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736 Dutasteride for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: Results of phase III randomized open label trial
736
Dutasteride for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: Results of phase III randomized open label trial Eur Urol Suppl 2014;13;e736
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Milonas D.1 , Skulcius G.1 , Auskalnis S. 1 , Kincius M. 1 , Gudinaviciene I.2 , Jievaltas M. 1 1 Lithuanian
Health Science University, Dept. of Urology, Kaunas, Lithuania, 2 Lithuanian Health Science University, Dept. of Pathology,
Kaunas, Lithuania INTRODUCTION & OBJECTIVES: Prostate cancer (PCa) prevention remains an appealing strategy for the reduction of overtreatment and secondary adverse events after radical treatment. We evaluated the efficacy of dutasteride 0.5 mg in PCa prevention among men with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy. MATERIAL & METHODS: Two hundred and twenty one men with firstly detected HGPIN and no PCa on prostate biopsy were randomly assigned to receive dutasteride 0.5 mg or active surveillance in a phase III open label trial. Men underwent ten cores biopsies at 6, 12, 24 and 36 months until cancer detection or end of study. Efficacy analysis was performed in 191 men who underwent at least one on-study biopsy. PCa free survival was evaluated using Kaplan-Meier method. Baseline risk factors were evaluated to determine influence on cancer detection using multivariate logistic regression and Cox regression models. RESULTS: One hundred and six men were randomly involved for active surveillance and eighty five – for treatment with dutasteride. Mean patients age was 65.6 (range 50-79) years, mean PSA 6.5 (0.5-24.2) ng/ml and mean PSA density 0.18 (0.02-0.81) with no difference between groups. The mean prostate volume in treatment group was 45.6 (14.9-110) mL and in surveillance group – 39.6 (13.2-102.3) mL (p=0.028). PCa was detected in 47.2% and 44.7% of men in the surveillance and treatment groups (p=0.734), respectively. There were no differences comparing PCa differentiation between treatment and surveillance groups: Gleason 6 – 79 vs. 76.5%; Gleason 7 – 18.4 vs. 19.5% and Gleason 8-9 – 2.6 vs. 4.0%, respectively. Patients with detected PCa had higher PSA 7.29 vs. 5.76 (p=0.017), PSA density 0.21 vs. 0.15 (p=0.002) and were older 66.8 vs. 64.7 (p=0.04) at baseline comparing to men with no PCa at the end of study. The 4-year PCafree survival rate was 36.7% in the surveillance and 37.2% in the dutasteride groups (log rank p=0.816). Estimated median PCa free survival time was 27.6 (95%CI 14.934-40.326) months for surveillance and 37.0 (95%CI 20.904-53.096) months for dutasteride group. Evaluation of baseline risk factors (multivariate Cox regression analysis) demonstrated that lower PSA density significantly reduce risk of PCa detection (p <0.015, HR 8.58, 95% CI 1,506-48.931). Independently on treatment or no treatment for 27.53%, 16.9%, 14.5% and 8.6% of man PCa was detected after 1st, 2nd , 3rd and 4th repeat ten cores biopsy, respectively. CONCLUSIONS: Dutasteride 0.5 mg did not lower the PCa detection rate in men with HGPIN. Men with HGPIN have a high likelihood of eventual PCa diagnosis and require surveillance by periodic prostate biopsy.
Dutasteride for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: Results of phase III randomized open label trial Eur Urol Suppl 2014;13;e736
Print! Print!
Milonas D.1 , Skulcius G.1 , Auskalnis S. 1 , Kincius M. 1 , Gudinaviciene I.2 , Jievaltas M. 1 1 Lithuanian
Health Science University, Dept. of Urology, Kaunas, Lithuania, 2 Lithuanian Health Science University, Dept. of Pathology,
Kaunas, Lithuania INTRODUCTION & OBJECTIVES: Prostate cancer (PCa) prevention remains an appealing strategy for the reduction of overtreatment and secondary adverse events after radical treatment. We evaluated the efficacy of dutasteride 0.5 mg in PCa prevention among men with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy. MATERIAL & METHODS: Two hundred and twenty one men with firstly detected HGPIN and no PCa on prostate biopsy were randomly assigned to receive dutasteride 0.5 mg or active surveillance in a phase III open label trial. Men underwent ten cores biopsies at 6, 12, 24 and 36 months until cancer detection or end of study. Efficacy analysis was performed in 191 men who underwent at least one on-study biopsy. PCa free survival was evaluated using Kaplan-Meier method. Baseline risk factors were evaluated to determine influence on cancer detection using multivariate logistic regression and Cox regression models. RESULTS: One hundred and six men were randomly involved for active surveillance and eighty five – for treatment with dutasteride. Mean patients age was 65.6 (range 50-79) years, mean PSA 6.5 (0.5-24.2) ng/ml and mean PSA density 0.18 (0.02-0.81) with no difference between groups. The mean prostate volume in treatment group was 45.6 (14.9-110) mL and in surveillance group – 39.6 (13.2-102.3) mL (p=0.028). PCa was detected in 47.2% and 44.7% of men in the surveillance and treatment groups (p=0.734), respectively. There were no differences comparing PCa differentiation between treatment and surveillance groups: Gleason 6 – 79 vs. 76.5%; Gleason 7 – 18.4 vs. 19.5% and Gleason 8-9 – 2.6 vs. 4.0%, respectively. Patients with detected PCa had higher PSA 7.29 vs. 5.76 (p=0.017), PSA density 0.21 vs. 0.15 (p=0.002) and were older 66.8 vs. 64.7 (p=0.04) at baseline comparing to men with no PCa at the end of study. The 4-year PCafree survival rate was 36.7% in the surveillance and 37.2% in the dutasteride groups (log rank p=0.816). Estimated median PCa free survival time was 27.6 (95%CI 14.934-40.326) months for surveillance and 37.0 (95%CI 20.904-53.096) months for dutasteride group. Evaluation of baseline risk factors (multivariate Cox regression analysis) demonstrated that lower PSA density significantly reduce risk of PCa detection (p <0.015, HR 8.58, 95% CI 1,506-48.931). Independently on treatment or no treatment for 27.53%, 16.9%, 14.5% and 8.6% of man PCa was detected after 1st, 2nd , 3rd and 4th repeat ten cores biopsy, respectively. CONCLUSIONS: Dutasteride 0.5 mg did not lower the PCa detection rate in men with HGPIN. Men with HGPIN have a high likelihood of eventual PCa diagnosis and require surveillance by periodic prostate biopsy.