A University of Rochester Medical Center study challenges treatment guidelines for early stage follicular lymphoma, concluding that six different therapies can bring a remission, particularly if the patient is carefully examined and staged at diagnosis.

The research underlines the fact that when cancer strikes, modern patients and their oncologists across the United States are taking many diverse treatment paths when there is scant data to support one method over another. This study suggests that the old standard approach -- radiation therapy, alone -- is no longer the best choice for early follicular lymphoma, according to researchers at the James P. Wilmot Cancer Center at URMC, published in the Journal of Clinical Oncology.

Lead author Jonathan W. Friedberg, M.D., acting director of the Wilmot Cancer Center and chair of Hematology/Oncology at URMC, pointed out that the earlier recommendation for radiation was based on uncontrolled experiences at select institutions.

"As we move into an era focused on quality, we need research like this to help us determine the true effectiveness of various therapies when definitive studies are lacking," Friedberg said. "The choice of treatment should be based on whether it produces remission and survival. And if the outcomes are equivalent, then we'll need to consider toxicities and tolerance of therapies, as well as cost. We hope our data will assist physicians in making decisions with patients."

Researchers followed 471 patients for up to 10 years. The study is believed to be the largest of early-stage follicular lymphoma (FL) in the modern treatment era.

All patients were identified through a disease registry called National LymphoCare, which includes more than 2,700 cases diagnosed between 2004 and 2007, at 200 medical practices in the U.S.

As the definition of stage 1 FL changed over time, so did the way doctors evaluated and diagnosed patients. Two groups emerged in the study: People who received a comprehensive staging exam, which included imaging tests and a bone marrow biopsy, and people who were not carefully staged. The latter group had more recurrences and individuals were less likely to survive. This finding emphasizes the importance of a rigorous evaluation at diagnosis as the best way to predict the prognosis, Friedberg said.

Among all patients, researchers observed six treatment approaches, from a conservative watch-and-wait strategy to an aggressive combination of chemotherapy and radiation.

An important goal of the Wilmot study was to better understand the outcomes associated with the various treatment options, since no data so far has proven that one therapeutic approach is better than another for early-stage FL. Researchers noted that only 34 percent of patients with stage 1 FL were treated with the recommended radiation therapy, according to their analysis of the national cancer database.

Of the 206 patients who were carefully staged, a greater percentage also chose more aggressive therapy, such as an immunotherapy-chemotherapy combination (28 percent versus 17 percent of non-rigorously staged patients) or chemo and radiation (13 percent versus 6 percent non-rigorously staged patients).

Although the overall survival outcomes were the same for both groups, the patients who were most carefully evaluated at diagnosis had superior progression-free survival, which means the cancer did not relapse as often. (FL is characterized by frequent relapses, even if treatment controls the relapses.) During a median follow-up of 57 months, 21 percent of the staged patients experienced FL progression.

An estimated 66,000 people in the U.S. were diagnosed with non-Hodgkin lymphoma in 2011. Follicular lymphoma is the most common form of non-Hodgkin lymphoma. Most often it occurs in older people. FL is usually slow-growing; an early symptom is lymph node enlargement. Although not curable, the median five-year survival rate is about 75 percent and patients can live for many years, even after relapses. Approximately 26 percent of people who have FL are diagnosed at stage 1.

Genentech funded the research. The drug company, a member of the Roche Group, makes Rituxan (rituximab), approved by the U.S. Food and Drug Administration in 1997as the first therapeutic antibody for cancer. It is often indicated for follicular lymphoma. Additional funding came from the National Cancer Institute SPORE grant, which supports a lymphoma research partnership between the URMC and University of Arizona Cancer Center.