Competing risks survival of older patients with metastatic cutaneous melanoma: a SEER population-based study

Mortality from metastatic cutaneous melanoma is substantially heterogeneous as reflected in three distant metastatic (M1) subtypes with metastasis to skin, subcutaneous tissue, or distant lymph nodes (M1a), conferring nearly half the risk of death compared with distant visceral metastasis (M1c). It remains unknown whether older patients experience the survival benefit from the M1a subtype given a higher overall mortality risk. Surveillance, Epidemiology, and End Result data were retrieved from 1878 metastatic melanoma patients, from 2005 to 2009, with follow-up through 2011. Hazard ratios (HRs) for 2-year overall survival were estimated for M1 subtypes among older (≥65) and younger (<65) patients. Proportional subdistribution hazard ratios (SHRs) were calculated for melanoma-specific and competing risk mortality. For both older and younger patients, worse overall survival was observed for the M1c compared to the M1a subtype [HR: 2.65, 95% confidence interval (CI): 2.02-3.49; and, SHR: 3.36, 95% CI: 2.56-4.41; respectively]. For competing mortality, older compared to younger patients had increased risk in the M1a and M1b subtypes (SHR: 6.07, 95% CI: 1.94-19.0, and SHR: 2.34, 95% CI: 1.08-5.05, respectively). Conversely, when examining melanoma-specific mortality, older patients had decreased risk in M1a and M1b subtypes (SHR: 0.28, 95% CI: 0.14-0.53, and SHR: 0.60, 95% CI: 0.38-0.94, respectively) compared to those under 65 years. The persistent prognostic advantage of M1a among older patients should be considered when calculating the risk-benefit ratio for treatment. Prior reports of a protective effect of older age on melanoma-specific mortality, when based on traditional competing risks analyses, might be explained as an artifact of increased competing mortality risk.