Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)

Abstract

Background: For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery with or without SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial.

Methods: Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation. We evaluated recurrence site, therapy (selected by treating clinician), and survival after stage IV diagnosis.

Results: Of 291 patients with complete data for stage IV recurrence, 161 (55 %) underwent surgery with or without SMT. Median survival was 15.8 versus 6.9 months, and 4-year survival was 20.8 versus 7.0 % for patients receiving surgery with or without SMT versus SMT alone (p < 0.0001; hazard ratio 0.406). Surgery with or without SMT conferred a survival advantage for patients with M1a (median > 60 months vs. 12.4 months; 4-year survival 69.3 % vs. 0; p = 0.0106), M1b (median 17.9 vs. 9.1 months; 4-year survival 24.1 vs. 14.3 %; p = 0.1143), and M1c (median 15.0 vs. 6.3 months; 4-year survival 10.5 vs. 4.6 %; p = 0.0001) disease. Patients with multiple metastases treated surgically had a survival advantage, and number of operations did not reduce survival in the 67 patients (42 %) who had multiple surgeries for distant melanoma.

Conclusions: Our findings suggest that over half of stage IV patients are candidates for resection and exhibit improved survival over patients receiving SMT alone, regardless of site and number of metastases. We have begun a multicenter randomized phase III trial comparing surgery versus SMT as initial treatment for resectable distant melanoma.

Figure 1

Figure 1A. Overall survival for patients whose recurrent stage IV melanoma was treated with surgery ± SMT (n=161, median survival 15.8 months, 4-year survival 20.8%) versus systemic medical therapy alone (n=130, median survival 6.9 months, 4-year survival 7.0%). Figure 1B. Overall survival for patients by treatment received: surgery only (n=43, median survival 22.1 months, 4-year survival 45.7%), systemic medical therapy followed by surgery (n=33, median survival 17.1 months, 4-year survival 18.2%), surgery followed by systemic medical therapy (n=85, median survival 14.7 months, 4-year survival 12.3%), or systemic medical therapy alone (n=130, median survival 6.9 months, 4-year survival 7.0%). P value <0.0001.

Figure 1

Figure 1A. Overall survival for patients whose recurrent stage IV melanoma was treated with surgery ± SMT (n=161, median survival 15.8 months, 4-year survival 20.8%) versus systemic medical therapy alone (n=130, median survival 6.9 months, 4-year survival 7.0%). Figure 1B. Overall survival for patients by treatment received: surgery only (n=43, median survival 22.1 months, 4-year survival 45.7%), systemic medical therapy followed by surgery (n=33, median survival 17.1 months, 4-year survival 18.2%), surgery followed by systemic medical therapy (n=85, median survival 14.7 months, 4-year survival 12.3%), or systemic medical therapy alone (n=130, median survival 6.9 months, 4-year survival 7.0%). P value <0.0001.

Figure 2

Overall survival based on distant disease-free interval (DDFI). Overall survival is compared for patients with (A) long (≥12 months) and (B) short (<12 months) DDFI by use of surgery vs. systemic medical therapy alone for treatment of stage IV melanoma.

Figure 3

Figure 3A. Overall survival for patients with M1a recurrence treated with surgery ± SMT (n=26, median survival NA, 4-year survival 69.3%) vs. SMT alone (n=6, median survival 12.4 months, 4-year survival 0%). Figure 3B. Overall survival for patients with M1b recurrence treated with surgery ± SMT (n=27, median survival 17.9 months, 4-year survival 24.1%) vs. SMT alone (n=22, median survival 9.1 months, 4-year survival 14.3%). Figure 3C. Overall survival for patients with M1c recurrence treated with surgery ± SMT (n=108, median survival 15.0 months, 4-year survival 10.5%) vs. SMT alone (n=102, median survival 6.3 months, 4-year survival 4.6%).

Figure 3

Figure 3A. Overall survival for patients with M1a recurrence treated with surgery ± SMT (n=26, median survival NA, 4-year survival 69.3%) vs. SMT alone (n=6, median survival 12.4 months, 4-year survival 0%). Figure 3B. Overall survival for patients with M1b recurrence treated with surgery ± SMT (n=27, median survival 17.9 months, 4-year survival 24.1%) vs. SMT alone (n=22, median survival 9.1 months, 4-year survival 14.3%). Figure 3C. Overall survival for patients with M1c recurrence treated with surgery ± SMT (n=108, median survival 15.0 months, 4-year survival 10.5%) vs. SMT alone (n=102, median survival 6.3 months, 4-year survival 4.6%).

Figure 3

Figure 3A. Overall survival for patients with M1a recurrence treated with surgery ± SMT (n=26, median survival NA, 4-year survival 69.3%) vs. SMT alone (n=6, median survival 12.4 months, 4-year survival 0%). Figure 3B. Overall survival for patients with M1b recurrence treated with surgery ± SMT (n=27, median survival 17.9 months, 4-year survival 24.1%) vs. SMT alone (n=22, median survival 9.1 months, 4-year survival 14.3%). Figure 3C. Overall survival for patients with M1c recurrence treated with surgery ± SMT (n=108, median survival 15.0 months, 4-year survival 10.5%) vs. SMT alone (n=102, median survival 6.3 months, 4-year survival 4.6%).

Figure 4

Figure 4A: Overall survival for patients with stage IV recurrence of melanoma who had only one metastatic lesion treated by surgery (n=134) or SMT only (n=92). Figure 4B: Overall survival for patients with stage IV recurrence of melanoma who had two metastatic lesions treated by surgery (n=20) or SMT only (n=23). Figure 4C: Overall survival for patients with stage IV recurrence of melanoma who had three or greater metastatic lesions treated by surgery (n=7) or SMT only (n=15).

Figure 4

Figure 4A: Overall survival for patients with stage IV recurrence of melanoma who had only one metastatic lesion treated by surgery (n=134) or SMT only (n=92). Figure 4B: Overall survival for patients with stage IV recurrence of melanoma who had two metastatic lesions treated by surgery (n=20) or SMT only (n=23). Figure 4C: Overall survival for patients with stage IV recurrence of melanoma who had three or greater metastatic lesions treated by surgery (n=7) or SMT only (n=15).

Figure 4

Figure 4A: Overall survival for patients with stage IV recurrence of melanoma who had only one metastatic lesion treated by surgery (n=134) or SMT only (n=92). Figure 4B: Overall survival for patients with stage IV recurrence of melanoma who had two metastatic lesions treated by surgery (n=20) or SMT only (n=23). Figure 4C: Overall survival for patients with stage IV recurrence of melanoma who had three or greater metastatic lesions treated by surgery (n=7) or SMT only (n=15).