Late recurrence in melanoma: clinical implications of lost dormancy

Abstract

Background: For patients with melanoma, if there has been no recurrence of disease 10 years after initial treatment, additional disease is believed to be very unlikely. However, such late recurrences are known to occur. The frequency of this phenomenon and its clinical significance are not well characterized due to the difficulty in obtaining relevant data. We examined a large, mature, institutional database to evaluate late recurrence.

Study design: The late recurrence cohort was defined as having a disease-free interval of 10 or more years after potentially curative treatment and was compared with an early recurrence cohort recurring within 3 years. Actuarial late recurrence frequency and factors associated with late recurrence were examined. Post-recurrence overall and melanoma-specific survival and prognostic variables were analyzed.

Results: Among all patients, 408 exhibited late recurrence (mean disease-free interval 15.7 years). For patients who received primary treatment at our institution with 10 or more years follow-up, 327 of 4,731 (6.9%) showed late recurrence. On an actuarial basis, late recurrence rates were 6.8% and 11.3% at 15 and 20 years, respectively, for those with no recurrence at 10 years. Late recurrence was associated with both tumor (thin, non-ulcerated, non-head/neck, node negative) and patient (younger age, less male predominant) characteristics. Multivariate analysis confirmed younger age, thinner and node negative tumors in the late recurrence group. Late recurrences were more likely to be distant, but were associated with better post-recurrence survival on univariate and multivariate analyses.

Conclusions: Late melanoma recurrence is not rare. It occurs more frequently in certain clinical groups and is associated with improved post-recurrence survival.

Figure 1

(A) Distribution of recurrence types in early recurrence (1, 2) and late recurrence (3, 4) for the overall cohort (1, 3) and for patients who had undergone negative surgical staging of regional lymph nodes at the time of presentation (2, 4). Light gray slice, regional metastasis; dark gray slice, distant metastasis. (B) Distribution of distant recurrence types, (1) early recurrence; (2) late recurrence (p=0.38). Light gray slice, M1a; medium gray slice, M1b; dark gray slice, M1c.

Figure 2

Melanoma-specific survival, comparison for late recurrence and early recurrence patients. (A) All patients combined; (B) by stage of recurrence.