Association of Histologic Regression With a Favorable Outcome in Patients With Stage 1 and Stage 2 Cutaneous Melanoma

Importance: Although regression is commonly observed in cutaneous melanoma, it is uncertain whether it is associated with patient prognosis. Objective: To determine whether histologically confirmed regression was associated with better or worse survival in patients with primary cutaneous melanoma. Design, Setting, and Participants: This cohort study analyzed data from 2 large cohorts of adults (one in the Netherlands and the other in Australia) with histologically proven, stage 1 and 2 primary, invasive cutaneous melanoma with known regression status treated between 2000 and 2014, with median follow-up times of 4.5 and 11.1 years for the Dutch and Australian cohorts, respectively. For the Dutch patients, population-based data from PALGA, the Dutch Pathology Registry, were used, and follow-up data were retrieved from the Netherlands Cancer Registry. For the Australian patients, data from the database of a large, specialized melanoma treatment center were used. Main Outcomes and Measures: Multivariable Cox proportional hazards analyses were performed per cohort to assess recurrence-free survival (RFS) and overall survival (OS), and subgroup analyses according to Breslow thickness category and melanoma subtype were performed. Results: A total of 17271 Dutch patients and 4980 Australian patients were included. In both cohorts, survival outcomes were better for patients with disease regression. For Dutch patients, the hazard ratio (HR) for those with disease regression was 0.55 (95% CI, 0.48-0.63; P <.001) for RFS and 0.87 (95% CI, 0.79-0.96; P =.004) for OS; for the Australian patients, the HR was 0.61 (95% CI, 0.52-0.72; P <.001) for RFS and 0.73 (95% CI, 0.64-0.84; P <.001) for OS. Subgroup analyses showed that the presence of regression improved RFS within thin and intermediate Breslow thickness melanomas in both cohorts. For patients with superficial spreading melanoma (SSM) subtype, regression improved RFS and OS in both cohorts. For Dutch patients with SSM, the HR for those with disease regression was 0.54 (95% CI, 0.46-0.63; P <.001) for RFS and 0.86 (95% CI, 0.76-0.96; P =.009) for OS; for the Australian patients with SSM, the HR was 0.67 (95% CI, 0.52-0.85; P =.001) for RFS and 0.72 (95% CI, 0.59-0.88; P =.001) for OS. Conclusions and Relevance: In 2 large patient cohorts from 2 different continents, regression was a favorable prognostic factor for patients with stage 1 and 2 melanomas, especially in those with thin and intermediate thickness tumors and those with SSM subtype.