Results of a retrospective study of patients with stage IV melanoma showed the kinetics of the disease between initial surgery and development of distant metastatic disease were not associated with response to first-line systemic therapy. The findings from this study were published in JAMA Dermatology.1

Controversy exists regarding whether the time from excision of the primary melanoma lesion to first evidence of distant recurrence is predictive of the course of metastatic disease, such as progression-free survival (PFS) and overall survival (OS).

Clinicopathologic data were collected for patients with stage IV melanoma enrolled in the French multicenter MelBase database between March 1, 2013 and September 1, 2017. Inclusion criteria included initially resectable disease, treatment with first-line single-agent immunotherapy, targeted therapy, or chemotherapy, or participation in an open clinical trial upon development of metastatic disease. Additional requirements for study inclusion included the availability of dates of primary excision, first distant recurrence, systemic therapy initiation, disease progression, and death.

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Of the 638 patients included in the study cohort, first-line treatment for metastatic disease consisted of monotherapy with immunotherapy (274 patients), targeted therapy (180 patients), chemotherapy (52 patients), or enrollment in a clinical trial (132 patients).

The median time from excision of the primary lesion to first evidence of distant recurrence was 25 months. No association was observed between time to first distant recurrence (TFDR) and PFS on first-line systemic therapy for metastatic disease when TFDR was analyzed as a continuous variable (hazard ratio [HR], 0.99; 95% CI, 0.99-1.01) or a categorical variable (12-24 months: HR, 0.76; 95% CI, 0.54-1.07; > 24 months: HR, 0.61; 95% CI, 0.54-1.03). Similarly, no association was found between TFDR and OS using either analysis method.

 “Our findings confirm more recent data concerning the unpredictability of cancer relapse,” the study authors noted in conclusion.

In commenting on the results of this study as they pertain to disease prognosis, the author of an accompanying editorial noted that “it is quite likely that a patient’s best response to immune and/or targeted therapy will emerge as much more important than the time it took for stage IV melanoma to become apparent.”2


1. Vallet A, Oriano B, Mortier L, et al. Association of time from primary diagnosis to first distant relapse of metastatic melanoma with progression of disease and survival [published online May 1, 2019]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.0425

2. Coit DG. The changing kinetics of advanced melanoma [published online May 1, 2019]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.0200