ABSTRACT
BACKGROUND: Histopathologic regression of cutaneous melanoma is considered a favorable prognostic factor, but its significance in clinical practice remains controversial. OBJECTIVE: To investigate the prognostic importance of regression in patients with primary cutaneous melanoma undergoing sentinel lymph node (SLN) biopsy and to assess its significance in patients progressing to an unresectable stage requiring systemic therapy. METHODS: We retrospectively reviewed patients with newly diagnosed melanoma undergoing SLN biopsy between 2010 and 2015 and available information on histopathologic regression (n = 1179). Survival data and associations of clinical variables with SLN status were assessed. RESULTS: Patients with regressive melanoma showed favorable relapse-free (hazard ratio [HR], 0.52; P = .00013), distant metastasis-free (HR, 0.56; P = .0020), and melanoma-specific survival (HR, 0.35; P = .00053). Regression was associated with negative SLN (odds ratio, 0.48; P = .0077). In patients who progressed to an unresectable stage, regression was associated with favorable progression-free survival under immune checkpoint inhibition (HR, 0.43; P = .031) but not under targeted therapy (HR, 1.14; P = .73) or chemotherapy (HR, 3.65; P = .0095). LIMITATIONS: Retrospective, single-institutional design. CONCLUSIONS: Regression of cutaneous melanoma is associated with improved prognosis in patients eligible for SLN biopsy as well as in patients with unresectable disease receiving systemic therapy with immune checkpoint inhibitors.