The effect of statins on overall survival and progression-free survival in veterans with prostate cancer: A retrospective single-center experience.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 169-169
Author(s):  
Brian Warnecke ◽  
Raissa Lakene Djoufack Djoumessi ◽  
Juan Garza ◽  
Michael Mader ◽  
Shreya Chaudhary ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
The United States ◽  
Inverse Association ◽  
Free Survival ◽  
End Point ◽  
Anti Cancer ◽  
Statin Use

169 Background: Prostate cancer is the most common cancer in men in the United States. Death in prostate cancer patients is often related to other medical conditions and not prostate cancer itself. Hence, it is important to optimize other co-morbidities, such as hyperlipidemia, hypertension, and cardiovascular diseases in these patients. However, there are numerous studies portraying the ability of statins to increase progression free survival and overall survival of prostate cancer. This has led to significant interest of statins having anti-cancer properties and ultimately improving long term outcomes. Methods: This is a retrospective observational study with chart review of 1,011 patients diagnosed with prostate cancer from 1995 to 2010 in a VA Hospital in San Antonio, Texas. Variables included age at diagnosis, statin use, type of statin (1st, 2nd, or 3rd generation), dose of statin (4 dosage levels), length of statin use, time followed in months (from diagnosis to death or end of study period), death, cause of death, and time to first progressive disease. Progressive disease was defined using PSWG2 guidelines which is PSA increase > / = 25% and at least 2ng/dl above the nadir. The Cox proportional hazards regression model was used to estimate the hazard function, with age, co-morbities and other cancers used as a covariate. End points were death by prostate cancer (56), death by any cancer (140), and death by all causes (484). We also looked at the effects of statins on progression free survival of prostate cancer. Results: The hazard ratio (HR) for use of statins and death by prostate cancer was 0.35, 95% confidence interval (CI): 0.20-0.62 (p = 0.0003), indicating that statin use has a statistically significant positive effect at delaying death by prostate cancer. Death by any cancer was significantly affected by statins with a HR of 0.47, 95% CI: 0.32-0.65 (p < 0.0001). Death by all causes was also affected significantly by statins with a HR of 0.64, 95% CI: 0.53-0.78 (p < 0.0001). Length of statin use, shorter versus longer than 4 years, showed an inverse association with our primary end point with a HR of 0.53, 95% CI: 0.40-0.69 (p < 0.0001). Dose level of statin, fourth level vs 1, 2, and 3, also showed an inverse association with our primary end point with a HR of 0.73, 95% CI: 0.57-0.94 (p = 0.014). Lastly, statin exposure significantly increased progression-free survival with a HR of 0.71, 95% CI: 0.53-0.95 (p < 0.021). Conclusions: It is clear that concomitant statin use increases overall survival in patients with prostate cancer, potentially even having anti-cancer protective effects against mortality. Longer duration of statin use and higher dose levels of statins increase length of overall survival in patients with prostate cancer. As mortality is often not due to prostate cancer, more interestingly, statin exposure is also shown to increase progression-free survival.

scholarly journals Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

2016 ◽  
Vol 34 (21) ◽  
pp. 2478-2483 ◽  
Author(s):  
Darren R. Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Kristina Lim ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Intermediate Risk ◽  
First Line ◽  
Free Survival ◽  
Poor Risk ◽  
End Point

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

Association Between Second Progression-free Survival (PFS2) and Overall Survival in Metastatic Castration-resistant Prostate Cancer

2020 ◽  
Vol 77 (6) ◽  
pp. 763-766 ◽  
Author(s):  
David Lorente ◽  
Elena Castro ◽  
Rebeca Lozano ◽  
Javier Puente ◽  
Nuria Romero-Laorden ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant

scholarly journals Event-Free Survival, a Prostate-Specific Antigen–Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation

2020 ◽  
Vol 38 (26) ◽  
pp. 3032-3041 ◽  
Author(s):  
Wanling Xie ◽  
Meredith M. Regan ◽  
Marc Buyse ◽  
Susan Halabi ◽  
Philip W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Event Free Survival ◽  
Free Survival ◽  
Patient Level ◽  
End Point

PURPOSE Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)–based composite end point, may further expedite trial completion. METHODS EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate–ICECaP–database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ≥ 0.7. RESULTS Data for 10,350 patients were analyzed from 15 radiation therapy–based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall’s tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. CONCLUSION EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy–based trials.

Clinical effectiveness of bevacizumab in patients with recurrent brain tumours: A population-based evaluation

2016 ◽  
Vol 24 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Mário L de Lemos ◽  
Adeline Markarian ◽  
Esther Chan ◽  
Kimberly Schaff ◽  
Susan Walisser
Keyword(s):  
Overall Survival ◽  
Disease Progression ◽  
Brain Tumour ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
The United States ◽  
Free Survival ◽  
Recurrent Brain Tumour

Background Bevacizumab is an antiangiogenic agent active in patients with recurrent malignant gliomas. However, evidence for its clinical efficacy is relatively limited so that bevacizumab is approved for this indication in Canada and the United States, but not in the European Union. We reviewed the effectiveness of bevacizumab in patients with recurrent brain tumour using a large population database. Methods This was a retrospective, multicentre, study conducted at the BC Cancer Agency, a public cancer care organisation for the residents of the Canadian province of British Columbia. Cases were identified from the provincial registry and drug database. Patients were eligible if they were treated with bevacizumab with or without lomustine or etoposide for recurrent brain tumour between April 2011 and March 2014. The primary end points were progression-free survival. Secondary endpoints were overall survival and objective response rate. Results A total of 160 patients were included, with a median age of 55 years. The most common diagnosis was glioblastoma multiforme (70.6%), followed by oligodendroglioma (10.6%). Half of the patients had prior metronomic dosing of temozolomide. The median duration of therapy was 3 months. The median progression-free survival was 4.0 months and the 6-month progression-free survival was 29.4%. The median overall survival was 7 months and the 9-month and 12-month overall survival was 28.1% and 20.6%, respectively. The objective response rate was 23.1%. The most common documented reason for bevacizumab discontinuation was disease progression (66.9%), followed by toxicity (6.9%). Conclusions Bevacizumab therapy seems to be effective in delaying disease progression in patients with recurrent brain tumour, but with limited benefits on the overall survival, when used outside the clinical trial setting.

Association of calcium channel blocker use with prostate cancer aggressiveness, progression-free survival, and overall survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15204-e15204
Author(s):  
Michael Adam Poch ◽  
Diana Mehedint ◽  
Alexandra Curtis ◽  
Kristopher Attwood ◽  
Gregory E. Wilding ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radical Prostatectomy ◽  
Calcium Channel ◽  
Cox Regression ◽  
Medication Use ◽  
Progression Free Survival ◽  
Channel Blockers ◽  
Free Survival ◽  
Cancer Aggressiveness

e15204 Background: Epidemiological studies indicate that the use of calcium channel blockers (CCB) is inversely related to prostate cancer (PCa) incidence. The goal of this study was to examine the association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) or outcome after RP. Methods: Information on medication use, PCa aggressiveness and outcome after RP was retrieved from a prospective database that contains clinical and follow-up (FU) data for all men that have undergone RP at the Department of Urology at Roswell Park Cancer Institute since 1992. The database was queried for anti-hypertensive medication use at the time of diagnosis for all patients with ≥ 1 year FU. Prostate cancer aggressiveness (risk status) and recurrence were defined using NCCN guideline definitions. Cox regression models were performed to compare the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Chi-Square test was used to assess the relationship between CCB use and PCa aggressiveness. Results: 875 men were included in the study. At diagnosis, mean age was 60 (SD ± 7) years and mean serum PSA value was 7.4 (SD ±7.4) ng/ml. 48%, 37%, and 15% of patients had low risk, intermediate risk, or high risk PCa, respectively. 104 (12%) had a history of CCB use. CCB users and non-users were similar by PSA at diagnosis (p=0.97) and tumor aggressiveness (p=0.88). Patients taking CCB were more likely to be older (p=0.023), have a higher BMI (p=0.006) and use additional anti-hypertensive medications (p<0.01). Margin status after radical prostatectomy was similar (p=0.30) between the two groups. Median FU was 42 months. PFS (p=0.82, HR 95% CI: 0.63-1.44) and OS (p=0.72, HR 95% CI: 0.42-3.52) did not differ between the 2 groups. Adjusting for age and PCa aggressiveness did not alter the results observed for PFS (p=0.44, HR 95% CI: 0.62–1.41) and OS (p=0.50, HR 95% CI: 0.04-3.48). PCa aggressiveness was associated with PFS (p=0.001) in the multivariate model. Conclusions: CCB use does not affect PCa aggressiveness at time of diagnosis or improve PFS or OS.

Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Genetic Constitution ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
The Impact

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.

scholarly journals Real-World Outcome of Platinum-Based Chemotherapy in Advanced Breast Cancer (ABC): A Retrospective Study from a Tertiary Cancer Center in India

2021 ◽  
Author(s):  
Indhuja Muthiah Vaikundaraja ◽  
Manikandan Dhanushkodi ◽  
Venkatraman Radhakrishnan ◽  
Jayachandran Perumal Kalaiarasi ◽  
Nikita Mehra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Median Number ◽  
Cancer Center ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Tertiary Cancer Center

Abstract Introduction There is a paucity of data on platinum-based chemotherapy in advanced breast cancer (ABC) from developing countries like India. Objectives The objectives were to analyze the efficacy and safety of platinum-based chemotherapy in patients with ABC. Materials and Methods This was a retrospective study of 35 patients with ABC who were treated with platinum-based chemotherapy (gemcitabine and carboplatin, [GC]) in a tertiary cancer center in India from August 2015 to November 2019. The inclusion criteria were patients with ABC, who had received palliative chemotherapy with GC. The exclusion criteria were patients who had received less than two cycles of GC and patients who received platinum-based chemotherapy for neuroendocrine carcinoma of the breast. Results The median age was 45 years (range: 28–68 years). All patients were female (97%) except one male (3%). The histology was ductal carcinoma (77%), mixed (17%), and others (6%). Out of the 12 patients tested for breast cancer (BRCA) gene mutation, six patients had a BRCA mutation. Patients with metastatic and locally progressive disease were 91 and 9%, respectively. The median number of prior lines of systemic therapy for metastatic disease was 1 (range: 0–5). The median number of sites of metastasis was 2 (range: 0–5). Patients with visceral crises were 23%. The median number of cycles of GC chemotherapy received was 6 (range: 2–6). A dose reduction in chemotherapy was done in 74%. The responses among 34 evaluable patients were complete response (11%), partial response (24%), stable disease (41%), and progressive disease (24%). Grade 3 or more hematological and nonhematological toxicities were observed in 69 and 9%, respectively. The median progression-free survival and overall survival were 6 and 8 months, respectively. The 1-year progression-free survival and overall survival were 19 and 34%, respectively. Multivariate analysis showed that patients who had received more than 3 cycles had a better outcome. Conclusion GC was an active and well-tolerated regimen in ABC regardless of the receptor status. Further prospective randomized studies are warranted to assess the optimal regimen in patients with triple-negative breast cancer.

scholarly journals Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer

2017 ◽  
Vol 35 (27) ◽  
pp. 3097-3104 ◽  
Author(s):  
Wanling Xie ◽  
Meredith M. Regan ◽  
Marc Buyse ◽  
Susan Halabi ◽  
Philip W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Treatment Effects ◽  
Significant Risk ◽  
Localized Prostate Cancer ◽  
Free Survival ◽  
Risk Of Death ◽  
End Point ◽  
Kendall’S Τ

Purpose Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage meta-analytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS. Results Trials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall’s τ correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R2 was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effects—measured by log hazard ratios—for the surrogates and OS were well correlated ( R2, 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS). Conclusion MFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.

HSD3B1 and resistance to androgen deprivation therapy in prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 156-156 ◽  
Author(s):  
Jason W.D. Hearn ◽  
Ghada AbuAli ◽  
Cristina Magi-Galluzzi ◽  
Chandana A. Reddy ◽  
Kai-Hsiung Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Distant Metastasis ◽  
Progression Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Homozygous Variant ◽  
Distant Metastasis Free Survival ◽  
Variant Alleles

156 Background: The somatic mutation HSD3B1(1245A>C) has been mechanistically linked to castration-resistant prostate cancer by encoding a mutant enzyme that augments intratumoral dihydrotestosterone synthesis. Given the HSD3B1(1245C) allele is also frequently found in the germline, we hypothesized men inheriting this variant allele would exhibit resistance to androgen deprivation therapy (ADT), as manifested by worse clinical outcomes. Methods: We used a prospectively maintained prostate cancer registry to identify men treated with ADT for biochemical failure in the post-prostatectomy setting who were without evidence of metastatic disease at the time of ADT initiation. We analyzed progression-free survival, distant metastasis-free survival, and overall survival according to HSD3B1 genotype using Kaplan-Meier methods. Cox proportional hazards regression was performed to evaluate potential gene-dosage effects, with homozygous wild-type men serving as the reference group. Demographic and treatment characteristics were compared across genotypes to assess for possible confounders using Fisher’s exact test and Kruskal-Wallis analysis of variance. Results: Of 118 men genotyped, 37% were homozygous wild-type, 53% were heterozygous, and 10% were homozygous variant. Demographic and treatment characteristics did not differ across groups. Median progression-free survival diminished as a function of the number of variant alleles inherited (6.6 years in homozygous wild-type men, 4.1 years in heterozygotes, and 2.5 years in homozygous variant men; P=0.01). Median distant metastasis-free survival likewise decreased according to the number of variant alleles inherited (9.1 years in homozygous wild-type men, 6.8 years in heterozygotes, and 3.6 years in homozygous variant men; P=0.01). Finally, overall survival also diminished with the number of variant alleles inherited (5-year and 10-year overall survival: 82% and 55% in homozygous wild-type men, 74% and 35% in heterozygotes, and 58% and 0% in homozygous variant men; P=0.006). Conclusions: Inheritance of the variant HSD3B1(1245C) allele that enhances dihydrotestosterone synthesis may predict resistance to ADT for prostate cancer. These findings require validation.

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