Resection of Metastatic Lesions Extends Survival in Multiple Tumor Types
Surgical oncologists urged other cancer providers to appreciate the potentially curative role that surgery can play in the management of many stage IV solid tumors, in a session during the American College of Surgeons 97th Annual Clinical Congress in San Francisco.
Stephen G. Swisher, MD, of The University of Texas MD Anderson Cancer Center, Houston, acknowledged there is no level 1 evidence for resecting pulmonary metastases. But since morbidity and mortality rates are very low, “the risk-benefit ratio is good, and even without level 1 evidence, you can argue for pulmonary metastasectomy,” he said.
When patients with colorectal cancer have pulmonary metastases in addition to liver metastases, this is not a poor prognostic factor or a contraindication to resection of liver metastases, he said. A recent review of the MD Anderson experience of 1,260 patients with colorectal cancer and liver-only or liver-plus-lung metastases found 5-year survival for the latter (50%) to exceed that of patients with liver-only metastases (40%; P = .01).1 The same investigators also reported that in patients with sarcoma, resection of both pulmonary and extrapulmonary lesions is associated with long-term survival.2
“We have been pushing the boundaries recently, and we see that long-term cure is possible after metastasectomy,” he said.
Dr. Swisher considers surgery in fit patients with no other curative options when the primary tumor is controlled and when complete resection of thoracic and extrathoracic metastases is possible. Complete resection, response to chemotherapy, disease-free interval > 24 months, number of nodules < 3, and germ cell histology are good prognostic factors.
For 1,225 patients with pulmonary metastasectomy in the MD Anderson Thoracic Surgery database, 3-year survival was 60%, 5-year survival was 46%, and 10-year survival was 28%.
Colorectal Liver Metastases
Yuman Fong, MD, of Memorial Sloan-Kettering Cancer Center, New York, advocated resection of colorectal metastases to the liver if an R0 resection can be safely performed.
He noted that the primary colorectal tumor and liver metastases can be safely resected during the same operation. Ablation is a potentially curable, liver parenchyma–sparing alternative to resection that can also be combined with resection.
“We can cure 20% of patients with metastatic colorectal cancer in the liver with surgery alone,” he said. “And more patients can be resected now because of our ability to downstage with neoadjuvant chemotherapy.”
The overall survival rate postresection is 60% at 5 years, and the 10-year disease-free survival rate is 20%.
While resectability used to be defined by number and size of lesions and presence of extrahepatic disease, it is now based on whether negative margins can be achieved and whether a liver remnant (> 20%) can be preserved.
“Neoadjuvant chemotherapy allows 15% of patients with initially unresectable disease to be converted to resectable status, but neoadjuvant chemotherapy is controversial, and most patients do not need it,” Dr. Fong added.
The absolute and relative indications for neoadjuvant chemotherapy can be a guide. Absolute indications are a dominant rectal tumor (bulky, very near the sphincter, or with nodal metastases, where there is a high risk of recurrence in the pelvis) and the need for medical optimization of the patient. Relative indications are a high clinical risk score based on a node-positive primary, disease-free interval < 12 months, presence of more than one tumor, size > 5 cm, and carcinoembryonic antigen level > 200 ng/mL.
Melanoma Metastatic to Distant Sites
“Surgery should be part of the multidisciplinary approach to metastatic melanoma. With medical treatment, the possibility of long-term survival after metastasis is rare. Resection of all metastatic sites can induce a complete clinical remission that may be durable for 5 to 10 years, and compared to the new targeted agents, surgery is also far less expensive,” said Donald L. Morton, MD, of John Wayne Cancer Institute, Santa Monica, California.
The low morbidity and mortality from surgery, improved staging, and the fact that 80% of patients have no more than three initial synchronous metastatic sites forms the rationale for cytoreductive surgery for metastatic melanoma, he said.
Prolonged survival (approximately 40% at 5 years and 20% to 30% at 10 years) was observed in resected stage IV disease in two large trials: a phase II trial evaluating the Canvaxin vaccine,3 and the phase III MMAIT-IV trial.4 The outcomes in these trials were far superior to those observed with trials of medical therapies, he noted.5 Survival is equally good for patients with two to three metastases vs one.
Reoperation for recurrent disease postresection yields a median survival exceeding 17 months and a 5-year survival of almost 20%, compared with < 6 months and a 2% survival at 5 years for patients who do not undergo surgery, Dr. Morton noted. A trial of surgery vs nonsurgical treatment of stage IV melanoma is being proposed.
Metastatic Breast Cancer
Approximately 50% of patients with metastatic breast cancer receive some form of local therapy, said Seema Khan, MD, of Northwestern University Feinberg School of Medicine, Chicago.
This is surprising but may be occuring for several potential reasons: Women who have favorable features such as young age, small tumor size, hormone receptor–positive disease, or low volume of metastatic disease may selectively be offered surgery more frequently. It is also possible that an intact primary tumor can be the source of new metastatic lesions, may not respond to systemic therapy in parallel with metastatic sites, (which can lead to uncontrolled chest wall disease), and may serve as a continued source of tumor stem cells that seed new chemotherapy-resistant lesions, Dr. Khan noted.
The possible benefit of primary tumor resection can be seen in a growing body of data. In numerous studies, resection of the primary is associated with a mortality reduction of 30% to 40%, and 3-year survival rates improve by an absolute 16% to 20%, she said.
Response to systemic therapy prior to surgery is a good prognostic factor, she added.
“It is possible that primary site therapy, which should be thought of as a combination of surgery and radiotherapy, will prolong survival in stage IV breast cancer, but this is still a hypothesis and needs to be demonstrated in prospective trials,” said Dr. Khan, who is heading up E2108, which will enroll women with intact primary tumors and metastatic disease. In the trial, a period of induction systemic therapy will be followed by randomization to the standard of care (continuation of systemic therapy with local therapy used only if needed for palliation of symptoms) or full local therapy for the primary site as is practiced in the non-metastatic setting. ■
Disclosure: Dr. Morton was an independent contractor, consultant, board member, and stock owner for CancerVax Corporation, the company that produced Canvaxin, the investigational agent in the MMAIT trials. Dr. Khan reported no potential conflicts of interest.
1. Brouquet A, Vauthey JN, Contreras CM, et al: Improved survival after resection of liver and lung colorectal metastases compared with liver-only metastases: A study of 112 patients with limited lung metastatic disease. J Am Coll Surg 213:62-69, 2011.
2. Blackmon SH, Shah N, Roth JA, et al: Resection of pulmonary and extrapulmonary sarcomatous metastases is associated with long-term survival. Ann Thorac Surg 88:877-884, 2009.
3. Hsueh EC, Morton DL: Antigen-based immunotherapy of melanoma: Canvaxin therapeutic polyvalent cancer vaccine. Semin Cancer Biol 13:401-407, 2003.
4. Morton DL, Mozzillo N, Thompson JF, et al: An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites. MMAIT Clinical Trials Group. J Clin Oncol 25(18 suppl):Abstract 8508, 2007.
5. Korn EL, Liu P-Y, Lee SF, et al: Meta-Analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 26:527-534, 2008.