Transurethral Resection of the Prostate Biopsy of Suspected Anterior Prostate Cancers Identified by Multiparametric Magnetic Resonance Imaging: A Pilot Study of a Novel Technique.

OBJECTIVE: To describe a novel biopsy technique that involves performing a cognitively directed transurethral resection of the prostate (TURP) to diagnose suspected anterior prostate cancers (APCs) detected by multiparametric magnetic resonance imaging (mpMRI) in patients with prior negative transrectal ultrasound (TRUS)-guided biopsies. METHODS: This is a prospective study in which participants aged 50-75 were offered inclusion if they had an elevated prostate-specific antigen level, a lesion suspicious for APC on mpMRI, and at least one prior negative TRUS-guided prostate biopsy. Prostatic mpMRI was acquired with a 3-Tesla machine without endorectal coil. Preoperative review of the mpMRI images was used to target the suspected APC on TURP biopsy. The primary outcome was the detection rate of clinically significant prostate cancer, defined as the presence of any Gleason pattern ≥ 4 in the specimen. Secondary outcomes included biopsy-related complications including 30-day readmissions. RESULTS: A total of 16 consecutive participants were enrolled. Median age was 64 years, median prostate-specific antigen was 12.4 ng/mL, and participants had a median of 2 prior negative TRUS-guided biopsies. Thirteen (81.3%) participants had clinically significant APCs detected by TURP biopsy. One participant was readmitted within 30-days postprocedure for continuous bladder irrigation. Seven participants (43.8%) underwent radical prostatectomy that confirmed clinically significant disease in all 7 participants. CONCLUSION: Among participants with anterior prostate lesions on mpMRI and prior negative TRUS-guided biopsy, TURP biopsy does detect some clinically significant cancers. This study serves as a proof of concept and further comparative trials are needed prior to widespread adoption.

Current management of advanced and castration resistant prostate cancer.

INTRODUCTION: Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium 223 have all been approved since 2010 to treat metastatic castration resistant prostate cancer (CRPC). New imaging techniques to detect advanced disease such as F-18 PET, 11 C-choline PET and other modalities are becoming available. The concepts of "bone health" and the management of side effects related to androgen deprivation therapy are also gaining attention as men are being treated with longer courses of androgen deprivation. Understanding the theory behind these new agents and management approaches while focusing on the practical clinical considerations are essential to improve outcomes in advanced prostate cancer. MATERIALS AND METHODS: A review of the current state of the art in the management of advanced and castration resistant prostate cancer presented in this Canadian Journal of Urology International supplement was performed. Key findings are summarized and presented along with critical updates based on recent publications and meeting presentations. RESULTS: Key concepts identified in the management of advanced prostate cancer included the new understanding of prostate cancer based on translational discoveries, applications of various hormonally based strategies in advanced disease including traditional and recently approved agents. The use of new imaging modalities to identify metastatic disease, immunotherapy approaches and discussions of sequencing and which new agents are likely to be available in the future in the management of CRPC were identified. Bone targeted strategies are also addressed in the setting of androgen deprivation and metastatic disease. CONCLUSIONS: The management of men with advanced prostate cancer has become more multidisciplinary as treatment options have expanded. As the use of these agents and new strategies expand, urologists, medical oncologists and radiation oncologists must all become familiar with this rapidly changing field in order to maximize the outcome of patients with advanced and castration resistant prostate cancer.

Inter-related in vitro effects of androgens, fatty acids and oxidative stress in prostate cancer: a mechanistic model supporting prevention strategies.

Oxidation of mitochondrial fatty acids (FA) results in the generation of reactive oxygen species (ROS) which have been postulated to play a key role in the initiation and progression of prostate cancer (PC). We previously reported that androgens increase FA uptake into PC cells. We thus examined if androgens that are known to induce ROS generation regulate FA oxidation in PC cells. The effects of the androgen-depleted medium, R1881 (synthetic androgen) and/or androgen receptor blocker, bicalutamide were examined in the human androgen-responsive but not dependent 22rv1 cells. R1881 supplementation significantly increased mitochondrial FA oxidation ((14)C-radiolabeled FA degradation studies), resulting in increased ROS production. Androgens increased the mRNA levels of carnitine palmitoyltransferase (CPT1), the rate limiting enzyme in the process of mitochondrial FA oxidation. Treatment with R1881 and bicalutamide inhibited these androgen regulated effects. Inhibition of mitochondrial ROS generation by two different inhibitors, rotenone and thenoyltrifluoroacetone, eliminated the androgen-induced ROS generation, to the same level as in cells deprived of androgens or treated with R1881 and bicalutamide. Taken together, androgens increase the mitochondrial oxidation of FA, leading to increased production of ROS that is associated with prostate cell proliferation and mutagenesis. These results therefore support the rationale for PC prevention using 5-alpha reductase inhibitors, dietary restrictions or anti-oxidants, each of which has different inhibitory but complementary effects.