The Detection of Prostate Cancer with Magnetic Resonance Imaging-Targeted Prostate Biopsies is Superior with the Transperineal vs the Transrectal Approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-Institutional Study.

PURPOSE: Our aim was to evaluate whether transperineal (TP) MRI-targeted prostate biopsy (TBx) may improve the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology ≥2, in comparison to transrectal (TR) TBx. MATERIALS AND METHODS: A multicenter retrospective cohort study comprising patients who underwent MRI-guided prostate biopsy was conducted. To address possible benefits of TP-TBx in the detection of prostate cancer (PCa) and csPCa, a cohort of patients undergoing TP-TBx were compared to patients undergoing TR-TBx. Multivariable logistic regression analyses were performed to assess predictors of PCa and csPCa detection. RESULTS: Overall, 1,936 and 3,305 patients who underwent TR-TBx vs TP-TBx at 10 referral centers were enrolled. The rate of PCa and csPCa diagnosed was higher for TP-TBx vs TR-TBx (64.0% vs 50%, p <0.01 and 49% vs 35%, p <0.01). At multivariable analysis adjusted for age, biopsy naïve/repeated biopsy, cT stage, Prostate Imaging-Reporting and Data System®, prostate volume, PSA, and number of biopsy cores targeted, TP-TBx was an independent predictor of PCa (odds ratio [OR] 1.37, 95% CI 1.08-1.72) and csPCa (1.19, 95% CI 1.12-1.50). When considering the approach according to the site of the index lesion, TP-TBx had a significantly higher likelihood than TR-TBx to detect csPCa in the apex (OR 4.81, 95% CI 1.03-6.27), transition/central zone (OR 2.67, 95% CI 1.42-5.00), and anterior zone (OR 5.62, 95% CI 1.74-8.13). CONCLUSIONS: The use of TP-TBx allows a better cancer grade definition and PCa risk assessment. This has important implication in the decision-making process and in patient counseling for further therapies.

Predictors of erectile dysfunction after transperineal template prostate biopsy.

PURPOSE: To investigate the incidence and possible contributing factors of erectile dysfunction (ED) after transperineal template prostate biopsy (TTPB). MATERIALS AND METHODS: Males undergoing TTPB were prospectively administered a Sexual Health Inventory for Men (SHIM) questionnaire before biopsy and one month after. SHIM questionnaires were repeated at 3- and 9-months for males not receiving interventional treatment. Sexually inactive males were excluded. Interval change in SHIM categories based upon baseline characteristics were evaluated. Multivariable logistic regression models were used to evaluate predictors of change in SHIM score category. RESULTS: A total of 576 males were included in our sample. Of these, 450 (78%) males underwent their first biopsy. A decline in SHIM category within the immediate 4-weeks post-biopsy was reported by 167 males (31% of total eligible sample). Age was the strongest predictor of decline in SHIM category, the predicted probability of a decline in SHIM at age 50 was 10% (95% confidence interval [CI], 1%-19%), 32% at age 60 (95% CI, 25%-40%) and 36% at age 70 (95% CI, 29%-44%). For new onset ED, the predicted probability of ED within 4-weeks post-TTPB were 6.7% at age 50 (95% CI, 0%-15%), 26% at age 60 (95% CI, 17%-34%) and 31% at age 70 (95% CI, 21%-40%). CONCLUSIONS: Older age at biopsy is an independent predictor of immediate ED after TTPB in sexually active males. This association was observed in the subgroup with no pre-existing ED. These findings provide useful information when counselling males undergoing TTPB.

Patient-derived Models of Abiraterone- and Enzalutamide-resistant Prostate Cancer Reveal Sensitivity to Ribosome-directed Therapy.

BACKGROUND: The intractability of castration-resistant prostate cancer (CRPC) is exacerbated by tumour heterogeneity, including diverse alterations to the androgen receptor (AR) axis and AR-independent phenotypes. The availability of additional models encompassing this heterogeneity would facilitate the identification of more effective therapies for CRPC. OBJECTIVE: To discover therapeutic strategies by exploiting patient-derived models that exemplify the heterogeneity of CRPC. DESIGN, SETTING, AND PARTICIPANTS: Four new patient-derived xenografts (PDXs) were established from independent metastases of two patients and characterised using integrative genomics. A panel of rationally selected drugs was tested using an innovative ex vivo PDX culture system. INTERVENTION: The following drugs were evaluated: AR signalling inhibitors (enzalutamide and galeterone), a PARP inhibitor (talazoparib), a chemotherapeutic (cisplatin), a CDK4/6 inhibitor (ribociclib), bromodomain and extraterminal (BET) protein inhibitors (iBET151 and JQ1), and inhibitors of ribosome biogenesis/function (RNA polymerase I inhibitor CX-5461 and pan-PIM kinase inhibitor CX-6258). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Drug efficacy in ex vivo cultures of PDX tissues was evaluated using immunohistochemistry for Ki67 and cleaved caspase-3 levels. Candidate drugs were also tested for antitumour efficacy in vivo, with tumour volume being the primary endpoint. Two-tailed t tests were used to compare drug and control treatments. RESULTS AND LIMITATIONS: Integrative genomics revealed that the new PDXs exhibited heterogeneous mechanisms of resistance, including known and novel AR mutations, genomic structural rearrangements of the AR gene, and a neuroendocrine-like AR-null phenotype. Despite their heterogeneity, all models were sensitive to the combination of ribosome-targeting agents CX-5461 and CX-6258. CONCLUSIONS: This study demonstrates that ribosome-targeting drugs may be effective against diverse CRPC subtypes including AR-null disease, and highlights the potential of contemporary patient-derived models to prioritise treatment strategies for clinical translation. PATIENT SUMMARY: Diverse types of therapy-resistant prostate cancers are sensitive to a new combination of drugs that inhibit protein synthesis pathways in cancer cells.

Comparison of perioperative, renal and oncologic outcomes in robotic-assisted versus open partial nephrectomy.

BACKGROUND: To compare perioperative, renal and oncological outcomes after robotic-assisted partial nephrectomy (RAPN) versus open partial nephrectomy (OPN) for the treatment of renal tumours. METHODS: All partial nephrectomies performed at a Metropolitan Urology Centre between 2010 and 2016 were analysed. Baseline data was collected for patient demographics, tumour characteristics (tumour size, laterality and polarity, RENAL scores), and perioperative variables (e.g. warm ischaemic time, operation time, estimated blood loss (EBL), length of stay). Tumour characteristics included malignancy, clinical stage, Fuhrman nuclear grade and surgical margin status. Day-1 post-operative serum creatinine, estimated glomerular filtration rate (eGFR) and 6-month eGFR stage were used for assessing renal function. RESULTS: Two hundred patients underwent partial nephrectomy between 2010 and 2016 (n = 200; 55 OPN versus 145 RAPN). Baseline data was similar between groups, except for lower age (P = 0.0001) and higher RENAL scores (P = 0.001) in the RAPN group. RAPN demonstrated significantly lower complication rates (P = 0.015), lesser EBL (P = <0.0001), shorter hospital stays (P = <0.001) and reduced positive tumour resection margins (P = 0.039). There was no significant difference in mean operation time between RAPN and OPN (137.2 (±48.0) OPN versus 146.07 (±35.91) RAPN; P = 0.16). No statistical difference was shown for post-operative eGFR stage between groups at Day-1 and 6-month post-surgery (P = 0.15 and P = 0.861, respectively). CONCLUSION: We present the largest reported Australian series on partial nephrectomy, confirming that a robotic-assisted approach is equivalent to OPN, with reduced complications, EBL, length of hospital stays and fewer positive margins, even when resecting more complex tumours.

Zero hospital admissions for infection after 577 transperineal prostate biopsies using single-dose cephazolin prophylaxis.

PURPOSE: To determine the rate of hospital admissions for infection after transperineal biopsy of prostate (TPB) with single-dose cephazolin prophylaxis using a prospective database. METHOD: Between April 2013 and February 2016, 577 patients undergoing TPB had 2 g of cephazolin given intravenously at induction of anaesthesia. Data collected from these patients included age, PSA, prostate volume, number of cores taken and post-operative complications. RESULTS: No patients were readmitted to hospital with infection post-TPB. Seven patients developed acute urinary retention, and one patient developed clinical prostatitis that was treated with oral antibiotics in the community. CONCLUSION: It is safe to use single-dose cephazolin only as antibiotic prophylaxis prior to TPB, negating the need for quinolones. This study supports Australia's current Therapeutic Guidelines recommendation for TPB prophylaxis and the existing evidence that sepsis post-TPB is a rare complication. Whether any antibiotic prophylaxis is needed at all for TPB is the subject of a future study.

Prioritizing patients for prostatectomy: balancing clinical and psychosocial factors.

BACKGROUND: The aim of this study was to develop a points-based approach to prioritize patients for elective transurethral resection of the prostate and to determine the relative contributions that clinical and psychosocial characteristics should make to a measurement of urgency for surgery. Another objective was to measure the agreement between urologists, other medical practitioners and laypersons in assessing the major determinants of priority. METHODS: A focus group of urologists and epidemiologists developed a standard questionnaire identifying relevant clinical and psychosocial factors in men with benign prostatic hypertrophy. The questionnaire was used to interview 48 men with benign prostatic hypertrophy being placed on waiting lists for transurethral resection of the prostate at four Victorian public hospitals. Individual patient case vignettes were produced using the answers to the interview questions. Members of an assessor panel comprising six laypeople, six non-urologist medical practitioners, and five urologists individually reviewed the vignettes and assigned urgency ratings and rankings to each patient. The urgency ratings and rankings were used to derive weightings for the clinical and psychosocial factors that were then incorporated into a prioritization tool framework. RESULTS: The assessor panel perceived a broad spread of urgency for surgery among the patients. Agreement on rankings and urgency ratings was moderate among assessors. Linear regression showed that the effect of clinical symptoms and psychosocial disturbance held approximately equal-strength independent associations with perceived urgency for all groups of assessors. CONCLUSION: Urologists, non-urologist medical practitioners and laypeople considered the severity of benign prostatic hypertrophy symptoms and any resulting psychosocial disturbance as equally important in establishing priority for transurethral resection of the prostate. New prioritization tools should take both into consideration and weight them equally.

Factors predicting for urinary morbidity following 125iodine transperineal prostate brachytherapy.

PURPOSE: To assess factors related to the risk of acute urinary retention and other morbidity indices in patients undergoing transperineal seed implantation of the prostate. MATERIALS AND METHODS: One hundred and seventy-three consecutive patients treated with (125)Iodine transperineal interstitial permanent prostate brachytherapy (TIPPB) were evaluated. Various demographic, pathological, symptomatic, urodynamic and dosimetric values were assessed in relation to the incidence of acute urinary retention as well as the International Prostate Symptom Score (IPSS) dynamics. Patients were routinely placed on alpha-blockade postimplant. Dosimetry was based on CT scan one month postimplant. RESULTS: Acute urinary retention developed in thirty-four patients (19.7%), at a median time of four days. Peak urinary flow rate was the only independent factor which varied significantly between those suffering retention and those not (median of 16 and 19.5 ml/s respectively, P=0.005). Median preimplant IPSS was 4.0, with a median peak of 16 at 3 months. Actuarial median time to return to baseline IPSS was at 15 months. The peak IPSS above preimplant levels was correlated significantly in multivariate analysis with the number of seeds implanted superior to the physician-nominated anatomical base level of the prostate (P<0.009), as well as lower preimplant IPSS values. CONCLUSIONS: In our series, preimplant urinary flow rate was the most important factor predictive of postimplant acute urinary retention. The patients' risk of having heightened IPSS change following implantation was correlated to a lower preimplant IPSS and an increased number of seeds implanted above the level of the prostatic base, possibly reflecting bladder base rather than urethral irritation in the development of acute urinary morbidity.

What to do for prostate cancer patients with a rising PSA?--A survey of Australian practice.

PURPOSE: To document current Australian management of asymptomatic prostate cancer patients with prostate-specific antigen (PSA) relapse after radical treatment or considered unsuitable for radical treatment. MATERIALS AND METHODS: Four case scenarios-postprostatectomy PSA relapse, postradiotherapy (RT) with a slow or a rapidly rising PSA level, or no radical treatment-were presented. Management preferences, including (where relevant) RT, androgen ablation either immediate or delayed until a PSA rise or symptomatic progression, and other approaches, were identified. The preferred methods of androgen ablation were noted. RESULTS: One hundred eighteen informative replies out of 324 e-mailed surveys were received. For postprostatectomy PSA relapse, 59% of respondents favored salvage RT. For post-RT with a slow or a rapidly rising PSA level and treatment of nonradical patients, there was no clear consensus of opinion, with respondents divided among the different options. A diverse range of PSA levels was cited for delayed intervention, with values ranging from 0.8 to 100 ng/mL. PSA doubling time proved a more consistent criterion for determining intervention. Most respondents favored the use of a luteinizing hormone-releasing hormone agonist as first-line androgen ablation, although patient choice was recognized as important in all decision making. CONCLUSIONS: A lack of available evidence underlies the diversity of opinion regarding the management of asymptomatic prostate cancer patients with a rising PSA. The need for randomized controlled trials in this area is highlighted.