Association of Time From Primary Diagnosis to First Distant Relapse of Metastatic Melanoma With Progression of Disease and Survival

Abstract

The prognosis of advanced melanoma has been greatly improved by new therapeutic agents and clinicians rely on dynamic signals to drive their therapeutic choices. Although the kinetics of metastatic disease seem to be correlated with survival, progression of the localized disease is not predictable. OBJECTIVE To assess whether progression of metastatic disease is associated with the time to the first distant recurrence of melanoma. DESIGN, SETTING, AND PARTICIPANTS This study was conducted from March 1, 2013, to September 1, 2017, among 638 adults with unresectable stage III or IV melanoma within the French multicentric prospective cohort MelBase. Patients treated with first-line immunotherapies, targeted therapies, or chemotherapy were included. Patients with unknown primary or de novo metastatic melanoma were not included. Data were analyzed from March 1, 2013, to December 1, 2017. MAIN OUTCOMES AND MEASURES The date of primary excision and time to first distant recurrence, progression-free survival, and overall survival were collected. Cox proportional hazards regression models were planned to assess the association between time to first distant recurrence and progression-free survival or overall survival, which was evaluated in terms of hazard ratio (HR). Time to recurrence was analyzed both as a continuous and categorical variable (<12 months, 12-24 months, and >24 months). RESULTS A total of 638 patients (272 women and 366 men; median age, 64 years [interquartile range, 52-73 years]) were included in the study. The median time from primary excision to first distant recurrence was 25 months (interquartile range, 12-55 months). There was no evidence of association of the time to recurrence with progression-free survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.99-1.01) or after categorization (12-24 months: HR, 0.75; 95% CI, 0.56-1.02; >24 months: HR, 0.62; 95% CI; 0.47-1.01). There was no evidence of association of the time to recurrence with overall survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.98-1.02) or after categorization (12-24 months: HR, 0.76; 95% CI, 0.54-1.07; >24 months: HR, 0.61; 95% CI, 0.54-1.03). Those results remained nonsignificant after stratification by treatment. CONCLUSIONS AND RELEVANCE In the MelBase cohort, time to recurrence of metastatic melanoma appears not to be associated with progression-free survival or overall survival.

The Changing Kinetics of Advanced Melanoma

“…Interestingly however, in the recent study by Faries et al 4 of the end results of the MMAIT randomized trial of metastatectomy with or without immune therapy for stage IV melanoma, with fairly broad inclusion criteria (resection of up to 5 metastatic sites), not only did the authors report a 5-year OS rate of around 40% after resection, in multivariable analysis, the time from primary diagnosis to randomization was not prognostic. This would seem to be consistent with the observations of Vallet et al 3 There is another potential explanation for the observations of Vallet et al 3 in this very contemporary cohort of patients with stage IV disease, one that most melanoma oncologists would prefer to embrace. In sharp contrast to bygone times, we now have therapy that can actually alter the kinetics of metastatic melanoma.…”

“…The second study, from Vallet and colleagues in Paris, 3 focused on the question of whether, in a cohort of patients with established distant recurrence after treatment of a known antecedent primary melanoma, the time from initial primary excision to the first distant recurrence was associated with progression-free (PFS) and overall (OS) survival (although not explicitly stated, these are assumed to be postrecurrence PFS and OS). The investigators queried MelBase, a multicenter collaborative French database of patients with unresectable stage III and stage IV melanoma.…”

Genetic Biomarkers in Melanoma of the Ocular Region: What the Medical Oncologist Should Know

“…Approximately 2% of patients with melanoma present with regional or distant metastasis as the first manifestation of the disease without a known primary melanoma [ 10 ]. These patients represent about 10–15% of all patients with hematogenously spread melanoma at any timepoint during their disease course [ 94 , 95 ]. Immunohistochemical markers used for diagnostic purposes of melanoma, e.g., HMB45 (gp100), tyrosinase, and Melan-A, are also often expressed in OcM and, thus, not able to distinguish between the different melanoma subtypes.…”

Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma

“… 16 , 18 , 19 Median time to recurrence and distant metastasis have been reported at 1.9 years and 2.1 years, respectively, indicating that the median follow-up time of 3.2 years in this study is sufficient to detect the majority of expected events. 28 , 29 Class 2 patients have a 3-year survival rate of 81%, which is lower than 5-year melanoma-specific survival for stage IIB-IIC patients (87% and 82%, respectively) for which AJCC 8th ed recommends increased imaging surveillance. These data suggest that class 2 patients may benefit from increased surveillance management for early detection of recurrence and metastasis.…”