The Influence of previous hormone therapy on PSA response In prostate cancer patients (PTS) failing first-line androgen ablation

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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Predictive value of bone scan index using computer-aided diagnosis system for bone scans in patients receiving first-line hormone therapy for metastatic hormone-sensitive prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.225 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 225-225

Author(s):

Yasuhide Miyoshi ◽

Masato Yasui ◽

Shuko Yoneyama ◽

Koichi Uemura ◽

Takashi Kawahara ◽

...

Keyword(s):

Prostate Cancer ◽

Hormone Therapy ◽

Survival Benefit ◽

Bone Scan ◽

First Line ◽

Bone Scan Index ◽

Computer Aided ◽

Hormone Sensitive ◽

Bone Scans ◽

Aided Diagnosis

225 Background: Recently, the CHAARTED and STAMPEDE studies showed a survival benefit for docetaxel when started with androgen deprivation therapy (ADT) in men with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). While GETUG-AFU 15 failed to demonstrate a survival benefit of early chemotherapy. New biomarker for select the candidate for early chemotherapy in mHSPC is warranted. The objective of this study is to evaluate the bone scan index (BSI) using computer-aided diagnosis system for bone scans for predictive factor in patients receiving ADT as first-line hormone therapy for mHSPC. Methods: We identified consecutive 85 mHSPC patients treated with maximum androgen blockade (MAB) as first-line hormone therapy. We analyzed the correlations between progression-free survival (PFS) of MAB and clinicopathological characteristics, including patients’ age, initial PSA levels, Gleason scores, clinical TNM stage, hemoglobin (Hb), lactase dehydrogenase (LDH), c-reactive protein (CRP), and bone scan index (BSI). Statistical analyses were assessed using cox proportional hazards regression models. Results: The median patients’ age was 73 and the median follow-up duration was 11.3months. The median initial PSA value was 270 ng/ml. Median BSI was 2.7 % (range: 0.0-14.6). Clinical or PSA progression occurred in 55 (64.7%) patients. The median time to progression was 12.9 months. In multivariate analysis, three significant risk factors for PFS were identified; patients’ age ( > 73 years old vs ≤ 73; HR 0.53, p = 0.038), initial PSA levels ( > 270 ng/mL vs ≤ 270; HR 0.53, p = 0.038), and BSI ( > 2.7 vs ≤ 2.7; HR 3.0, p < 0.000). We stratified the patients into two cohorts with low risk (0-1 risk factor present) and high risk (2-3 risk factors present). We found a significant difference in PFS among risk groups (median PFS 15.3 months vs 8.5, p < 0.000). Conclusions: Patients’ age, initial PSA levels, and bone scan index were the significant predictive factors for MAB as first-line hormone therapy in patients with mHSPC. These findings might support the decision-making of induction of early chemotherapy for mHSPC.

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Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer (mCRPC): The prostate cancer registry.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.212 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 212-212 ◽

Cited By ~ 2

Author(s):

Simon Chowdhury ◽

Alison J. Birtle ◽

Anders Bjartell ◽

Luis Costa ◽

Susan Feyerabend ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Registry ◽

Real World ◽

Severe Disease ◽

Specific Antigen ◽

Abiraterone Acetate ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Psa Response ◽

Baseline Characteristics

212 Background: The Prostate Cancer Registry is the first prospective, international observational study in mCRPC documenting characteristics and management in routine clinical practice, independent of treatment used. The study began in June 2013 enrolling > 3000 mCRPC patients (pts) followed for ≤ 3 years. Methods: Source-verified data were collected from men with documented mCRPC initiating a new mCRPC treatment or in surveillance. A history of disease progression despite surgical or chemical ADT was confirmed in all pts. This interim analysis reports baseline characteristics, treatments and outcomes in pts with no prior mCRPC treatment. To evaluate comparative effectiveness between treatments, propensity scoring (PS) methods were used to reduce effects of confounding. Results: Of 1906 evaluable pts with ≥ 12-month follow-up, the most commonly initiated first-line mCPRC treatments (n ≥ 50) were abiraterone acetate + prednisone (AA, n = 472), enzalutamide (ENZ, n = 98) or docetaxel (DOC, n = 382). Baseline characteristics, time to progression (TTP) and prostate-specific antigen (PSA) response ( ≥ 50% decrease within 6 months) are shown in the table below. Conclusions: In this real-world study, pts receiving DOC as their first mCRPC treatment had more severe disease at entry and a trend for shorter TTP vs androgen inhibitors. TTP results are consistent with those in randomised clinical trials for AA and ENZ. Clinical trial information: NCT02236637. [Table: see text]

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