While higher doses of radiation therapy in patients with intermediate-risk prostate cancer lower the need for secondary therapies, the approach does not improve overall survival, results from a Phase 3 clinical trial show.

The study, “Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer,” was published in JAMA Oncology.

Optimizing radiation therapy for treatment of patients with localized prostate cancer can lead to better outcomes, as it has been shown to lower levels of prostate-specific antigen (PSA) — a marker of prostate cancer growth.

However, it is not known whether higher levels of radiation therapy improve overall survival in these patients. Therefore, researchers conducted the NRG Oncology/RTOG 0126 Phase 3 clinical trial (NCT00033631), which included 1,532 patients with intermediate-risk prostate cancer at centers across North America.

Patients were randomized to one of two radiation therapy regimens: either a higher dose of 79.2 gray — a standard measure of radiation — in 44 visits or the standard dose of 70.2 gray in 39 visits.

After a median follow-up of 8.4 years, there were no differences in overall survival between patients in the high dose group and patients in the standard dose group.

In fact, the eight-year rates of overall survival were 76% for patients in the high-dose group, compared with 75% in patients given the standard dose, which is not a statistically significant difference.

However, other parameters were affected by the higher radiation dose. The eight-year cumulative rates of distant metastases — the spread of cancer cells — were 4% for the high-dose group and 6% for the standard-dose group, a statistically significant difference. Similarly, while 35% of patients who received the standard dose experienced biochemical recurrence — a rise in PSA levels — eight years after treatment, only 20% in the high-dose group did.

“Our goal is to improve survival, but we didn’t see that despite advances in modern radiotherapy,” Jeff M. Michalski, MD, first author of the study and the Carlos A. Perez Distinguished Professor of Radiation Oncology at the Washington University School of Medicine, said in a press release. “But we did see significantly lower rates of recurrence, tumor growth and metastatic disease — tumors that spread — in the group that received the higher radiation dose. Still, that didn’t translate into better survival.”

Patients in the high-dose group also had lower rates of salvage therapy use, which refers to additional therapies used to control cancer cells from growing larger or spreading to other parts of the body. However, patients in the high-dose group also experienced higher toxicity, including urinary irritation or rectal bleeding, than those in the standard-dose group.

Since the higher dose is associated with lower metastases and reduced salvage therapy use, but also higher toxicity and no difference in overall survival, researchers suggest the choice of dose should be personalized to each patient.

“If we can safely deliver the higher dose of radiation, my opinion is to do that,” Michalski said. “It does show lower risk of recurrence, which results in better quality of life. But if we can’t achieve those ‘safe’ radiation dose goals, we shouldn’t put the patient at risk of serious side effects down the line by giving the higher dose. If we can’t spare the rectum or the bladder well enough, for example, we should probably back off the radiation dose. It’s important to develop treatment plans for each patient on a case-by-case basis.”