Site and timing of first relapse in stage III melanoma patients: implications for follow-up guidelines

Abstract

Purpose: Stage III melanoma is associated with a high risk of relapse and mortality. Nevertheless, follow-up guidelines have largely been empirical rather than evidence-based.

Patients and methods: Clinical records of stage III patients with no evidence of disease seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1992 and 2004, who ultimately relapsed, were reviewed retrospectively to evaluate date of first relapse, time to first relapse, method of first relapse detection, and survival. We also determined overall 5-year relapse-free survival (RFS) of all stage III patients seen at MSKCC during this period.

Results: The overall 5-year RFS for stage IIIA, IIIB, and IIIIC patients was 63%, 32%, and 11%, respectively. Among relapsing patients, 340 had adequate follow-up to be evaluable for all parameters. Site of first relapse was local/in-transit (28%), regional nodal (21%), or systemic (51%). First relapses were detected by the patient or family, physician, or by screening radiologic tests in 47%, 21%, and 32% of patients, respectively. Multivariate analysis revealed that better overall survival was associated with younger age and first relapse being local/in-transit or nodal, asymptomatic, or resectable. For each substage, we estimated site-specific risk of first relapse.

Conclusion: Patients detected almost half of first relapses. Our data suggest that routine physical examinations beyond 3 years for stage IIIA, 2 years for stage IIIB, and 1 year for stage IIIC patients and radiologic imaging beyond 3 years for stages IIIA and IIIB and 2 years for stage IIIC patients would be expected to detect few first systemic relapses.

Fig 1.

(A) Relapse-free survival of all 340 patients with melanoma substages IIIA, IIIB, and IIIC who relapsed. Relapse-free survival was estimated separately for patients with substages IIIA (B), IIIB (C), and IIIC (D) by anatomic site of first relapse. (E) Site of first relapse and method of its detection. Local and in-transit recurrences are combined. LN, lymph node.

Fig 2.

Site of first systemic relapses in patients with initial diagnosis of melanoma substages IIIA (A), IIIB (B), and IIIC (C). Subcut, subcutaneous; LN, lymph node.

Fig A1.

(A) Dot plot of the average number of months between physician (MD) visits (months of progression-free survival [PFS]/number of medical oncology, surgical, or dermatologic visits in patients who had melanoma with resectable versus unresectable first relapses; P = .63, not significant). Data are calculated as total number of medical oncology, surgical, or dermatologic visits divided by total months of PFS. (B) Dot plot of the number of months from last MD visit until first relapse (P = .4, not significant). First recurrences before the next scheduled MD visit were detected by symptoms. Data were available for 72% of patients. Horizontal lines indicate median values.

Fig A2.

Time to first relapse among patients with melanoma substages IIIB and IIIC whose first relapse was in the brain.

Fig A3.

Kaplan-Meier estimates of overall survival for patients with melanoma substages IIIA, IIIB, and IIIC from time of first relapse. Tick marks represent censored patients.