%). Overall median survival was 9.6 years for patients with MUP and 10.7 years for patients with known primary (p-value 0.23). When stratified by stage and those who received immunotherapy, there was no difference in OS in stage IIIB/C patients between MUP and those with known primary (p-value 0.28). However, there was a trend towards better 5-yr overall survival for Stage IV MUP versus known primary patients who received immunotherapy (60% vs 35%, respectively, p-value 0.057).
Conclusion: These results suggest no benefit in OS in patients with MUP at baseline. However, in those who received immunotherapy, there was a trend towards improved OS in stage IV MUP compared to known primary patients, but no difference between groups with stage III disease. This supports future studies to examine the tumor microenvironment in MUP and primary melanomas with regression in order to understand the antitumor immune responses contributing to differences in immunotherapy outcomes during late stage disease.