Does ADT Plus Radiation Improve Survival in Metastatic Prostate Cancer?

Gerald Chodak, MD


November 13, 2018

Hello. I'm Dr Gerald Chodak for Medscape. Today's topic is debulking the primary tumor in men with metastatic prostate cancer, in the context of a new European study.

From 2004 to 2014, Boeve and colleagues[1] randomly assigned 432 men to receive either androgen deprivation therapy (ADT) alone or ADT in combination with external radiation therapy. Men who were enrolled had a median PSA of 142 ng/mL, and two thirds had more than five bone metastases. They could have any T stage and any Gleason score at enrollment. The ADT consisted of 1 month of an antiandrogen in combination with luteinizing hormone-releasing hormone (LHRH) therapy throughout the study. The radiation was the equivalent of 70 Gy. So far, the men have been followed for 47 months and overall survival is not statistically significantly different between the groups: 45 months in the combination-therapy group and 43 months in the ADT-alone group.

Other, uncontrolled trials have suggested a benefit from combining the two therapies. But here again we see the importance of making decisions based on evidence from a randomized controlled trial (RCT) rather than an uncontrolled trial. Something similar happened in breast cancer, where uncontrolled trials suggested a benefit from debulking the primary tumor; however, this benefit disappeared in RCTs.

Certain limitations may have had some impact on the study outcome. First, men did not receive radiation to the lymph nodes. Second, the 70-Gy dose of radiation is lower than is currently used. The higher doses have not clearly proven a survival benefit, however—only a biochemical disease-free survival benefit. Third, and perhaps most important, we now know that men who have metastatic disease and bulky metastatic disease may benefit from early chemotherapy in combination with ADT, and that was not used here. Finally, the men in this trial did not receive a standardized form of therapy when their disease progressed.

Nevertheless, this is a well-done RCT. It is important for us to realize that without these randomized trials, false or incorrect conclusions may result. We do have ongoing RCTs assessing the potential value of debulking with surgery. But outside of participating in one of those trials, I feel quite strongly that it would be wrong to administer combination therapy for debulking the primary tumor.

I look forward to your comments. Thank you.


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