Prolonged survival in patients with advanced melanoma treated with neoadjuvant chemotherapy followed by resection

Patients with metastatic melanoma (AJCC stage IV) generally have a very poor prognosis (median survival, 6-8 months). Combination chemotherapy is often the treatment of choice. Despite the higher response rates of a number of new combination regimens, the median duration of response ranges from 6 to 9 months, with no significant survival advantage. To evaluate whether surgical resection of residual metastases after chemotherapy can improve survival, we conducted a retrospective analysis of all patients enrolled on various chemotherapy protocols for metastatic melanoma at Yale between March 1987 and March 1993. We identified 16 patients who underwent surgical resection of residual disease after receiving one to four cycles of combination chemotherapy. Sites of metastases included regional and distant lymph nodes, skin, subcutaneous tissue, lung, and liver. No patients had brain or bone metastases at the initiation of therapy and performance status (PS) was 0.1. Follow-up for these 16 patients ranges from 14 to 62 months (median, 35 months) from the start of chemotherapy. All 16 patients had either complete responses (CR = 3) or partial responses (PR = 7), or stable disease (SD = 6) after chemotherapy. Eleven patients are currently alive; 10 remain free of disease. A comparison group (control) of 14 patients was identified from the same retrospective analysis using similar clinical characteristics such as sites of metastases, PS, and cycles of chemotherapy. No patients underwent surgical resection either because of patient refusal or concomitant medical problems. None had evidence of disease progression (CR = 3, PR = 2, SD = 9) at the completion of chemotherapy. However, duration of survival in this group from the start of chemotherapy ranged from 4 to 45 months (median, 11.5 months). Twelve patients have died and 2 are currently alive, 1 of which has recurrent disease. Based on the comparison of these two groups, this report suggests that patients treated with neoadjuvant chemotherapy may benefit from surgical resection of residual metastases, and this approach should be studied further.