CHICAGO (June 30, 2014): Surgical resection markedly improves survival among metastatic melanoma patients whose disease is isolated to a few areas in the liver, according to new study findings published in the July issue of the Journal of the American College of Surgeons. These results mark a departure for melanoma, an aggressive form of skin cancer, that is most often considered fatal once it has spread to the liver and then, not amenable to surgical treatment.
In the past, surgical treatment for liver metastases was not considered an option for most patients, as the disease typically spreads to other organs. However, advances in surgical techniques along with new systemic therapies have made existing therapies more effective and opened the door to new therapeutic approaches.
"Although there has been a great deal of excitement about the new medical therapies, which are clearly enormous advances, those are still not the answers for everyone," said lead investigator Mark Faries, MD, FACS, Director of the Donald L. Morton, MD, Melanoma Research Program at John Wayne Cancer Institute in Santa Monica, Calif. "We've been proponents of metastasectomy for a long time and wanted to know how our patients who had been treated surgically for liver metastases had done."
For the study, Dr. Faries and colleagues studied medical records of 1,078 patients who had been treated for melanoma liver metastases at their center since 1991. Of those, 58 were treated surgically with liver resection, an operation that removes the cancerous portion of the liver. In some cases, surgical treatment included local ablation therapy in addition to resection. Ablative treatments such as radiofrequency ablation or microwave ablation are used to destroy tumors in patients who are not able to have all of their metastases surgically resected.
Median overall survival among patients who underwent surgical resection was more than triple that of patients who received medical therapy without surgical treatment (24.8 months vs. 8 months). The five-year survival rate for surgical patients was 30 percent, compared with 6.6 percent for the nonsurgical group.
"What we have seen in previous studies is that many patients who are able to undergo resection of their metastatic disease from melanoma can have good long-term outcomes, which is important to remember even in an era of more effective medications," Dr. Faries explained.
Median overall survival was similar among patients undergoing ablation (with or without resection) compared with those undergoing surgical treatment alone. The promising news is that newer technologies such as ablation may enable more metastatic melanoma patients to have surgical treatment, according to Dr. Faries.
The investigators also looked at the relationship between systemic therapy and surgical treatment. According to study authors, when patients had had their metastatic disease stabilized with systemic therapy--meaning their metastatic disease either shrank or stopped growing significantly as a result of medical therapy--and then underwent a surgical treatment, the patients whose disease had been stabilized prior to the operation did much better over the long term than those who did not have their metastatic disease stabilized.
"The presence of more effective medications may, in fact, make surgical treatment more important or may lead to new approaches that combine liver resection with these more effective medications, which may result in even better outcomes than any individual therapy alone," Dr. Faries said.
He thinks that what holds promise for the future is the potential to combine systemic therapy with local surgical or ablative therapies. For instance, patients would undergo systemic therapy for a defined period of time and then undergo resection. "This approach could apply to liver metastases as well as metastases in other places in the body," he said. "That path would give surgeons the opportunity to more appropriately select patients for surgical treatment and to assess their response to the new drugs."
Study limitations include the fact that the investigation was a retrospective study spanning two decades, which means researchers were unable to control for certain factors. Additionally, since isolated liver metastases are rare in melanoma, the vast majority of the metastatic melanoma population would not be candidates for surgical resection.
"In our recent study, the fraction of patients that was able to undergo resection was higher than it had been in previous studies," Dr. Faries said. "It is only about 1 in 20 patients that ended up being able to have the operation, but that number is still higher than it used to be."
The bottom line, according to Dr. Faries, is that surgeons should discuss surgical resection for the treatment of melanoma liver metastases with their patients if their disease is limited to a few areas in the liver, their overall health status is good, and the disease is indolent or the patients are responding to systemic therapy.
Other study authors include Anna Leung, MD; Donald L. Morton, MD; Danielle Hari, MD; Ji-Hey Lee, PhD; Myung-shin Sim, PhD; and Anton J. Bilchik, MD, PhD, FACS.
This study was supported by grant P01CA29605 from the National Cancer Institute, Dr Miriam & Sheldon G Adelson Medical Research Foundation (Boston, MA), Borstein Family Foundation (Los Angeles, CA), The California Oncology Research Institute (Los Angeles, CA), and the John Wayne Cancer Institute Auxiliary (Santa Monica, CA). Dr. Leung was the Harold McAlister Charitable Foundation Fellow (Los Angeles, CA). Dr. Hari was the William Randolph Hearst Foundation Fellow (San Francisco, CA). Content is solely the responsibility of the authors and does not necessarily represent the official view of the National Cancer Institute or the National Institutes of Health.
Citation: Journal of the American College of Surgeons, July 2014: Vol. 219 (1) 62-68.
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