There have been significant strides in the systemic treatment of metastatic melanoma, but these advances have not meant the elimination of surgery as part of the management of metastatic melanoma. Learn more
Surgery is not a treatment modality that is outdated in the management of advanced melanoma, despite the existence of very effective novel treatments, according to Vernon K. Sondak, M.D., chair, Department of Cutaneous Oncology, Moffitt Cancer Center, in Tampa, Fla.
Speaking about the role of surgery in the era of immunotherapy at the 10th annual Canadian melanoma conference, Dr. Sondak noted that surgery remains a highly effective therapy for metastatic melanoma and it is often an element in the overall treatment for patients with advanced melanoma.
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"Surgery is not obsolete," he says. "We have to figure out how to use surgery as a component in this new and rapidly evolving world (of metastatic melanoma management)."
Unfortunately, even with more options for treatment, many patients will not survive metastatic melanoma, Dr. Sondak stresses.
"There has been a revolution in the management of (metastatic) melanoma," he says. "The new drugs, however, are not curing everyone who gets treated. Despite all the advances (in systemic treatments), the majority of patients will end up dying of their metastatic melanoma. A cure in a majority of patients is still elusive."
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Surgery can be highly effective as a sole modality, Dr. Sondak says, and he points to five-year-old data that concluded that 89% of patients with metastatic melanoma achieve "complete remission" (i.e., are rendered immediately disease-free) with surgery. The study looked at 77 patients at multiple sites who had Stage IV melanoma and were considered potential candidates for surgery to remove all known metastatic disease.1
"One thing that surgery does that no other treatment offers is complete remission for about 90% of patients," Dr. Sondak says.
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Dr. Sondak says the approach to treatment in the metastatic setting of melanoma is in constant change.
"Every week, we spend time at our tumor board discussing which patients should or should not undergo surgery," he says. "Years ago, we would have just operated on these patients and not given these cases a second thought. The data are coming fast, and clinical practice is changing. Our criteria (for surgery) are evolving almost on a weekly basis."
To date, there are no definitive predictors to know which patients will do well on a systemic agent like ipilimumab. Given that unpredictability, a consensus does not exist about the place of surgery in treatment, he says.
Dr. Sondak emphasizes that numerous health professionals including surgeons, medical oncologists, surgical oncologists, and radiation oncologists should be involved in the treatment decisions of patients with metastatic melanoma.
In the past, the standard approach to treating potentially resectable Stage IIIC-IV melanoma was to resect all known disease and consider adjuvant therapy. By contrast, in 2016, systemic therapies such as BRAF and MEK inhibitors are increasingly initiated first if patients have borderline resectable or even resectable Stage IIIC/IV BRAF V600 mutant melanoma, with surgery reserved for managing residual disease.
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"After BRAF inhibitor therapy and an operation, we would then wait and see what happens with that patient," he explains.
Depending on the genetic profile of the patients, they may or may not be candidates for BRAF inhibitors, Dr. Sondak notes. "Only about half of the patients carry BRAF mutations," he says.
For many patients with unresectable metastatic melanoma, immune checkpoint inhibitors, specifically anti-PD1 antibody therapies, are being increasingly initiated, particularly if patients are not regarded as good candidates for surgery.
The use of imaging, either positron emission tomography (PET) or computed tomography (CT), is routinely performed to observe the impact of systemic treatments on tumors, but the experience with surgery after treatment has shown some surprising findings.
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"CT scans and PET scans are underestimating the degree of tumor killing that we have with these new drugs, particularly with the targeted therapies," Dr. Sondak says.
According to Dr. Sondak, the future may see "surgical gene therapy" for patients who have multiple, unresectable metastases that are treated with targeted therapy or immunotherapy and in whom most tumors are stable or regressing but a single or a couple of tumors continue to grow. But the future may well see some patients who in the past would have absolutely required surgery, treated successfully entirely by medical means.
"It may be that some people will never need an operation," Dr. Sondak said. "That is an exciting prospect."
Disclosure: Dr. Sondak is a consultant to BMS, Merck, GSK, Amgen, Provectus and Novartis.
1 Sosman JA, Moon J, Tuthill RJ, et al. A Phase II Trial of Complete Resection for Stage IV Melanoma: Results of Southwest Oncology Group (SWOG) Clinical Trial S9430. http://www.ncbi.nlm.nih.gov/pubmed/21455999Cancer. 2011;117(20):4740-06