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Higher doses of radiation don't improve overall survival for prostate cancer patients

Side effects more common with higher doses but patients on standard dose more likely to need further therapies

Ingrid Torjesen

Friday, 16 March 2018

Higher doses of radiation do not improve overall survival for patients with prostate cancer, compared with the standard radiation treatment, an analysis* published in JAMA Oncology has shown.

The study included around 1,500 patients with intermediate-risk prostate cancer, meaning the patient had a PSA score of 10-20 ng/ml and a Gleason score of two to seven, or a Gleason score of seven and PSA of less than 15.

Half the patients received a standard radiation dose of 70.2 Gy delivered over 39 treatment visits, and half received increasing doses up to 79.2 Gy delivered over 44 visits.

Of the 748 men receiving standard treatment, 75% were still alive after eight years of follow-up. Of the 751 men receiving the dose-escalation treatment, 76% were alive at the eight-year mark - a difference that is not statistically significant. These overall survival rates included deaths for any cause, not just those due to prostate cancer.

Over the course of the study, 51 patients died of prostate cancer, which is 3.4% of all patients enrolled. At the eight-year mark, the death rate due to prostate cancer for patients receiving standard treatment was 4% compared with 2% for patients receiving the escalating dose. These rates also were not statistically different.

Patients in the standard dose group were more likely to undergo further therapies to control tumours that had grown larger or that had spread to another site in the body. But patients in the escalating dose group experienced more side effects, such as urinary irritation or rectal bleeding, sometimes years after treatment.

Researcher Dr Jeff M. Michalski, the Carlos A. Perez Distinguished Professor of Radiation Oncology at the Washington University School of Medicine in the US, said: "Our goal is to improve survival, but we didn't see that despite advances in modern radiotherapy." He continued, "But we did see significantly lower rates of recurrence, tumour growth and metastatic disease -- tumours that spread -- in the group that received the higher radiation dose. Still, that didn't translate into better survival. The patients in the trial did better than we anticipated, and part of that may have been because of improvements in metastatic cancer therapy over the 10 years of the trial."

During the 10 years it took to enrol enough patients in the trial, at least six new therapies were approved for recurrent or metastatic prostate cancer, and these therapies have been shown to improve survival. It is possible the patients in the standard treatment arm, who were shown to need more follow-up therapies, would not have done as well as the group receiving the escalating dose had these new therapies not become available, he said.

"Of course, these additional therapies have their own side effects, as does the higher initial dose of radiation therapy. In addition, the selective use of androgen withdrawal therapy has been shown to improve survival in men treated with radiation therapy. This treatment can be combined with either standard or higher dose radiation therapy," Dr Michalski said.

"If we can safely deliver the higher dose of radiation, my opinion is to do that," he added.

"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."

*Michalski JM, Moughan J, Purdy J, et al. Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate CancerThe NRG Oncology RTOG 0126 Randomized Clinical Trial. JAMA Oncol. Published online March 15, 2018. doi:10.1001/jamaoncol.2018.0039

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