Risk factors related to late metastases in 1,372 melanoma patients disease free more than 10 years

In many centers, Stage I-II melanoma patients are considered cured after 10 years of disease-free survival and follow-up visits are interrupted. However, melanoma may relapse also later. We retrospectively analyzed a cohort of 1,372 Stage I-II melanoma patients who were disease-free 10 years after diagnosis. The aim of this study was to characterize patients who experienced a late recurrence and to compare them to those who remained disease-free to identify possible predictive factors. Multivariate Cox proportional-hazards regression analyses were carried out to evaluate the influence of different factors on the risk of recurrence. Seventy-seven patients out of 1,372 (5.6%) relapsed, 52 in regional sites and 25 in distant ones. The majority of patients (31 out of 52) experienced late recurrence in regional lymph nodes. Brain and lung were the most common site of single distant recurrence (24% each). Patients with multiple distant metastases showed a brain and lung involvement in, respectively, 40 and 48% of cases. A Cox proportional-hazards regression model analysis showed the independent role of age under 40 years, Breslow thickness >2 mm, and Clark Level IV/V in increasing the risk of Late Recurrence. These patients should be followed-up for longer than 10 years. The pattern of recurrence suggests that melanoma cells can be dormant preferentially in lymph nodes, brain and lung. A particular attention should be reserved to these anatomic sites during the follow-up after 10 years of disease-free. What's new? After a period of apparent cure lasting 10 or more years, a small percentage of melanoma patients experience late recurrence, in which dormant tumor cells reemerge to cause disease. The factors that precipitate recurrence are unclear, however. In this study, risk of late recurrence in melanoma was found to be elevated among stage I-II patients who were under age 40 at diagnosis and had a Breslow thickness of more than 2 mm or a Clark level IV/V. The regional lymph nodes, brain, and lungs were primary sites of recurrence, suggesting that they are preferential sites of tumor cell dormancy.