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Should surgery dominate as the standard of care for mesothelioma or be in reserve for a select group of pts?

Should surgery dominate as the standard of care for mesothelioma or be in reserve for a select group of pts?

Surgical intervention for mesothelioma has become widely accepted, but controversy persists: Should surgery be the standard of care or should it be offered only to select patients? According to scientific literature, surgery decreases morbidity and mortality while also improving outcomes compared with adjunctive therapy alone.

The merits of surgery for mesothelioma were debated at the 2009 World Conference on Lung Cancer in San Francisco by David J. Sugarbaker, MD, chief of the division of thoracic surgery at Brigham and Women’s Hospital in Boston, and Nick Pavlakis, PhD, head of the department of medical oncology at the Royal North Shore Hospital in Sydney, Australia.

Surgery for long-term survival
Surgery for mesothelioma, particularly extrapleural pneumonectomy, decreases the risk of local failure and metastases and allows for cytoreduction that enhances the effectiveness of adjunctive therapies, according to Dr. Sugarbaker. Thus it improves survival in mesothelioma patients, he said. Surgical resection also allows the most accurate pathologic staging and will soon be paired with genomic classification of tumors, enabling clinicians to target therapies to individual patients, Dr. Sugarbaker said. “What are the advantages of surgery? It allows cytoreduction and extrication or resection of primary disease, as well as control of micrometastatic disease,” Dr. Sugarbaker said. In addition to relieving symptoms, surgery can help optimize adjuvant therapy, providing mesothelioma patients with the best chance for survival, he said.

Many studies have shown improved survival of patients who undergo extrapleural pneumonectomy or pleurectomy/decortication. An analysis of outcomes in 945 patients showed that those who had undergone surgery had improved outcomes, although tumor histology, asbestos exposure, and other factors predicted survival as well. Multimodality therapy was associated with a median survival of 20.1 months (J Thorac Oncol 2:237-242, 2007).

By contrast, studies that have analyzed single-modality therapies without surgery have shown median patient survival of 12 months or less. A phase III study of 456 mesothelioma patients treated with pemetrexed (Alimta) in combination with cisplatin compared with cisplatin alone showed a survival of 5.7 months in the pemetrexed/cisplatin arm and a survival of only 3.9 months in the cisplatin arm, Dr. Sugarbaker noted (J Clin Oncol 21:2636-2644, 2003).

Surgery reduces the potential sites for recurrence, which is an important consideration, since local failure is the most important barrier to long-term survival in mesothelioma patients. “Macroscopic complete resection is the goal in mesothelioma surgery, and if you can leave patients with zero visible disease, that’s not bad,” Dr. Sugarbaker said.

Removal of the tumor in mesothelioma surgery also allows the most accurate pathologic staging, which helps clinicians select the best adjunctive therapies for their patients, Dr. Sugarbaker noted. He also said that the need for tissue samples is growing with the ability to study tumor genomics, and scientists will soon be able to target therapy based on genetic profiles of individual tumors. Instead of debating the merits of surgery, clinicians should be focused on how to target adjunctive therapy to best prevent recurrence, Dr. Sugarbaker said. He noted significant advances in understanding the genetics of mesothelioma. A recent study found that a ratio based on expression of four genes in the tumors of 120 patients was a significant factor that distinguished between patients at low risk and those at high risk for recurrence (J Natl Cancer Inst 101:678-686, 2009).

Surgery relieves symptoms in many patients and improves quality of life. Complication rates from surgery have also decreased greatly in the past 20 years, Dr. Sugarbaker said.

Most important, surgery offers patients their best shot at improved survival, especially when combined with adjunctive therapies. “That’s the Holy Grail: having long-term survivors,” he said.

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