Ross Snow

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.

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.

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.

To compare perioperative, renal and oncological outcomes after robotic‐assisted partial nephrectomy (RAPN) versus open partial nephrectomy (OPN) for the treatment of renal tumours.

MP38-06 ZERO HOSPITAL ADMISSIONS FOR INFECTION AFTER 1359 TRANSPERINEAL PROSTATE BIOPSIES

INTRODUCTION AND OBJECTIVES: Transrectal biopsy is plagued by an increasing rate of serious infection, despite use of recommended fluoroquinolone antibiotics. Transperineal biopsy (TPB), on the other hand, has been associated with an exceedingly low rate of serious infection. The aim of this study was to determine the rate of hospital admissions for infection after transperineal biopsy of prostate. METHODS: Patients underwent transperineal biopsy of the prostate (TPB) between May 2012 and October 2016 by a private group urology practice, at multiple hospitals across Melbourne. A standard brachytherapy template grid was used, taking a number of samples from left and right prostate posterior, mid and anterior regions. Some patients had extra core biopsies taken from target areas suspicious of cancer identified on prior MRI. Data collected from these patients were entered into an ethics approved prospective database including prophylactic antibiotics used and post operative complications. RESULTS: 1359 consecutive patients underwent TPB. Initially patients were treated with quinolone prophylaxis and then later patients received cephazolin only. 1030 (75.8%) had single dose IV cephazolin, 388 (28.6%) had an oral quinolone with IV cephazolin, 107 (7.9%) had IV ceftriaxone and 2 (0.1%) had IV clindamycin, 2 (0.1%) had IV meropenem and 1 (0.1%) had IV vancomycin prophylaxis. Routine practice shifted from use of quinolones to cephazolin during the study period. 25 (1.8%) patients developed acute urinary retention and 1 patient was treated in the community with oral antibiotics for prostatitis. No patients were readmitted to hospital with infection. CONCLUSIONS: Sepsis post TPB is an exceedingly rare complication, with a 0% rate in this large prospective multicentre cohort. It is safe to use single dose cephazolin only as antibiotic prophylaxis prior to TPB, negating the need for quinolones. This study supports the current Australian Therapeutic Guidelines recommendation for TPB prophylaxis. Whether any antibiotic prophylaxis is needed at all for TPB is the subject of a future study.