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Background The treatment of non-localized prostate cancer involves androgen deprivation (AD) therapy which results in tumor regression. Apoptosis has been implicated in the tumor response to AD, but constitutes a small fraction of the total tumor at any time. Cellular senescence is a response to sub-lethal stress in which cells are persistently growth arrested and develop distinct morphological and biochemical characteristics. The occurrence of senescence in prostate tumor tissue after AD therapy has not previously been investigated. Methods Phenotypic and molecular characteristics of senescence were examined in models of androgen-sensitive prostate cancer after AD and compared with androgen-intact controls. Results In vitro in LNCaP cells, AD induced elevated senescence-associated β-galactosidase (SA-β-gal) staining, decreased proliferation, and increased flow cytometric side scatter while minimally affecting cell viability. The increased expression of the senescence-related proteins Glb1, the cyclin-dependent kinase inhibitor p27Kip1 and chromatin-regulating heterochromatin protein 1γ (HP1γ) were detected in LNCaP cells after AD in vitro by immunoblot and immunofluorescence microscopy. In mice bearing LuCaP xenograft tumors in vivo, surgical castration similarly increased SA-β-gal staining, increased expression of p27Kip1 and HP1γ, and decreased expression of the proliferation marker KI-67, with minimal induction of apoptosis identified by detection of cleaved caspase 3 and TUNEL. Immunohistochemical analysis of human prostate tumors removed after AD shows similar induction of Glb1, HP1γ and decreased KI-67. Conclusions We conclude that AD induces characteristics consistent with cellular senescence in androgen-sensitive prostate cancer cells. This finding may explain incomplete tumor regression in response to AD.

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Introduction and Objective Active surveillance (AS) is an option for the management of favorable risk prostate cancer (CaP) in the PSA era. Published studies have reported variable inclusion criteria for cohort selection. Accurate assessment of individual patient risk in AS is dependent not only upon rigorous selection criteria, but also reliability of diagnosis at tissue biopsy. To date, the impact of immediate transrectal ultrasound (TRUS) rebiopsy in confirming candidates for AS has been incompletely defined. Methods From a total of over 567 men, 67 met criteria for AS (Gleason <7, PSA <10, PSAD <0.15, <3 cores with <50% involvement of any 1 core). Fifty-two men agreed to a 12-core TRUS rebiopsy within 6 months of first diagnosis performed in clinic. Statistical analysis was performed using Wilcoxon signed rank test and logistic regression to determine predictors of rebiopsy characteristics, histopathologic outcomes, and impact on treatment choice. Results Mean cohort age was 63.9 years (range 56–72 years), PSA 5.9 ng/ml (4.1–10), and PSA density 0.12 ng/ml/cc at initial biopsy. Tumor involved 1.1 cores and 3.2% (range 1%–5%) of the total tissue. Average time to rebiopsy was 2.7 months. Notably, 29 of 52 men (56%) demonstrated no evidence of CaP on repeat biopsy; 14 of 23 men with a positive repeat biopsy showed either an increase in cancer volume (2.8% mean increase) and 9 (18%) were upgraded to Gleason pattern 3+4 = 7. Rebiopsy demonstrated 9 (17%) patients exceeded AS criteria. Nine patients chose curative surgical intervention (radical prostatectomy) based on increased cancer volume or grade (4) or an elective desire for treatment (5). All had organ confined disease with negative margins on final pathologic analysis. Statistical review revealed that initial Gleason score, PSA density, and number of positive cores at first biopsy were not predictive of men with higher volume/grade on re-biopsy. Conclusions Immediate TRUS repeat biopsy after diagnosis frequently fails to redemonstrate prostate cancer confirming the favorable-risk nature of disease burden in this group being considered for AS. A subset of patients are upgraded (17%) leading to reconsideration of AS. We conclude this clinic-based approach provides valuable additional information to discriminate appropriate AS candidates.

The introduction of minimally invasive surgery for radical retropubic prostatectomy has increased the incidence of recognition of accessory pudendal arteries. Early identification and preservation of these vessels is paramount for optimal functional outcomes. In this article, we describe our robotic surgical technique for identification and preservation of both lateral and apical accessory pudendal arteries. The illuminated, magnified surgical field, the pneumoperitoneum which minimizes venous bleeding, and the ability to acutely angle the robotic instruments assists in the preservation of these arteries. Although anatomy precludes the preservation of all accessory pudendal arteries, adopting a strategic approach to robotic dissection allows accessory pudendal arteries to be successfully spared in most cases.