Primary androgen deprivation therapy linked to lower survival in American men

Okayama, Japan-Primary androgen deprivation therapy for localized prostate cancer is associated with significantly better survival outcomes in a Japanese cohort compared with an American population, according to a recent study.

The reasons why Western and Asian prostate cancer treatment guidelines differ in their recommendations on use of primary androgen deprivation therapy (pADT) for localized disease are multifactorial, but the appropriateness of the discrepancy has not been clear. The findings of the study, presented at the AUA annual meeting in San Diego, support the disparate recommendations of the different guidelines, according to investigators.

Trans-Pacific variation in outcomes for men treated with pADT for prostate cancer was investigated in a collaborative study using data from 16,300 men included in the Japan Study Group of Prostate Cancer (J-CaP) and 1,934 men registered in the U.S. Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database. In a multivariate analysis adjusting for multiple factors, including age, disease risk, year of diagnosis, type of androgen ablation, and treatment setting, the Japanese cohort had a threefold lower prostate cancer-specific mortality hazard compared with the American men.

“Guidelines from the American Urological Association, National Comprehensive Cancer Network (NCCN), and the European Association of Urology do not endorse pADT as monotherapy for localized prostate cancer, except in rare cases. However, it is described as an option by the NCCN Asian Consensus panel and by the Japanese Urological Association guidelines,” said co-author Shiro Hinotsu, MD, associate professor, Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.

“Prior studies focusing on populations on either side of the Pacific have reported disparate outcomes for pADT. We now confirm this difference in a direct comparison study,” said Dr. Hinotsu, whose institution collaborated on the study with Peter R. Carroll, MD, MPH, and Matthew R. Cooperberg, MD, MPH, of the University of California, San Francisco.

Disease risk for men included in the study was described using the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, a novel risk assessment system that the investigators had previously developed and validated. J-CAPRA calculates a risk score ranging from 0 to 12 by assigning points for PSA level, Gleason score, T stage, and the presence of nodal positive and metastatic disease.

Distributions of J-CAPRA scores showed that higher proportions of U.S. men compared with the Japanese cohort were in a low-risk category (J-CAPRA 0 to 2), while more Japanese men had scores in the higher risk range. The mean J-CAPRA score was significantly lower for the American men compared with the Japanese men (3.0 vs. 2.1).

There were also statistically significant differences between the U.S. and Japanese populations in mean age and type of ADT received. Compared with the Americans, the Japanese men were older (75 vs. 73 years) and more likely to have received combined androgen blockade (67% vs. 45%).

5-year mortality higher for Americans

In an unadjusted analysis in which men were stratified into three risk categories based on J-CAPRA score, 5-year cancer-specific mortality rates were consistently higher for the Americans compared with their Japanese counterparts in all subgroups. For example, looking at the intermediate-risk groups (J-CAPRA 3 to 7), the mortality rates were 10% to 15% lower for the Japanese men, noted Dr. Hinotsu.

He observed that the etiology for the trans-Pacific difference in survival outcomes of men treated with pADT for localized prostate cancer is unclear, although Dr. Hinotsu offered several possible explanations.

“Differences in genetics, diet, lifestyle, or environmental exposures may play a role. Additionally, there may be unmeasured confounding factors not captured by the J-CAPRA risk score,” Dr. Hinotsu said.

“However, better understanding of these differences is important as the information may provide novel insights into varying biology of prostate cancer on both sides of the Pacific.”UT

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