M.A.S. Jewett

Impact of 5α-reductase inhibitors on men followed by active surveillance for prostate cancer.

BACKGROUND In two large randomized controlled trials, 5α-reductase inhibitors (5-ARIs) were shown to prevent prostate cancer. No prior work had shown the effect of 5-ARIs on those already diagnosed with low-risk prostate cancer. OBJECTIVE Our aim was to determine the effect of 5-ARIs on pathologic progression in men on active surveillance. DESIGN, SETTING, AND PARTICIPANTS We conducted a single-institution retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on active surveillance for prostate cancer. MEASUREMENTS Pathologic progression was evaluated and defined as Gleason score >6, maximum core involvement >50%, or more than three cores positive on a follow-up prostate biopsy. Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression. RESULTS AND LIMITATIONS A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 mo (interquartile range: 23.6-59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5-ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%; p=0.004) and were less likely to abandon active surveillance (20% vs 37.6%; p=0.006). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (hazard ratio: 2.91; 95% confidence interval, 1.5-5.6). The main study limitation was the retrospective design and variable duration of 5-ARI therapy. CONCLUSIONS The 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance.

De FGFR3-mutatie identificeert patiënten met een relatief gunstige prognose na radicale cystectomie voor blaascarcinoom

Introductie De selectie van patiënten met een laagrisicoprostaatcarcinoom (PCa) voor active surveillance (AS) is gebaseerd op klinisch stadium, PSA en TRUS-geleide biopsiecriteria. Grootste beperking van een dergelijke benadering is de potentiële onderschatting van de werkelijke gecombineerde gleasonscore en het pathologisch stadium. Doel van onze serie is te evalueren in hoeverre de pathologie bij radicale prostatectomie (RP) bij kandidaten voor AS overeenkomt met de preoperatieve klinische en pathologische stadiëring.

SU‐E‐J‐95: Towards Optimum Boundary Conditions for Biomechanical Model Based Deformable Registration Using Intensity Based Image Matching for Prostate Correlative Pathology

PURPOSE Deformable registration of histology to MRI is an essential tool to validate in vivo prostate cancer imaging. However, direct registration of histology to in vivo MR is prone to error due to geometric differences between the tissue sections and the in vivo imaging planes. To increase the accuracy of registration, an ex vivo high resolution MRI is acquired to compensate for the direct registration difficulties. A novel intensity-based deformable registration algorithm based on local variation in image intensities is proposed to register the histology to ex vivo MRI of prostatectomy specimens. METHODS Four sets of ex vivo MR and whole mount pathology images from four patients were used to investigate and validate the technique. In addition, 9 synthetically deformed ex vivo MR images were used. The standard deviation in local windows within the images was calculated to generate intermediate images based on both MR and histology. The intermediate images were registered using the Drop package (Munich, Germany). To further increase the accuracy, a final refinement of the registration was performed using Drop with a finer B-spline rid. The registration parameters were tuned to achieve a visually acceptable registration. Magnitude of Differences (MOD) and Angular Error (AE) were used to validate the synthetic data, and the Target Registration Error (TRE) of manually indicated landmarks was used for the clinical data. RESULTS MOD of 0.6mm and AE of 8.3 degrees showed the efficacy of using intermediate images, compared to 0.8mm and 10.0 degrees achieved with Drop without the intermediate images. The average mean±std TRE among the four patients was 1.0±0.6 mm using the proposed method compared to 1.6±1.1 mm using Elastix (Utrecht, The Netherlands). CONCLUSIONS An intensity-based deformable registration algorithm which uses intermediate images was evaluated on prostatectomy specimens and synthetically deformed clinical data, indicating improvement in overall accuracy and robustness. OICR, Terry Fox Ultrasound for Cancer Therapy. Dr. Brock is a Cancer Care Ontario Research Chair in Cancer Imaging and has financial interest in deformable registration technology through the licensing of Morfeus to RaySearch Laboratories.

1092 5-alpha reductase inhibitors diminish the rate of progression in men with low risk prostate cancer on active surveillance

INTRODUCTION AND OBJECTIVES: 5-alpha reductase inhibitors (5ARIs) have been shown to prevent prostate cancer in two large randomized controlled trials. No prior work has shown the effect of 5ARIs on those already diagnosed with low risk prostate cancer. Our goal was to determine the effect of 5ARIs on pathologic progression in men on active surveillance for prostate cancer. METHODS: This was a single institution retrospective cohort study comparing men taking a 5ARI versus no 5ARI while on active surveillance for prostate cancer. All men had at least two biopsies. Inclusion criteria for active surveillance were PSA 10 ng/ml, clinical stage T1c/T2a, Gleason score 6, and 3 cores positive with no more than 50% of a core involved at initial diagnostic biopsy. Pathologic progression was evaluated and defined as Gleason score 6, or maximum core involvement 50% or 3 cores positive on a follow-up prostate biopsy. Univariate, multivariate and Kaplan-Meir analyses were conducted. RESULTS: A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 months (IQR 23.6– 59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%, p 0.004) and were less likely to abandon active surveillance (20% vs 37.6%, p 0.006). The median time to progression was longer in the 5ARI group (42.5 months) compared to the non-5ARI group (31.5 months; p 0.026). On multivariate analysis, lack of 5ARI use was most strongly associated with pathologic progression (OR 2.98, 95% CI 1.5–5.9) followed by age and baseline maximum percentage involvement of any biopsy core. CONCLUSIONS: 5ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance.

299 ANDROGEN RECEPTOR (AR) AND BLADDER CANCER: A LARGE BI-INSTITUTIONAL STUDY ON 473 PATIENTS

S143 only in the Triton-insoluble fraction. Under non-reducing conditions, PRDX 1 and 6 were found as bands of high molecular weight (>170 kDa) in spermatozoa incubated with 0.35-5 mM H2O2 (strong oxidative stress). PRDX 6 became a strong single band due to a mild oxidative stress (0.05 mM H2O2, a condition that promotes sperm capacitation). H2O2 (0.35-5 mM) caused a decrease of the signal for PRDX 4 and 5 compared to non-treated cells. Conclusion: PRDXs are present in human spermatozoa and differentially modified by oxidative stress. These results suggest a role of PRDXs as antioxidants and as potential modulators of H2O2 action in human spermatozoa.