Active surveillance of very-low-risk prostate cancer in the setting of active treatment of benign prostatic hyperplasia with 5α-reductase inhibitors.

OBJECTIVE: To review the efficacy of treating benign prostatic hyperplasia and very-low-risk prostate cancer (PCa) in patients receiving active surveillance and 5α-reductase inhibitor (5-ARI; finasteride or dutasteride) treatment. MATERIALS AND METHODS: Eighty-two men with very-low-risk PCa (clinical stage T1c, Gleason score ≤ 6, <3 biopsy cores positive with ≤ 50% involvement, and prostate-specific antigen density ≤ 0.15 ng/mL/g) and benign prostatic hyperplasia (≥ 30 cm(3)) received active surveillance and were treated with a 5-ARI. RESULTS: All 82 men completed 1 year of 5-ARI therapy (n = 79) or underwent early biopsy for cause (n = 3). Restaging biopsies were performed for 76 men (22 underwent a second restaging biopsy and 1 a third restaging biopsy), 4 patients were awaiting biopsy, and 2 were lost to follow-up before the first restaging biopsy. At the first restaging biopsy, of the 76 men, 41 (54%) had no PCa, 16 (21%) continued to have very-low-risk PCa, 15 (20%) had progressed to low-risk PCa (>2 cores positive and Gleason score ≤ 6), and 4 (5%) had progressed to intermediate-risk PCa (Gleason score 7). Of the 76 biopsies, 20 were performed early for cause, with 11 (55%) showing PCa progression. Of the 82 patients, 22 (27%) underwent treatment of PCa. CONCLUSION: Active surveillance of very-low-risk PCa in the setting of 5-ARI therapy for benign prostatic hyperplasia appears to be a safe therapeutic option, because most (57 of 82; 70%) patients maintained very-low-risk PCa or had negative follow-up biopsies during a 3-year follow-up period. Complementary to the Prostate Cancer Prevention Trial, our results indicate that 5-ARI therapy increases prostate-specific antigen sensitivity and can aid the clinician in appropriately targeting biopsies.

Two-step transurethral surgery of the prostate and permanent implant brachytherapy for patients with lower urinary tract symptoms and low- to intermediate-risk prostate cancer.

PURPOSE: Prostate brachytherapy is an increasingly used treatment option for low- to intermediate-risk prostate cancer (PCa). However, patients with preexisting lower urinary tract symptoms (LUTS) and PCa, who would otherwise be good brachytherapy candidates, are often contraindicated because of the risk of postoperative urinary morbidity. We report our clinical experience with limited transurethral resection of the prostate (LTURP) and/or transurethral incision of the prostate (TUIP) months before brachytherapy to treat patients with LUTS and low- to intermediate-risk PCa. METHODS AND MATERIALS: Of 258 men undergoing prostate brachytherapy at our institution between 1998 and 2011, 42 were treated with planned LTURP and/or TUIP well before (mean, 5.7 months) seed implantation. Transurethral surgery was considered before brachytherapy for patients who at presentation required α-blocker therapy for LUTS, had an International Prostate Symptom Score greater than 14 off α-blockers, or had an elevated postvoid residual (>100 mL). Patients only proceeded to brachytherapy once LUTS resolved. RESULTS: All 42 patients in our series underwent TUIP (25), LTURP (7), or TUIP/LTURP (10) with mean 5.7 months before prostate brachytherapy for low- or intermediate-risk PCa. Mean International Prostate Symptom Score, peak flow rate, and postvoid residual significantly improved after transurethral surgery, and improvement persisted at the latest followup. No patient developed retention, urethral necrosis, or urinary incontinence after transurethral surgery or brachytherapy (median followup, 39 months and range, 1-121). CONCLUSIONS: Planned LTURP and/or TUIP more than 4 months before brachytherapy is a safe and effective treatment strategy for men with LUTS and low- to intermediate-risk PCa.

A novel predicted bromodomain-related protein affects coordination between meiosis and spermiogenesis in Drosophila and is required for male meiotic cytokinesis.

Temporal coordination of meiosis with spermatid morphogenesis is crucial for successful generation of mature sperm cells. We identified a recessive male sterile Drosophila melanogaster mutant, mitoshell, in which events of spermatid morphogenesis are initiated too early, before meiotic onset. Premature mitochondrial aggregation and fusion lead to an aberrant mitochondrial shell around premeiotic nuclei. Despite successful meiotic karyokinesis, improper mitochondrial localization in mitoshell testes is associated with defective astral central spindles and a lack of contractile rings, leading to meiotic cytokinesis failure. We mapped and cloned the mitoshell gene and found that it encodes a novel protein with a bromodomain-related region. It is conserved in some insect lineages. Bromodomains typically bind to histone acetyl-lysine residues and therefore are often associated with chromatin. The Mitoshell bromodomain-related region is predicted to have an alpha helical structure similar to that of bromodomains, but not all the crucial residues in the ligand-binding loops are conserved. We speculate that Mitoshell may participate in transcriptional regulation of spermatogenesis-specific genes, though perhaps with different ligand specificity compared to traditional bromodomains.