First-year weight loss with androgen-deprivation therapy increases risks of prostate cancer progression and prostate cancer-specific mortality: results from SEARCH

44 Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We successfully genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS<7. After a median follow-up of 1.8 years (IQ range: 0.8–3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table . Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. [Table: see text] No significant financial relationships to disclose.

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Androgen Deprivation Therapy Use in the Setting of High-Dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2016.06.338 ◽

2016 ◽

Vol 96 (2) ◽

pp. S139

Author(s):

B. Rose ◽

M.H. Chen ◽

J. Wu ◽

M.H. Braccioforte ◽

B.J. Moran ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

High Dose ◽

Specific Mortality ◽

Cancer Specific Mortality ◽

Competing Mortality ◽

Dose Radiation

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Effectiveness of Primary Androgen-Deprivation Therapy for Clinically Localized Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2013.52.5782 ◽

2014 ◽

Vol 32 (13) ◽

pp. 1324-1330 ◽

Cited By ~ 50

Author(s):

Arnold L. Potosky ◽

Reina Haque ◽

Andrea E. Cassidy-Bushrow ◽

Marianne Ulcickas Yood ◽

Miao Jiang ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Localized Prostate Cancer ◽

Curative Intent ◽

Primary Androgen Deprivation Therapy ◽

All Cause Mortality ◽

Specific Mortality ◽

Cancer Specific Mortality ◽

Primary Androgen Deprivation

Purpose Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions. Methods We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis. Results Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer–specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer–specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97). Conclusion We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.

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