John Yaxley

Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: A randomized controlled trial

Objective  To report the first systematic investigation of the cognitive effects of luteinizing hormone‐releasing hormone (LHRH) analogues in male patients, as LHRH analogues have been associated with memory impairments in women using these drugs for gynaecological conditions.

Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study.

BACKGROUND The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in uro-oncology. We aimed to compare these two approaches in terms of functional and oncological outcomes and report the early postoperative outcomes at 12 weeks. METHOD In this randomised controlled phase 3 study, men who had newly diagnosed clinically localised prostate cancer and who had chosen surgery as their treatment approach, were able to read and speak English, had no previous history of head injury, dementia, or psychiatric illness or no other concurrent cancer, had an estimated life expectancy of 10 years or more, and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Womens Hospital (Brisbane, QLD). Participants were randomly assigned (1:1) to receive either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy. Randomisation was computer generated and occurred in blocks of ten. This was an open trial; however, study investigators involved in data analysis were masked to each patients condition. Further, a masked central pathologist reviewed the biopsy and radical prostatectomy specimens. Primary outcomes were urinary function (urinary domain of EPIC) and sexual function (sexual domain of EPIC and IIEF) at 6 weeks, 12 weeks, and 24 months and oncological outcome (positive surgical margin status and biochemical and imaging evidence of progression at 24 months). The trial was powered to assess health-related and domain-specific quality of life outcomes over 24 months. We report here the early outcomes at 6 weeks and 12 weeks. The per-protocol populations were included in the primary and safety analyses. This trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12611000661976. FINDINGS Between Aug 23, 2010, and Nov 25, 2014, 326 men were enrolled, of whom 163 were randomly assigned to radical retropubic prostatectomy and 163 to robot-assisted laparoscopic prostatectomy. 18 withdrew (12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy); thus, 151 in the radical retropubic prostatectomy group proceeded to surgery and 157 in the robot-assisted laparoscopic prostatectomy group. 121 assigned to radical retropubic prostatectomy completed the 12 week questionnaire versus 131 assigned to robot-assisted laparoscopic prostatectomy. Urinary function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (74·50 vs 71·10; p=0·09) or 12 weeks post-surgery (83·80 vs 82·50; p=0·48). Sexual function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (30·70 vs 32·70; p=0·45) or 12 weeks post-surgery (35·00 vs 38·90; p=0·18). Equivalence testing on the difference between the proportion of positive surgical margins between the two groups (15 [10%] in the radical retropubic prostatectomy group vs 23 [15%] in the robot-assisted laparoscopic prostatectomy group) showed that equality between the two techniques could not be established based on a 90% CI with a Δ of 10%. However, a superiority test showed that the two proportions were not significantly different (p=0·21). 14 patients (9%) in the radical retropubic prostatectomy group versus six (4%) in the robot-assisted laparoscopic prostatectomy group had postoperative complications (p=0·052). 12 (8%) men receiving radical retropubic prostatectomy and three (2%) men receiving robot-assisted laparoscopic prostatectomy experienced intraoperative adverse events. INTERPRETATION These two techniques yield similar functional outcomes at 12 weeks. Longer term follow-up is needed. In the interim, we encourage patients to choose an experienced surgeon they trust and with whom they have rapport, rather than a specific surgical approach. FUNDING Cancer Council Queensland.

Micropapillary urothelial carcinoma of the urinary bladder: a clinicopathological analysis of 72 cases

Aim: Micropapillary carcinoma (MPC) of the bladder is an aggressive variant of urothelial carcinoma (UC). It is unknown if any amount of a micropapillary component justifies the diagnosis of MPC. It is also unknown if surface MPC also has aggressive potential. Methods: We studied 72 patients with UC with a micropapillary component in transurethral resections of bladder (TURB) diagnosed between 1998 and 2008. Fifty‐seven patients were treated with radical cystectomy. Tumours were classified according to pathological (pT) stage and percentage of MPC (≤10%, 10–49%, 50–100%). This was correlated with clinical data and follow up. Significant factors in univariate analysis were entered into a multivariate analysis. Results: In the TURB specimens, 12 had pTa, 33 pT1 and 27 pT2 tumours with 23% also displaying urothelial carcinoma in situ (CIS). On cystectomy, the MPC component was upstaged in 79% of cases. Twenty‐five (35%) patients had metastases at presentation or nodal metastases at cystectomy and 27 patients (38%) died of disease. Mean survival was 17.8 months. Of 12 pTa MPC cases, eight were treated with cystectomy, all displaying invasive carcinoma including five (62%) with pT2–pT4 disease. Three (25%) of these patients died of disease. Seven patients had a MPC component of <10% all of whom had cystectomy. Six of these had invasive carcinoma including two (33%) with pT2–pT4 disease. One (15%) of these patients died of disease. On univariate analysis, the proportion of the MPC component on TURB and pathological stage predicted disease specific survival (p = 0.01 and 0.004, respectively), while presence of CIS predicted recurrence (p = 0.03). On multivariate analysis, CIS predicted recurrence (p = 0.003); however, the proportion of MPC in TURB did not remain significant in predicting disease specific survival. The pathological stage of MPC remained significant in predicting disease specific survival (p = 0.04). Conclusions: Any amount of MPC, even <10% is significant in urothelial carcinoma and should be reported. Surface MPC is associated with invasive carcinoma in most cases which can be high stage. Adequate sampling to include detrusor muscle is crucial in these cases. Associated CIS is important to be recognised and reported as this also impacts on clinical outcome.

Any proportion of ductal adenocarcinoma in radical prostatectomy specimens predicts extraprostatic extension

Ductal adenocarcinoma of the prostate is an aggressive malignancy, often presenting at an advanced stage. In mixed ductal and acinar adenocarcinomas, the relationship between the proportion of the ductal component of the tumor and the pathologic stage and whether or not aggressive behavior is simply a function of grade remains undetermined. From 268 consecutive radical prostatectomies undertaken as a curative procedure for clinical localized prostate cancer, we identified 34 cases (12.7%) with ductal adenocarcinoma of the prostate comprising 5% to 100% of the total tumor volume. For cases with a ductal adenocarcinoma of the prostate component, the mean age at diagnosis of 60 years (range 49-69 years), mean serum prostate-specific antigen of 8.4 ng/mL (range, 0.8-21 ng/mL) and positive surgical margin rate of 17.6% did not differ significantly from that of the pure adenocarcinoma group. All 34 patients with ductal adenocarcinoma of the prostate had peripheral zone involvement while 16 (46%) also had transition zone involvement. Twenty-five (73%) cases with ductal adenocarcinoma of the prostate had extraprostatic extension (pT3), which compared to 32.9% with acinar adenocarcinoma. The presence of ductal adenocarcinoma of the prostate (P < .0001), high tumor volume (P = .001) and Gleason score >7 (P = .04) significantly predicted pT3 staging category, and the presence of ductal adenocarcinoma of the prostate remained a significant predictor for pT3, after adjusting for tumor volume and Gleason score >7. The proportion of ductal adenocarcinoma of the prostate did not significantly modify the strength of the observed association with pathological stage. In view of the significant association with extraprostatic extension we would recommend that in both core biopsies and radical prostatectomy specimens any proportion of ductal adenocarcinoma of the prostate should be reported.

The use of (68 ) Ga-PSMA PET CT in men with biochemical recurrence after definitive treatment of acinar prostate cancer.

Early localisation of disease recurrence after definitive treatment of prostate cancer is vital to determine suitability for salvage treatment. Our aim was to further investigate the relationship between prostate specific antigen (PSA) level and detection of suspected cancer recurrence using 68 Ga‐PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy (RP) or radiotherapy, particularly at low PSA levels.

The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer

Summary The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters. Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32–79 years). Median serum prostate specific antigen was 5.9 (range 0.4–69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1–5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS. This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

A randomised trial of robotic and open prostatectomy in men with localised prostate cancer

BackgroundProstate cancer is the most common male cancer in the Western world however there is ongoing debate about the optimal treatment strategy for localised disease. While surgery remains the most commonly received treatment for localised disease in Australia more recently a robotic approach has emerged as an alternative to open and laparoscopic surgery. However, high level data is not yet available to support this as a superior approach or to guide treatment decision making between the alternatives. This paper presents the design of a randomised trial of Robotic and Open Prostatectomy for men newly diagnosed with localised prostate cancer that seeks to answer this question.Methods/design200 men per treatment arm (400 men in total) are being recruited after diagnosis and before treatment through a major public hospital outpatient clinic and randomised to 1) Robotic Prostatectomy or 2) Open Prostatectomy. All robotic prostatectomies are being performed by one surgeon and all open prostatectomies are being performed by one other surgeon. Outcomes are being measured pre-operatively and at 6 weeks and 3, 6, 12 and 24 months post-surgery. Oncological outcomes are being related to positive surgical margins, biochemical recurrence +/− the need for further treatment. Non-oncological outcome measures include: pain, physical and mental functioning, fatigue, summary (preference-based utility scores) and domain-specific QoL (urinary incontinence, bowel function and erectile function), cancer specific distress, psychological distress, decision-related distress and time to return to usual activities. Cost modelling of each approach, as well as full economic appraisal, is also being undertaken.DiscussionThe study will provide recommendations about the relative benefits of Robotic and Open Prostatectomy to support informed patient decision making about treatment for localised prostate cancer; and to assist in treatment services planning for this patient group.Trial registrationACTRN12611000661976

A progress report on a prospective randomised trial of open and robotic prostatectomy

A randomised trial of robotic and open prostatectomy commenced in October 2010 and is progressing well. Clinical and quality of life outcomes together with economic costs to individuals and the health service are being examined critically to compare outcomes.

Brachytherapy‐ State Of The Art Radiotherapy In Prostate Cancer

Radiation Oncology Victoria, Ringwood East, Vic., Australia, *Prostate Cancer Center of Seattle, Seattle, WA, USA, Wesley Hospital, Brisbane, Qld , St Vincent’s Hospital, Darlinghurst, NSW, Radiation Oncology Victoria, Epping, Department of Surgery and Olivia Newton John Cancer Research Institute, Austin Hospital, and **Department of Surgical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia

Cost-effectiveness analysis of multiparametric MRI with increased active surveillance for low-risk prostate cancer in Australia

To evaluate the cost‐effectiveness of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer and direct all low‐risk patients into active surveillance (AS).