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Contains fulltext : 220508.pdf (Publisher’s version ) (Closed access) PURPOSE: Available published studies evaluating the association between nerve sparing robot-assisted radical prostatectomy and risk of ipsilateral positive surgical margins were subject to selection bias. In this study we overcome these limitations by using multivariable regression analysis. MATERIALS AND METHODS: Patients undergoing robot-assisted radical prostatectomy for prostate cancer at 4 institutions from 2013 to 2018 were included in the study. A multilevel logistic random intercept model, including covariates on patient level and side specific factors on prostate lobe level, was used to evaluate the association between nerve sparing and risk of ipsilateral positive margins. RESULTS: A total of 5,148 prostate lobes derived from 2,574 patients who underwent robot-assisted radical prostatectomy were analyzed. Multivariable analysis showed nerve sparing was an independent predictor for ipsilateral positive margins (OR 1.42, 95% CI 1.14-1.82). Other significant predictors for positive margins were prostate specific antigen density (OR 3.64, 95% CI 2.36-5.90) and side specific covariates including highest preoperative ISUP (International Society of Urological Pathology) biopsy grade (OR 1.58, 95% CI 1.13-2.53; OR 1.62, 95% CI 1.13-2.69; OR 2.11, 95% CI 1.39-3.59 and OR 4.43, 95% CI 3.17-10.12 for ISUP grade 2, 3, 4 and 5, respectively), presence of extraprostatic extension on magnetic resonance imaging (OR 1.42, 95% CI 1.03-1.91) and percentage of positive cores on systematic biopsy (OR 3.82, 95% CI 2.50-5.86). CONCLUSIONS: Nerve sparing was associated with an increased risk of ipsilateral positive surgical margins. The increased risk of positive margins should be considered when counseling patients who opt for nerve sparing robot-assisted radical prostatectomy.

Contains fulltext : 220692.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext PURPOSE: Dihydrotestosterone is the main active androgen in the prostate and it has a role in prostate cancer progression. After androgen deprivation therapy androgen receptor signaling is still active in tumor cells. Persistent intratumor steroidogenesis and androgen receptor changes are responsible for this continued activity, which influences the efficacy of prostate cancer treatment. We hypothesized that combining a 5alpha-reductase inhibitor and an antiandrogen would block intratumor androgen synthesis and androgen receptor protein activity. Thus, it would act synergistically to reduce tumor cell proliferation. MATERIALS AND METHODS: The expression level of 5alpha-reductase and androgen receptor in endocrine therapy naive prostate cancer and castration resistant prostate cancer tissues, and cell line models was determined by microarray and quantitative polymerase chain reaction analysis. Intracellular androgen was measured with radioimmunoassay. Tumor cell proliferation was determined using coloric MTT assay. The synergistic effects of combination treatments on tumor cell proliferation were calculated using the Chou-Talalay equation. RESULTS: In all prostate cancer cases 5alpha-reductase-1 and 3 were up-regulated. Androgen receptor was up-regulated in metastatic prostate cancer and castration resistant prostate cancer cases. The 5alpha-reductase inhibitor dutasteride effectively decreased dihydrotestosterone production in prostate cancer and castration resistant prostate cancer cell lines. Furthermore, dutasteride combined with the novel antiandrogen enzalutamide synergistically suppressed endocrine therapy naive prostate cancer and castration resistant prostate cancer cell proliferation. CONCLUSIONS: In this study the combination of a 5alpha-reductase inhibitor and (novel) antiandrogens synergistically inhibited tumor cell proliferation. These findings support clinical studies of combinations of a 5alpha-reductase inhibitor and (novel) antiandrogens as first line treatment of prostate cancer and castration resistant prostate cancer.

Item does not contain fulltext PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. MATERIALS AND METHODS: The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. RESULTS: The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. CONCLUSIONS: The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression.

Contains fulltext : 136616.pdf (Publisher’s version ) (Open Access) PURPOSE: Urinary biomarker tests for diagnosing prostate cancer have gained considerable interest. Urine is a complex mixture that can be subfractionated. We evaluated 2 urinary fractions that contain nucleic acids, ie cell pellets and exosomes. The influence of digital rectal examination before urine collection was also studied and the prostate cancer specific biomarkers PCA3 and TMPRSS2-ERG were assayed. MATERIALS AND METHODS: Urine samples were prospectively obtained before and after digital rectal examination from 30 men scheduled for prostate biopsy. Cell pellet and exosomes were isolated and used for biomarker analysis. Analytical and diagnostic performance was tested using the Student t-test and ROC curves. RESULTS: Unlike the exosome fraction, urinary sediment gene expression analysis was compromised by amorphous precipitation in 10% of all specimens. Digital rectal examination resulted in increased mRNA levels in each fraction. This was particularly relevant for the exosomal fraction since after digital rectal examination the number of samples decreased in which cancer specific markers were below the analytical detection limit. Biomarker diagnostic performance was comparable to that in large clinical studies. In exosomes the biomarkers had to be normalized for prostate specific antigen mRNA while cell pellet absolute PCA3 levels had diagnostic value. CONCLUSIONS: Exosomes have characteristics that enable them to serve as a stable substrate for biomarker analysis. Thus, digital rectal examination enhances the analytical performance of biomarker analysis in exosomes and cell pellets. The diagnostic performance of biomarkers in exosomes differs from that of cell pellets. Clinical usefulness must be prospectively assessed in larger clinical cohorts.

Item does not contain fulltext PURPOSE: Nonmuscle invasive bladder cancer is characterized by a high recurrence rate. New adjuvant treatments are needed to decrease this high number of recurrences. We present the results of more than 10 years of experience with chemohyperthermia in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Using standardized medical record forms we prospectively collected patient and tumor characteristics of patients treated with chemohyperthermia between 2002 and 2013. Median followup was 75.6 months. Recurrence-free survival was the primary objective. The secondary objective was to observe recurrence-free survival differences in 1) the epirubicin group vs the mitomycin group and 2) the highly recurrent (greater than 2 recurrences in 24 months) nonmuscle invasive bladder cancer group vs the other groups. RESULTS: A total of 160 patients with nonmuscle invasive bladder cancer were included in study, including 20 (13%) treated with epirubicin and 129 (81%) previously treated with bacillus Calmette-Guerin. One and 2-year recurrence-free survival was 60% and 47%, respectively. Muscle invasive progression was seen in 4% of cases. Two-year recurrence-free survival in the epirubicin and mitomycin groups was 55% and 46%, respectively (p = 0.30). The highly recurrent nonmuscle invasive bladder cancer group had significant decreased recurrence-free survival compared to other groups (p