Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases

The clinical treatment of patients with stage IV melanoma according to criteria of the American Joint Committee on Cancer (AJCC) is controversial because the 5-year survival rate is approximately 5%. Specific clinicopathologic factors are predictive of survival following curative surgery. Cohort analysis of 1574 successive patients undergoing surgical resection of metastatic melanoma for a 29-year period. Patients received follow-up on a routine basis with serial examinations and radiographic studies. The median follow-up time was 19 months (range, 1-382 months). Tertiary cancer center. Surgical resection was performed in 1574 patients. The decision to perform surgery was individualized for each patient. The technique of surgical resection was based on the site of metastasis. Main Outcome Measure Computer-assisted database with statistical analyses using log-rank tests and Cox regression models. Of the 4426 patients with AJCC stage IV melanoma, 1574 (35%) underwent surgical resection; 970 (62%) were men, with a median age of 50 years. Of the primary melanomas, 46% arose on the trunk, and 56% were Clark level IV or V with a median thickness of 2.2 mm. We found 697 patients (44%) to have AJCC stage III melanoma (lymph node) prior to the development of stage IV metastases. The most common site for resection was the lung (42%), followed by the skin or lymph node (19%) and the alimentary tract (16%). Of our patients, 877 (56%) had melanoma at a single site. The 5-year survival rate was significantly (P 36 months) disease-free interval from AJCC stage I or II to stage IV (P =.005) as predictive of survival. Our results demonstrate the benefit of surgical resection for advanced-stage melanoma. Patients with limited sites and numbers of metastases should be considered for curative resection regardless of the location of the disease.

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. 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. 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 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. 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.

On the basis of retrospective experience at individual centers, it appears that patients with stage IV melanoma who undergo complete resection have a favorable outcome compared with patients with disseminated stage IV disease. The Southwest Oncology Group (SWOG) performed a prospective trial in patients with metastatic melanoma who were enrolled before complete resection of their metastatic disease and provided prospective outcomes in the cooperative group setting. Based on their physical examination and radiologic imaging studies, patients with a stage IV melanoma judged amenable to complete resection underwent surgery within 28 days of enrollment. All eligible patients were followed with scans (computed tomography or positron emission tomography) every 6 months until relapse and death. Seventy-seven patients were enrolled from 18 different centers. Of those, 5 patients were ineligible; 2 had stage III disease alone; and 3 had no melanoma in their surgical specimen. In addition, 8 eligible patients had incompletely resected tumor. Therefore, the primary analysis included 64 completely resected patients. Twenty patients (31%) had visceral disease. With a median follow-up of 5 years, the median relapse-free survival was 5 months (95% CI, 3-7 months) whereas median overall survival was 21 months (95% CI, 16-34 months). Overall survivals at 3 and 4 years were 36% and 31%, respectively. In a prospective multicenter setting, appropriately selected patients with stage IV melanoma achieved prolonged overall survival after complete surgical resection. Although median relapse-free survival was only 5 months, patients could still frequently undergo subsequent surgery for isolated recurrences. This patient population is appropriate for aggressive surgical therapy and for trials evaluating adjuvant therapy. Copyright © 2011 American Cancer Society.