Expanding the Role for Metastasectomy in Advanced-Stage Melanoma

Historically, stage 4 melanoma was considered incurable. In these cases, metastasectomy was performed for only as a palliative measure. But with recent advancements in systemic therapy, metastasectomy has emerged as an effective tool for extending the period of disease control and enhancing overall treatment response. Dana-Farber Brigham Cancer Center is at the forefront of this transformation.

Charles H. Yoon, MD, PhD, FACS, is the director of surgery for cutaneous oncology and melanoma at Dana-Farber Brigham Cancer Center, the cancer center of Dana-Farber Cancer Institute and Brigham and Women’s Hospital. He notes that prior to 2016, stage 4 melanoma had a five-year survival rate of less than 5% and average survival of 13 months. The advent of immunotherapy and targeted therapy has since improved the prognosis, thus expanding the role for surgery.

According to Dr. Yoon, most patients with stage 4 melanoma who receive systemic therapy will have a partial response — the therapy will treat some but not all sites of metastatic disease.

“In that setting, you can carefully select patients who seem to be responding fairly well but have a few sites that remain persistent or enlarging but are surgically resectable,” he says. “By operating and removing the therapy-resistant sites in these patients, we have been able to extend the period of overall response to the systemic therapy. In essence, surgery has become an important adjunct to therapy, and we’re beginning to see more success with it.”

A Regional Leader in Metastasectomy for Melanoma

Dr. Yoon says that Dana-Farber Brigham Cancer Center annually sees over 100 patients with melanoma who are candidates for metastasectomy — one of the largest volumes in the Northeast. Given the center’s extensive experience with these patients, Dr. Yoon and Elizabeth J. Lilley, MD, MPH, then a surgical resident at the Brigham, decided to conduct a retrospective chart review study examining the efficacy of metastasectomy for melanoma.

Using a tissue bank database, Drs. Yoon and Lilley identified patients with stage 3 or 4 melanoma who received preoperative systemic treatment along with metastasectomy between 2010 and 2019. They categorized surgical intent as curative (resection of all metastatic disease), resection of isolated progression or palliative (for symptom relief).

Because immunotherapy and targeted therapy emerged in 2016 — and have been used regularly only since 2018 — the number of patients in the defined population was relatively small: Drs. Yoon and Lilley identified a total of 87 patients who underwent 127 procedures after immunotherapy (95%), targeted therapy (17%) or chemotherapy (22%).

The pair shared study details in a poster presentation at the Society for Surgical Oncology’s 2020 International Conference on Surgical Cancer Care. Among the key findings, overall survival after metastasectomy was 67% at one year and 38% at five years.

“Our review showed that combining surgery in advanced metastatic disease with systemic therapy seems to work fairly well in a population that previously had no options,” Dr. Yoon says. “The dataset is very small, and long-term studies and data on long-term outcomes are not yet available. But given the rapid advances for treatment of metastatic melanoma, there is great optimism for this approach.”

Buying More Time for Patients With Advanced-Stage Melanoma

Dr. Yoon and his colleagues at Dana-Farber Brigham Cancer Center continue to explore new ways to optimize the benefits of metastasectomy for melanoma. One area of focus is conducting selective surgery for generation of tumor vaccine or immune cells.

“Each tumor has its own population of tumor-infiltrating lymphocytes,” he explains. “We’re about to start the process of removing the tumors to study what’s working and not working. We also want to figure out how to manipulate those tumor-infiltrating lymphocytes to make them more effective when we reintroduce them back into the patient at some later time.”

For the time being, Dr. Yoon wants to get the message out that metastasectomy should be a consideration for many patients with advanced-stage melanoma.

“Surgery is clearly becoming more of an option for patients who in the past were deemed inoperable or for whom surgery did not seem to be a good idea prior to the advent of immunotherapy,” he says. “Through a combinatorial approach — using system therapy with surgery — we’re able to buy more time for these patients.”