Multidisciplinary management of very advanced stage III and IV melanoma: Proof-of-principle

Abstract

Abstract. Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3-307) months and 15 (1-156) months when calculated from the last intervention. Twenty-two males and 15 females, with a median age at diagnosis of 44 (20-71) years, with 13 trunk, 13 extremity, 3 head and neck and 8 unknown primary melanomas were included. There were 17 stage III and 20 stage IV patients with a median Breslow thickness of 3.7 (0.45-26) mm. Chemo/ chemobiotherapy achieved 7 clinical complete responses (cCRs), 28 partial responses (PRs) and 2 instances of stable disease. Six of the 7 cCRs were operated on, securing pathological complete response in 5 and PR in one. Four of these five and the PR patient still have no evidence of disease (NED). Twenty-one of 30 PR patients were rendered NED by surgery; 14 of these 21 patients succumbed to melanoma, and one is alive with stable disease. Overall, 11 of 37 patients have not succumbed to melanoma, with a median of 72 (14-156) months survival following the last intervention. Of the eight patients with unknown primary melanomas, five have not succumbed to melanoma, with a median of 89 (30-156) months survival following the last intervention. Patients with marginally resectable stage III and IV melanoma have a significant 30% chance, according to this series, for durable remission if treated by a multidisciplinary team in a melanoma center using induction chemobiotherapy and surgery. Results are more favorable for patients with an unknown primary lesion. In view of the currently approved new effective treatments for melanoma, this study may be considered a proof-of-principle investigation, enabling long-term remissions by combining induction therapy and surgery. IntroductionBased on the 2006 Surveillance Epidemiology and End Results (SEER) database, the incidence of melanoma is 19.6 per 100,000 population per year in the US, with mortality rates at 2.7 per 100,000 (1). Rates in Israel are not significantly different with 1,200 new cases being reported per year per 7,000,000 population. The favorable incidence to mortality ratio reflects the fact that most melanoma patients are diagnosed at an early, surgically curable stage. Approximately 8,400 patients per year in the US either presented with or developed incurable disease, and succumbed to melanoma (1).Although surgery provides the best opportunity for cure, it is frequently futile or impossible in patients with advanced stage III or IV metastatic disease. Thus, a multidisciplinary approach is an option that should be applied to this subgroup of patients, in an attempt at improving their outcome.In their 1998 phase I...

Malignant melanoma metastasis in the ileum: Two case reports

“…In 4%-12% of the intestinal metastasis of melanoma, it is impossible to determine the nature and localization of primary lesion 25 . Gutman et al 26 published a study of indications for surgical treatment of metastatic malignant melanoma of the gastrointestinal tract. Half of the patients in this study were considered for elective surgical treatment, and 22% of patients required urgent surgical treatment for intestinal obstruction or overt gastrointestinal bleeding.…”

“…Olila et al 27 have published the results of their research which show statistically significant prolongation of survival in surgically treated patients particularly those who had complete resection. Surgical treatment provides better survival compared to pharmacological or palliative ones [24][25][26][27][28][29][30][31] . Kadakia et al 32 published the results of studies in which 70% of anemia were present, as well as acute bleeding from the upper gastrointestinal tract, which was present in 50% of observed cases with metastasis of malignant melanoma in the gastrointestinal tract, while the others registered abdominal pain (60%), intestinal obstruction (47%), nausea and vomiting (41%), and gastrointestinal bleeding (30%).…”

Liver resection and ablation for metastatic melanoma: A single center experience

“…Several clinical trials analyzing novel therapies impact in stage IV melanoma patients including high rates of patients with visceral metastases have recently reported objective response rate up to 40% and median OS reaching 16.8 months namely with PD‐1 blockade . Preoperative induction immunochemotherapy followed by resection has been associated with prolonged survival and complete remission in advanced metastatic melanomas . Such an approach using induction therapies before metastasectomy will need further investigation.…”