NCCN MESOTHELIOMA GUIDELINESS

March 17, 2010 (Hollywood, Florida) — The National Comprehensive Cancer Network (NCCN) has issued its first-ever guideline on mesothelioma. The new document was presented here at the NCCN 15th Annual Conference by Lee M Krug, MD, from Memorial Sloan-Kettering Cancer Center in New York City.

Dr. Krug said that the guideline was "challenging to prepare," in part, because there are few "data available."

"It should be exciting to see how this evolves over time," he noted.

Robert Morgan, MD, from the City of Hope Cancer Center in Los Angeles, California, said that it is "the first time a comprehensive mesothelioma guideline has been assembled by any organization." Dr. Morgan is not part of the NCCN mesothelioma panel.

With only about 2000 cases a year in the United States, mesothelioma is a rare disease, said Dr. Krug.

Nevertheless, it was featured in the mainstream media just as the NCCN meeting started because former National Football League star Merlin Olsen died at the age of 69 from complications related to the disease.

Dr. Krug offered a quick disease profile: mesothelioma arises from parietal pleura, peritoneum, tunica vaginalis testis, or pericardium and is more than 4 times more common in men. Asbestos exposure is a risk factor, with a latency of more than 20 years, but the exposure might require predisposition, said Dr. Krug. Mesothelioma can also occur after radiation exposure, such as for the treatment for Hodgkin's disease.

The diagnosis is difficult. It is often missed on pleural fluid cytology and often requires surgical biopsy, said Dr. Krug.

The subtypes are epithelioid (about 80% of cases), sarcomatoid (which rarely responds to chemotherapy), or mixed.

Two serum markers — soluble mesothelin-related protein and osteopontin — have been detected at higher levels in mesothelioma patients than in control subjects. It is not known whether this will translate into a screening test, said Dr. Krug. The markers are also being evaluated for prognostic significance and their role in monitoring disease status.

Staging and Treating

Mesothelioma typically presents with disease confined to the ipsilateral pleura, said Dr. Krug.

For staging guidance, clinicians should review parameters established by the International Mesothelioma Interest Group, he noted.

As part of pretreatment evaluation, the NCCN recommends FDG-positron emission tomography; the scan will find metastases in about 10% of cases.

For stage I to III disease, surgery is recommended for patients who are fit and pass a cardiac stress test.

There are 2 types of surgery: pleurectomy/decortication, which is a debulking procedure and has relatively low morbidity and mortality; and extrapleural pneumonectomy, which is considered to be "more aggressive," said Dr. Krug.

"The role of aggressive surgery is controversial," he said.

Extrapleural pneumonectomy consists of the removal the of pleura, lung, diaphragm, and pericardium. "Of course, it is associated with more major complications," said Dr. Krug, adding that they occur in 20% to 40% of cases. Nevertheless, the mortality rate is only 6% at Memorial Sloan-Kettering Cancer Center. "Only experienced surgeons should perform" this procedure, added Dr. Krug.

During the Q&A session following the presentation, a physician who said he was from a "shipbuilding" community with workers exposed to asbestos asked if even the best surgical results (clear margins, no visible evidence of disease) provided a survival advantage over other treatment approaches, including those with chemotherapy and radiation.

"I've been waiting for that question," responded Dr. Krug. "It's not clear if surgery offers a survival advantage."

Nevertheless, experts believe that "if you have a fit patient with resectable mesothelioma, evaluation for surgery is reasonable."

"Surgery alone is inadequate treatment," Dr. Krug said, "because it is very likely that microscopic disease is left behind." Chemotherapy and radiation are also used, often in a trimodality approach.

In one study in the United States, patients who underwent and completed all 3 forms of treatment had a median survival of 29.1 months, compared with 16.8 months for patients who did not complete all of the treatment. "It helps to have all the treatment completed," said Dr. Krug.

Whether chemotherapy should be given prior to or after surgery remains unclear. Different centers have different approaches," Dr. Krug said.

Pemetrexed and cisplatin combination therapy is the standard first-line regimen.

In one phase 3 study, this combination plus vitamin supplementation provided a median survival time of 13.3 months and a 1-year survival rate of 57%.

Gemcitabine is a "reasonable alternative" to pemetrexed for use in combination with cisplatin for patients who may not tolerate pemetrexed because of poor renal function or other reasons, said Dr. Krug.

Radiation is limited to use as an adjuvant after surgery or as palliative therapy.

It is difficult to radiate pleura with the lung intact without causing pneumonitis. "It's like trying to shoot the peel off an apple without damaging the apple," said Dr. Krug, relaying a colleague's comment.

Dr. Krug has disclosed no relevant financial relationships.

National Comprehensive Cancer Network (NCCN) 15th Annual Conference: Presented March 13, 2010