Is Time to First Distant Recurrence of Advanced Melanoma Linked to Survival?

The time it took for metastatic melanoma to recur was not associated with progression-free survival or overall survival, according to a new study.

The study evaluated progression of metastatic disease in a group of 638 patients with unresectable stage III or IV melanoma taken from the French MelBase cohort. Included patients were treated with first-line immunotherapies (n = 274), targeted therapies (n = 180), or chemotherapy (n = 132).

“The association of the time interval between the primary excision and first distant relapse with survival has been debated in the literature, and contrasting opinions persist,” wrote Anaïs Vallet, MD, of Hopital St-Louis in Paris, and colleagues, in a study published in JAMA Dermatology.

However, in the last decade, the prognosis of patients diagnosed with advanced melanoma has been improved by new therapeutic regimens. In this study, Vallet and colleagues hypothesized that progression of metastatic disease would be associated with time from primary excision to first distant recurrence of melanoma.

The median time from primary excision to first distant recurrence was 25 months, with a median time to treatment initiation of 27 months.

No association was found between time to first distant recurrence and progression-free survival when it was evaluated as a continuous variable (hazard ratio [HR], 0.99; 95% CI, 0.99–1.01) or as a categorical variable (12 to 24 months: HR, 0.75; 95% CI, 0.56–1.03; > 24 months: HR, 0.62; 95% CI, 0.47–1.01).

Similarly, there was no association between time to first distant recurrence and overall survival when it was studied as a continuous variable (HR, 0.99; 95% CI, 0.98–1.02) or as a categorical variable (12 to 24 months: HR, 0.76; 95% CI, 0.54–1.07; > 24 months: HR, 0.61; 95% CI, 0.54–1.03).

Additionally, no interactions were found between time to first distant recurrence and Breslow thickness, or American Joint Committee on Cancer stage at diagnosis.

The researchers acknowledged that one limitation to the study was retrospective collection of dates of primary excision and relapses used in the MelBase cohort. In addition, they did not have an estimation of start of the disease from the patient’s point of view.

“Indeed, the data concerning the date when the patient first noticed the skin lesion are available for only 62.1% of the patients (396 of 638),” the researchers wrote. “This is the reason why we used the date of primary excision as the earlier event to evaluate time to first distant recurrence.”

In an editorial accompanying the study, Daniel G. Coit, MD, of Memorial Sloan Kettering Cancer Center, pointed out some weaknesses with the data and missed opportunities. However, he added that these data may reflect a change in contemporary treatment of patients with melanoma.

“As complete resection of metastatic disease has always been the most powerful prognostic variable among patients with melanoma undergoing metastasectomy with curative intent, now 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,” Coit said. “Response to systemic therapy, seen only anecdotally in the chemotherapy era, is now observed with increasing frequency, with clinical benefit defined as ranging from stabilization of previously progressive disease to increasingly frequent and durable complete remission of all known disease.”