Radiotherapy Dose Escalation Ups Survival in Some Prostate Cancer Patients

SAN FRANCISCO—Radiotherapy dose escalation is critical to improving survival in some patients with prostate cancer, according to a study presented at the 43rd Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 247). In the study, patients were followed for 8 to 12 years after treatment.

"By cranking up the dose 5% to 6%, we can increase survival by 50% in some patients," said lead researcher Gerard E. Hanks, MD, retired chairman of the radiation oncology department at Fox Chase Cancer Center.

In the study, which took place between 1989 and 1992, more than 200 patients with varying PSA levels—most greater than 10 ng/mL—received escalating doses of radiation therapy ranging from 68 Gy to 79 Gy.

The study is one of the first to examine long-term response to radiation therapy. "We’re always talking about not having long-term data in radiation oncology," Dr. Hanks said. "This study gives us one of the first measures of long-term survival. It affords an opportunity to better understand dose response, side effects, and the long-term effects of dose escalation, such as reducing metastasis rates."

Of the 232 patients, three were not available for follow-up. Sixty-nine patients are living cancer-free, 54 living patients have had PSA failure, and 8 patients have had metastasis. Seventeen patients have died of prostate cancer, and 81 have died of other causes.

To analyze the effect of radiation dose on survival, the researchers divided the patients into three groups according to initial PSA level—PSA under10 ng/mL, PSA 10 to 19.9 ng/mL, and PSA over 20 ng/mL.

The patients in each category were then divided into a favorable and unfavorable group, based on prognostic indicators at the beginning of treatment. Those in the unfavorable groups had bifocal disease and a Gleason sum of 7 or higher.

Dose response for PSA failure at 5 years was evaluated using logit response models. Multivariate analysis was based on the Cox proportional hazards model.

The results indicated that higher radiotherapy doses were critical for survival in the low-PSA unfavorable group and in the intermediate-PSA favorable and unfavorable groups. "Treatment success is improved by approximately 40% and distant metastases are reduced significantly for those patients with an initial PSA of 10 to 19.9 ng/mL (P = .05)," Dr. Hanks said. With enough patients and time, these results will translate into improved survival, he added.

Some Patients Cured

Dr. Hanks said that the 69 patients who are now living cancer free should be regarded "as absolutely, positively cured." He cautioned, however, that the previously observed dose response in the high-PSA group has diminished as the study has continued and more patients have failed.

Dr. Hanks recommends that patients with a PSA less than 10 ng/mL and unfavorable prognostic indicators should be treated with a minimum of 75 Gy of radiation therapy. Those with favorable and unfavorable prognostic indicators and a PSA of 10 to 19.9 ng/mL should be treated with a dose that is greater than 75 Gy. Raising treatment dose to 75 to 80 Gy is one of the most important goals for national practice, he concluded.