68Ga-PSMA PET/CT tumour intensity pre-operatively predicts adverse pathological outcomes and progression-free survival in localised prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) improves prostate cancer staging. Intraprostatic PSMA intensity may predict clinically relevant oncological outcomes. The aim of this study was to investigate the relationship between intraprostatic PSMA intensity and adverse pathology outcomes, including biochemical progression-free survival (PFS) after radical prostatectomy. METHODS: This is a cohort study of 71 patients with MRI-guided, biopsy-proven prostate cancer and pre-operative 68Ga-PSMA-11 PET/CT prior to radical prostatectomy (RP). Intraprostatic PSMA intensity was correlated to adverse pathology outcomes (Gleason score and upgrading from biopsy, pathological stage) and PFS using multivariate statistical analysis. RESULTS: 68Ga-PSMA-11 PET/CT intensity in vivo predicted all of Gleason score on RP, upgrading from biopsy to RP histopathology, pathological stage, positive surgical margins and PFS. 74.6% (53/71) of patients were free from progression at a median follow-up of 19.5 months (0.4-48 months). Predictive accuracy was particularly enhanced by PSMA among patients with biopsy Gleason score ≤ 3 + 4 (n = 39) as the most significant predictor of PFS according to Cox-proportional hazards regression. Cox-regression adjusted survival analysis predicted a 5.48-fold increase in hazard for Gleason score ≤ 3 + 4 patients with high (SUVmax > 8) compared with low (SUVmax < 8) PSMA intensity. CONCLUSION: Intraprostatic 68Ga-PSMA-11 intensity is prognostic and may be a valuable new biomarker in localised prostate cancer, especially in men with biopsy-proven Gleason 3 + 4 disease considering an initial approach of active surveillance or focal therapy.

Histological comparison between predictive value of preoperative 3-T multiparametric MRI and 68 Ga-PSMA PET/CT scan for pathological outcomes at radical prostatectomy and pelvic lymph node dissection for prostate cancer.

OBJECTIVE: To evaluate the ability of preoperative multiparametric magnetic resonance imaging (mpMRI) and a gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) scan to predict pathological outcomes and also identify a group of men with a <5% risk of histological pelvic lymph node metastasis (LNM) at pelvic lymph node dissection (PLND) performed during a robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer. We then aimed to compare these results to known risk calculators for LNM, including the Cancer of the Prostate Risk Assessment (CAPRA) score, Memorial Sloan Kettering Cancer Centre (MSKCC) and Briganti nomograms. PATIENTS AND METHODS: Between July 2014 and September 2019 only men who had both a preoperative mpMRI and staging 68 Ga-PSMA PET/CT at our institution followed by a RALP with PLND referred to a single specialist uropathology laboratory were considered for inclusion. The data were collected retrospectively prior to February 2019 and in a prospective manner thereafter. A model was built to allocate probabilities of the men with a negative 68 Ga-PSMA PET/CT scan having a <5% risk of histologically LNM at RALP based on the preoperative radiological staging. RESULTS: A total of 233 consecutive men met the inclusion criteria of which 58 men (24.9%) had a LNM identified on PLND histology. The median (range) International Society of Urological Pathology (ISUP) Grade was 5 (1-5) and the median (range) prostate-specific antigen level was 7.4 (1.5-72) ng/mL. The median (range) number of resected lymph nodes was 16 (1-53) and the median (range) number of positive nodes identified on histology was 2 (1-22). Seminal vesicle invasion on mpMRI was more common in node-positive men than in the absence of LNM (31% vs 12%). The maximum standardised uptake value of the primary tumour on 68 Ga-PSMA PET/CT was higher in men with LNM (median 9.2 vs 7.2, P = 0.02). Suspected LNM were identified in 42/233 (18.0%) men with 68 Ga-PSMA PET/CT compared with 22/233 (9.4%) men with mpMRI (P = 0.023). The positive and negative predictive value for 68 Ga-PSMA PET/CT was 66.7% and 84.3% respectively, compared to 59.1% and 78.7% for mpMRI. A predictive model showed only two men (4.2%) with a negative preoperative 68 Ga-PSMA PET/CT would be positive for a histological LNM if they are ISUP Grade < 5 and Prostate Imaging-Reporting and Data System (PI-RADS) <5; or ISUP Grade 5 with PI-RADS < 4. An inspection of three additional variables: CAPRA score, MSKCC and Briganti nomograms did not improve the predictive probability for this group. However, of the 61 men with ISUP Grade 4-5 malignancy and also a PI-RADS 5 mpMRI, 20 (32.8%) men had a microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT. CONCLUSION: Preoperative 68 Ga-PSMA/PET CT was more sensitive in identifying histological pelvic LNM than 3-T mpMRI. Men with a negative 68 Ga-PSMA PET/CT have a lower risk of LNM than predicted with CAPRA scores or MSKCC and Briganti nomograms. We identified that the combination of a negative preoperative 68 Ga-PSMA PET/CT, ISUP biopsy Grade <5 and PI-RADS <5 prostate mpMRI, or an ISUP Grade 5 with PI-RADS <4 on mpMRI was associated with a <5% risk of a LNM. The addition of CAPRA scores, MSKCC and Briganti nomograms did not improve the predictive probability within this model. Conversely, men with ISUP Grade 4-5 malignancy associated with a PI-RADS 5 prostate mpMRI had a >30% risk of microscopic LNM despite a negative preoperative 68 Ga-PSMA PET/CT and this high-risk group would appear suitable for an extended PLND at the time of a radical prostatectomy.

68Ga-PSMA PET/CT better characterises localised prostate cancer after MRI and transperineal prostate biopsy: Is 68Ga-PSMA PET/CT guided biopsy the future?

BACKGROUND: 68Ga prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) may be superior to multiparametric MRI (mpMRI) for localisation of prostate cancer tumour foci, however the concordance and differences between 68Ga-PSMA PET/CT and mpMRI when applied to all biopsied patients and potential benefit in patients with negative mpMRI is unclear. METHODS: Retrospective analysis of patients undergoing mpMRI, prostate biopsy and 68Ga-PSMA PET/CT over a 3-year period. Diagnostic performance of 68Ga-PSMA PET/CT and mpMRI were assessed using biopsy histopathology for the entire cohort and radical prostatectomy specimen in a subset of patients. Lesion concordance and additional detection of each modality were determined, including in a dedicated cohort of patients with mpMRI PIRADS 2 scans. RESULTS: A total of 144 patients were included in the study. Index lesion/foci detection was similar between 68Ga-PSMA PET/CT and mpMRI (sensitivity 83.1% vs 90.1%; p = 0.267), however lesions missed by mpMRI were larger (1.66 cm3 vs 0.72 cm3; p = 0.034). Lesion detection rates were similar across the biopsy histopathology and radical prostatectomy specimen subset, with a high concordance for index (80.1%) and a moderate concordance for total (67%) lesions between the 2 imaging modalities. The additional detection yield favoured 68Ga-PSMA PET/CT over mpMRI for index (13.5% vs 4.3%) and total (18.2% vs 5.4%) lesions; both modalities missed 2.1% and 12.3% of index and total lesions, respectively. 68Ga-PSMA PET/CT identified 9 of 11 patients with PIRADS 2 mpMRI but subsequently diagnosed with Gleason ≥ 3 + 4 disease. CONCLUSIONS: Despite high concordance rates, 68Ga-PSMA PET/CT incrementally improved tumour localisation compared with mpMRI. These results suggest that 68Ga-PSMA PET/CT may have an incremental value to that of mpMRI in the diagnostic process for prostate.

Use of a trizonal schema to assess targeting accuracy in prostatic fusion biopsy.

OBJECTIVES: To describe the use of a novel 'trizonal' biopsy schema in which 'near-target' biopsies are taken adjacent to the MRI lesion, in addition to target and systematic biopsies, to determine the accuracy of prostate MRI fusion systems. PARTICIPANTS AND METHODS: A trizonal biopsy technique was used to evaluate 75 men with small Prostate Imaging Reporting and Data System (PI-RADS) 3-5 MRI lesions (<15 mm) identified from a prospective cohort of 290 men undergoing multiparametric magnetic resonance imaging (MRI) for suspected prostate cancer at a single high-volume institution between September 2017 and May 2019. In addition to target and systematic biopsies, near-target biopsies were taken 4 mm from the apparent border of the MRI lesion. Comparisons were made between highest International Society of Urological Pathology grade and longest tumour length. RESULTS: Fifty-three men with significant prostate cancer in the same quadrant as the target were included in the final analysis. The percentages of positive cores from target, near-target and MRI-negative zones were 66%, 39% and 17%, respectively. Significant cancer was detected in the near-target zone in 77% of cases when the target zone was positive. A total of 17% of participants were upgraded by a median (range) of 1 (1-3) grades through the addition of near-target cores. Notably, 9% of men were diagnosed with clinically significant prostate cancer solely via the near-target biopsy cores when the target cores were negative. CONCLUSION: The use of near-target biopsies as part of a trizonal biopsy schema provides a novel methodology to optimize clinically significant prostate cancer detection.

Improved detection and reduced biopsies: the effect of a multiparametric magnetic resonance imaging-based triage prostate cancer pathway in a public teaching hospital.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves clinically significant prostate cancer (csPCa) detection by facilitating targeted biopsy (cognitive, fusion technology, or in-gantry MRI guidance) and reducing negative biopsies. This study sought to describe the feasibility of introducing an mpMRI-based triage pathway, including diagnostic performance, applicability to training, and cost analysis. METHODS: An observational retrospective cohort study of consecutive patients attending a large public tertiary referral training hospital who underwent mpMRI for suspicion of prostate cancer was considered. Standard clinical, MRI-related, histopathological, and financial parameters were collected for analysis of biopsy avoidance, diagnostic accuracy of biopsy approach, and operator (consultant and resident/registrar) and logistical (including financial) feasibility. RESULTS: 653 men underwent mpMRI, of which 344 underwent prostate biopsy resulting in a 47% biopsy avoidance rate. Overall, 240 (69.8%) patients were diagnosed with PCa, of which 208 (60.5%) were clinically significant, with higher rates of csPCa observed for higher PIRADS scores. In patients who underwent both systematic and targeted biopsy (stTPB), targeted cores detected csPCa in 12.7% and 16.6% in more men than systematic cores in PIRADS 5 and 4, respectively, whereas systematic cores detected csPCa in 5% and 3.2% of patients, where targeted cores did not. A high standard of performance was maintained across the study period and the approach was shown to be cost effective. CONCLUSIONS: Introdution of an mpMRI-based triage system into a large public tertiary teaching hospital is feasible, cost effective and leads to high rates of prostate cancer diagnosis while reducing unnecessary biopsies and detection of insignificant PCa.

Comparison of dynamic features of pelvic floor muscle contraction between men with and without incontinence after prostatectomy and men with no history of prostate cancer.

AIM: To compare features of pelvic floor muscle function between men with and without incontinence after prostatectomy and men with no history of prostate cancer. METHODS: The study included men with incontinence postprostatectomy (PPI; n = 20), continent men postprostatectomy (PPC; n = 23) and a control group (CC; n = 20). Transperineal ultrasound imaging recorded motion associated with contraction of the striated urethral sphincter (SUS), puborectalis (PR) and bulbocavernosus (BC) muscles during maximal voluntary contraction (MVC), submaximal efforts, evoked coughing and bearing down. Anatomical landmark displacements were compared between groups and receiver operating characteristics were calculated to determine the threshold displacements that best differentiated PPI and PPC. RESULTS: PPC demonstrated greater SUS, PR, and BC displacement than PPI during MVC (All: P < .01). During cough, PPC had less bladder neck descent (PR lengthening), and greater BC shortening (P = .003) than both PPI and CC. PPC also achieved greater SUS displacement (P = .025) than PPI during cough. The best discrimination between PPI and PPC was achieved when men exceeded threshold displacement for both SUS (≥4.1 mm) and PR (≥2.4 mm) during MVC. The urethral length was not different between PPC and PPI. CONCLUSIONS: Men who were continent postprostatectomy achieved greater shortening of the SUS, PR, and BC muscles than incontinent men during voluntary contractions and demonstrated better PR and BC function than control participants during coughing. The capacity to shorten the SUS ≥4.1 mm and the PR ≥2.4 mm best distinguished between PPI and PPC and might be a useful clinical target for conservative treatment programs.

Outcomes of Primary Lymph Node Staging of Intermediate and High Risk Prostate Cancer with 68Ga-PSMA Positron Emission Tomography/Computerized Tomography Compared to Histological Correlation of Pelvic Lymph Node Pathology.

PURPOSE: The majority of men who undergo pelvic lymph node dissection at radical prostatectomy have benign lymph node histology. The aim of this study was to assess the predictive value of preoperative 68Ga-PSMA (prostate specific membrane antigen) positron emission tomography/computerized tomography to predict histological metastasis on pelvic lymph node dissection performed during radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the sensitivity, specificity, and positive and negative predictive values of preoperative staging 68Ga-PSMA positron emission tomography/computerized tomography to identify histological lymph node metastasis in 208 consecutive men who subsequently proceeded with pelvic lymph node dissection at radical prostatectomy. RESULTS: Median prostate specific antigen was 7.6 µg/l, the lymph node count was 13 and Gleason score was 4 + 5. On a per patient basis only 21 of the 55 men with metastasis on histological examination were identified on 68Ga-PSMA positron emission tomography/computerized tomography for 38.2% sensitivity. Of the 143 men with no lymph node metastasis on 68Ga-PSMA imaging 34 had metastasis on histology for 80.8% negative predictive value. Specificity was 93.5% and positive predictive value was 67.7%. For the 172 histologically identified malignant lymph node metastases the sensitivity per node was 24.4% and specificity was 99.5%. CONCLUSIONS: If negative 68Ga-PSMA positron emission tomography/computerized tomography is used as the basis of not performing pelvic lymph node dissection, 80% of men would avoid unnecessary pelvic lymph node dissection. However, 68Ga-PSMA positron emission tomography/computerized tomography has poor sensitivity per node to detect all histologically positive lymph node metastases. Thus, pelvic lymph node dissection remains the gold standard to stage pelvic lymph nodes despite its known limitations and complications.

Assessment of tumour-associated necrosis provides prognostic information additional to World Health Organization/International Society of Urological Pathology grading for clear cell renal cell carcinoma.

AIMS: The aims of this study were to evaluate the impact of tumour-associated necrosis (TAN) on metastasis-free survival for clear cell renal cell carcinoma (RCC), and to determine whether TAN provides survival information additional to World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading. METHODS AND RESULTS: The study consisted of 376 cases of clear cell RCC treated by nephrectomy, for which follow-up was available. WHO/ISUP grade was assigned, and sections were assessed for the presence of TAN. American Joint Committee on Cancer (AJCC) pT staging category and tumour size were also recorded. The development of metastatic disease was taken as the clinical endpoint, and survival analyses, utilising univariate and multivariate models, were performed. WHO/ISUP grades were: grade 1, 35 cases (9.3%); grade 2, 188 cases (50.0%); grade 3, 91 cases (24.2%); and grade 4, 62 cases (16.5%). Staging categories were pT1-pT2 [234 tumours (62.2%)] and pT3-pT4 [139 tumours (37.0%)]. TAN was seen in 128 cases (34.0%). Neither TAN nor metastases were seen in grade 1 tumours. Among grade 2-4 tumours, those with TAN had a significantly worse prognosis than those without TAN (P = 0.017, P = 0.04, and P = 0.006, respectively). Multivariate analysis (WHO/ISUP grade, pT staging category, and TAN) showed all three variables to be independently associated with outcome (P = 0.009, P = 0.005, and P = 0.001, respectively). For all tumour grades and pT staging categories, it was found that the presence of TAN was associated with a 2.91-fold greater risk of metastatic disease. CONCLUSION: Tumour-associated necrosis is an important prognostic factor for clear cell RCC, independently of WHO/ISUP grade. This supports the suggestion that TAN could be incorporated into tumour grading criteria.

Improved specificity with 68Ga PSMA PET/CT to detect clinically significant lesions "invisible" on multiparametric MRI of the prostate: a single institution comparative analysis with radical prostatectomy histology.

PURPOSE: Positron emission tomography (PET) for prostate-specific membrane antigen (PSMA) represents a promising method for prostate cancer diagnosis and staging. Comparisons of PSMA-based tumour characterisation to multiparametric MRI (mpMRI) are limited, hence this study sought to compare the diagnostic accuracy of 68Ga-PSMA PET/CT to mpMRI against radical prostatectomy (RP) whole gland histopathology. METHODS: A retrospective cohort study of consecutive patients who underwent pre-operative mpMRI and 68Ga-PSMA PET/CT followed by a RP was performed. Standard clinical parameters were collected. "Per patient" and "per lesion" analyses for image-based detection according to RP histopathology were described using sensitivity, specificity and other measures of diagnostic accuracy. RESULTS: Fifty-eight patients (median age 65.5 years, median PSA 7.35 ng/mL) underwent RP, resulting in a high-risk cohort (≥pT3 69%). Sensitivities for identification of index lesion, bilateral and multifocal disease were 90%, 21%, 19% for mpMRI and 93%, 42%, 34% for 68Ga-PSMA PET/CT. Histology analyses revealed 88 cancer foci of Gleason grades 3 + 3 (4%), 3 + 4 (64%), 4 + 3 (19%), 4 + 4 (3%) and ≥ 4 + 5 (10%), of which 68Ga-PSMA PET/CT correctly detected more foci (78%, AUC 0.817) than mpMRI (69%, AUC 0.729). CONCLUSIONS: 68Ga-PSMA PET/CT may better reflect RP histopathology compared to mpMRI when considering multifocal and bilateral disease. These findings may influence surgical planning, targeted biopsy and focal therapy strategies and require further research.

Changing clinical trends in 10 000 robot-assisted laparoscopic prostatectomy patients and impact of the 2012 US Preventive Services Task Force's statement against PSA screening.

OBJECTIVES: To evaluate the clinical trend changes in our robot-assisted laparoscopic prostatectomy (RALP) practice and to investigate the effect of 2012 US Preventive Services Task Force (USPSTF) statement against PSA screening on these trends. PATIENTS AND METHODS: Data of 10 000 RALPs performed by a single surgeon between 2002 and 2017 were retrospectively analysed. Time trends in successive 1000 cases for clinical, surgical and pathological characteristics were analysed with linear and logistic regression. Time-trend changes before and after the USPSTF's statement were compared using a logistic regression model and likelihood-ratio test. RESULTS: Unfavourable cancer characteristics rate, including D'Amico high risk, pathological non-organ-confined disease and Gleason score ≥4+4 increased from 11.5% to 23.3%, 14% to 42.5%, and 7.7% to 20.9%, respectively, over time (all P < 0.001). Significant time-trend changes were detected after the USPSTF's statement with an increase in the positive trend of Gleason ≥4+4 and increase in the negative trends of Gleason ≤3+4 tumours. There was a significant negative trend in the rate of full nerve-sparing (NS) with a decrease from 59.3% to 35.7%, and a significant positive trend in partial NS with an increase from 15.8% to 62.5% over time (both P < 0.001). The time-trend slope in 'high-grade' partial NS significantly decreased and 'low-grade' partial NS significantly increased after the USPSTF's statement. The overall positive surgical margin rate increased from 14.6% to 20.3% in the first vs last 1000 cases (P < 0.001), with a significant positive slope after the USPSTF's statement. CONCLUSIONS: The proportion of high-risk patients increased in our series over time with a significant impact of the USPSTF's statement on pathological time trends. This stage migration resulted in decreased utilisation of high-quality NS and increased performance of poor-quality NS.

Risk of metastatic disease on 68 gallium-prostate-specific membrane antigen positron emission tomography/computed tomography scan for primary staging of 1253 men at the diagnosis of prostate cancer.

OBJECTIVE: To determine the number of men with 68 gallium-prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) avid metastasis at diagnosis, as most data on 68 Ga-PSMA PET/CT are for the evaluation of recurrent disease after primary treatment and to our knowledge this study is the largest series of primary prostate cancer staging with 68 Ga-PSMA PET/CT. PATIENTS AND METHODS: A retrospective review conducted on 1253 consecutive men referred by urologists or radiation oncologists to our tertiary referral centre for 68 Ga-PSMA PET/CT scan for staging at the initial diagnosis of prostate cancer between July 2014 and June 2018. The primary outcome measure was to determine the risk of metastasis based on 68 Ga-PSMA PET/CT. Patients were risk stratified based on histological biopsy International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) level, and staging with pre-biopsy multiparametric magnetic resonance imaging (mpMRI). Univariate and multivariate logistic regression were used to analyse results. RESULTS: The median PSA level was 6.5 ng/mL and median ISUP grade was 3, with high-risk disease in 49.7%. The prostate primary was PSMA avid in 91.7% of men. Metastatic disease was identified in 12.1% of men, including 8.2% with a PSA level of <10 ng/mL and 43% with a PSA level of >20 ng/mL. Metastases were identified in 6.4% with ISUP grade 2-3 and 21% with ISUP grade 4-5. Pre-biopsy mpMRI identified metastasis in 8.1% of T2 disease, increasing to 42.4% of T3b. Lymph node metastases were suspected in 107 men, with 47.7% outside the boundaries of an extended pelvic lymph node dissection. Skeletal metastases were identified in 4.7%. In men with intermediate-risk prostate cancer, metastases were identified in 5.2%, compared to 19.9% with high-risk disease. CONCLUSIONS: These results support the use of 68 Ga-PSMA PET/CT for primary staging of prostate cancer. Increasing PSA level, ISUP grade and radiological staging with mpMRI were all statistically significant prognostic factors for metastasis on both univariate and multivariate analysis.

MRI-guided in-bore biopsy for prostate cancer: what does the evidence say? A case series of 554 patients and a review of the current literature.

PURPOSE: To review our experience with MRI-guided in-bore prostate biopsy (MRGB) and present a review of the literature on MRGB. METHODS: A retrospective review of patients presenting for MRGB between 2013 and 2018. Diagnostic and biopsy MRI scans were reviewed to collect data on scan dates, procedure times, characteristics of MRI targets (PI-RADS™ score, target size, ADC value and location). A review of the literature on MRGB for the period 2013-2018 was performed. RESULTS: 607 targets in 554 men were biopsied. Overall and significant cancer detection rate were 80% and 55% at a patient level, and 76 and 59% at the target level, respectively. Prostate cancer (CaP) detection in men with prior negative biopsy was 60% while 50% of men on active surveillance were upgraded to clinically significant disease (CSD). Lesion location did not predict for presence of CaP or CSD. PI-RADS™ score, age and PSAD were predictors of CSD at biopsy on multivariate analysis. Literature review identified 23 reports reporting on MRGB cohorts (~ 4000 patients). Overall cancer detection ranged from 23 to 74% and CSD in 63% overall. CaP detection in PI-RADS™ 3 targets was substantially lower in our series and the literature than for PI-RADS™ 4-5 targets. CONCLUSIONS: MRGB in PI-RADS™ 3-5 targets yields high rates of cancer diagnosis. High detection rates are also seen in men with prior negative biopsy and AS cohorts. PI-RADS™ score, age and PSAD can reliably predict CSD detection. The number of published series is small and the role of MRGB in PI-RADS™ 3 targets needs further study.

Is postoperative Doppler ultrasonography useful for the early detection of asymptomatic pseudoaneurysm and prevention of haemorrhagic complications after partial nephrectomy?

OBJECTIVE: To assess the clinical utility of systematic Doppler ultrasonography (DUS) after robot-assisted partial nephrectomy (PN) for the detection of renal artery pseudoaneurysm (PA) and to allow pre-emptive arterial embolization to reduce the postoperative bleeding risk. MATERIALS AND METHODS: A retrospective study was conducted including all consecutive patients treated with robot-assisted PN for renal tumours between 2015 and 2017. Every patient underwent renal DUS in the early postoperative period. The presence of PA, arteriovenous malformation or collection on the DUS, as well as the incidence of haemorrhagic complications and need for transfusion/embolization were assessed. RESULTS: Eighty-three patients were included, with a median (range) age of 58 (19-80) years. The median (range) follow-up was 5 (1-30) months. The mean (±sd) tumour size was 31 (±13.1) mm, the median (range) RENAL nephrometry score was 6 (4-11), and the mean (±sd) warm ischaemia time was 22 (±7) min. A haemostatic agent was used in 12 patients (14.5%). No patient encountered haemorrhagic complications postoperatively, and no patient required transfusion. The median (interquartile range) time to DUS postoperatively was 7 (6-8) days. DUS revealed one asymptomatic PA (1.2%), which was treated with pre-emptive embolization. This was the only patient who encountered a Clavien grade III complication, while 20 patients (24%) had a complication grade I/II. CONCLUSIONS: No haemorrhagic complications occurred in the present study population, although one asymptomatic PA was found. It was diagnosed early with DUS, allowing pre-emptive management with embolization. These results suggest the potential clinical utility of early postoperative DUS in order to screen for PA to reduce the risk of post-PN haemorrhagic complications.

Postprostatectomy incontinence is related to pelvic floor displacements observed with trans-perineal ultrasound imaging.

AIMS: To investigate the relationship between post-prostatectomy incontinence and dynamic features of activation of specific pelvic floor muscles in addition to anatomical parameters of the urethra. METHODS: Forty-two men aged 66 (7) years (incontinent [N = 19] and continent [N = 23]) who had undergone prostatectomy participated. Transperineal ultrasound imaging was used to record sagittal images of pelvic structures during involuntary coughing and sustained maximal voluntary contractions. Imaging data were analyzed to calculate displacements of pelvic floor landmarks associated with activation of the puborectalis, striated urethral sphincter, and bulbocavernosus muscles. Anatomical features of functional urethral length and the resting position of the ano-rectal and urethra-vesical junctions were calculated. A principal component analysis and multiple logistic regression were used to consider which combinations of variables best distinguish between men with and without incontinence. RESULTS: Five principal components were identified that together explained 72.0% of the data. Two principal components that represented (i) striated urethral sphincter activation and (ii) bulbocavernosus and puborectalis muscle activation were significantly different between participants with and without incontinence. Together these components correctly identified 88.1% of incontinent men, with a specificity and sensitivity of 91.3% and 84.2%, respectively. Poor function of the bulbocavernosus and puborectalis muscles could be compensated by good striated urethral sphincter function, but the bulbocavernosus and puborectalis muscles had less potential to compensate for poor striated urethral sphincter function. CONCLUSIONS: Dynamic features of pelvic floor muscle activation, particularly shortening of the striated urethral sphincter during cough and voluntary contraction, are related to continence status after prostatectomy.

Initial multicentre experience of 68 gallium-PSMA PET/CT guided robot-assisted salvage lymphadenectomy: acceptable safety profile but oncological benefit appears limited.

OBJECTIVES: To evaluate the safety and short-term oncological outcomes of 68 gallium-labelled prostate-specific membrane antigen (68 Ga-PSMA) positron-emission tomography (PET)/computed tomography (CT)-directed robot-assisted salvage node dissection (RASND) for prostate cancer oligometastatic nodal recurrence. MATERIALS AND METHODS: Between February 2014 and April 2016, 35 patients across two centres underwent RASND for 68 Ga-PSMA PET/CT-detected oligometastatic nodal recurrence. RASND was performed using targeted pelvic dissection, unilateral extended pelvic template or bilateral extended pelvic template dissection, depending on previous pelvic treatment and extent/location of nodal disease. Complications were reported using the Clavien-Dindo classification system. Definitions of prostate-specific antigen (PSA) treatment response to RASND were defined as 6-week PSA <0.2 ng/mL (broad definition) or PSA <0.05 ng/mL (strict definition) in those who had undergone primary prostatectomy, and 6-week PSA level < post-radiotherapy nadir in those who had undergone primary radiotherapy. Biochemical recurrence (BCR) after RASND was defined as a PSA >0.2 ng/mL or PSA > nadir, for those who had undergone primary prostatectomy and primary radiotherapy, respectively. Predictors of treatment response were analysed using univariate binary logistic regression. RESULTS: A total of 58 lesions suspicious for lymph node metastases (LNM) in 35 patients were detected on 68 Ga-PSMA imaging. A total of 32 patients (91%) had histopathologically proven LNM at RASND, with a total of 87 LNM and a median (interquartile range) of 2 (1-3) LNM per patient. In all, eight patients (23%) experienced complications, all Clavien-Dindo grade ≤2. Treatment response was seen in 15 (43%) and 11 patients (31%), using the broad and strict definitions, respectively. BCR-free survival and clinical recurrence-free survival at a median follow-up of 12 months were 23% and 66%, respectively, for the entire cohort. Bilateral template dissection was the only significant univariate predictor of treatment response in our cohort. CONCLUSIONS: Although RASND appears safe and feasible, less than half of our cohort had a treatment response, and less than a quarter experienced BCR-free survival at 12-month median follow-up. 68 Ga-PSMA imaging underestimates micro-metastatic disease, therefore RASND will rarely be curative. Strict patient selection and restricting RASND to clinical trials is recommended. Long-term follow-up from such trials is required to further assess potential quality of life and mortality benefits.

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

INTRODUCTION: 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. METHODS: This retrospective single tertiary referral institution cohort study of men reviewed the results of 68  Ga-PSMA PET/CT scans for investigation of post RP and post radiotherapy PSA recurrence following primary treatment of prostate cancer. We included men with suspected recurrent prostate cancer based on an elevated post treatment PSA level. The data collected analyzed the relationship of the pre-scan PSA level to the probability of a positive scan finding for recurrent prostate cancer. RESULTS: Of the cohort of 532 men, 425 had a previous RP and 107 had prior radiotherapy. The median PSA of the RP group was 0.59 ng/mL and 5.8 ng/mL in the radiotherapy group. In the post RP cohort, the detection rate of 68  Ga-PSMA PET/CT was 11.3% for PSA 0.01 to <0.2 ng/mL, 26.6% for PSA 0.2 to <0.5 ng/mL, 53.3% for PSA 0.5 to <1 ng/mL, 79.1% for PSA 1 to <2 ng/mL and 95.5% for PSA ≥2. Lymph node metastasis post RP was identified in 68% of men with suspected disease recurrence. In the post radiotherapy cohort the detection rate was 33.3% for PSA 0.01 to <0.5 ng/mL, 71.4% for PSA 0.5 to <1 ng/mL, 93.3% for PSA 1 to <2 ng/mL and 100% for PSA ≥2. Local recurrence after radiotherapy was suspected in 71% of the cohort and 40% had suspected lymph node metastasis. CONCLUSIONS: To our knowledge, this is largest cohort study of detection rates of 68  Ga-PSMA PET/CT in patients with biochemical recurrence after definitive treatment of prostate cancer, including patients with PSA <0.5 and in a post radiotherapy cohort. Detection of suspected recurrent disease outside the pelvis at low PSA levels will influence the decision for salvage treatment options.

Pattern of activation of pelvic floor muscles in men differs with verbal instructions.

AIMS: To investigate the effect of instruction on activation of pelvic floor muscles (PFM) in men as quantified by transperineal ultrasound imaging (US) and to validate these measures with invasive EMG recordings. METHODS: Displacement of pelvic floor landmarks on transperineal US, intra-abdominal pressure (IAP) recorded with a nasogastric transducer, and surface EMG of the abdominal muscles and anal sphincter were recorded in 15 healthy men during sub-maximal PFM contractions in response to different verbal instructions: "tighten around the anus," "elevate the bladder," "shorten the penis," and "stop the flow of urine." In three men, fine-wire EMG recordings were made from puborectalis and bulbocavernosus, and trans-urethral EMG recordings from the striated urethral sphincter (SUS). Displacement data were validated by analysis of relationship with invasive EMG. Displacement, IAP, and abdominal/anal EMG were compared between instructions. RESULTS: Displacement of pelvic landmarks correlated with the EMG of the muscles predicted anatomically to affect their locations. Greatest dorsal displacement of the mid-urethra and SUS activity was achieved with the instruction "shorten the penis." Instruction to "elevate the bladder" induced the greatest increase in abdominal EMG and IAP. "Tighten around the anus" induced greatest anal sphincter activity. CONCLUSIONS: The pattern of urethral movement measured from transperineal US is influenced by the instructions used to teach activation of the pelvic floor muscles in men. Efficacy of PFM training may depend on the instructions used to train activation. Instructions that optimize activation of muscles with a potential to increase urethral pressure without increasing abdominal EMG/IAP are likely ideal. Neurourol. Urodynam. 35:457-463, 2016. © 2015 Wiley Periodicals, Inc.

The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology: A single centre retrospective study.

Objective: To review the risk of prostate cancer (PCa) in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) ordered at Department of Urology, The Wesley Hospital, Brisbane, QLD, Australia for non-PCa related pathology. Methods: Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted. Men were classified as benign, indeterminate, or malignant depending of the results of prostate-specific antigen (PSA), PSA velocity, biopsy histopathology, and three-Tesla (3 T) multiparametric MRI (mpMRI) Prostate Imaging Reporting and Data System score, or gallium-68-prostate-specific membrane antigen (68Ga-PSMA) PET/CT results. Results: Three percent (273/9122) of men demonstrated 18F-FDG avidity within the prostate. Eighty-five percent (231/273) were further investigated, including with PSA tests (227/231, 98.3%), 3 T mpMRI (68/231, 29.4%), 68Ga-PSMA PET/CT (33/231, 14.3%), and prostate biopsy (57/231, 24.7%). Results were considered benign in 130/231 (56.3%), indeterminate in 31/231 (13.4%), and malignant in 70/231 (30.3%). PCa was identified in 51/57 (89.5%) of the men who proceeded to biopsy, including 26/27 (96.3%) men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/CT. The most common Gleason score on biopsy was greater than or equal to 4+5 (14/51, 27.5%). 68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33 (78.8%). All 13 men with a positive concordant 18F-FDG, 3 T mpMRI, and 68Ga-PSMA PET/CT had PCa on biopsy. There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups (5.7 vs. 6.1; p=0.580). Conclusion: In this study, after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT, 70 of the 231 cases (30.3%; 0.8% of the entire cohort) had results consistent with PCa, most commonly as Gleason score greater than or equal to 4+5 disease. Unless there is limited life expectancy due to competing medical co-morbidity, men with an incidental finding of intraprostatic uptake on 18F-FDG should be further investigated using principles of PCa detection.

Reproducibility and Accuracy of the PRIMARY Score on PSMA PET and of PI-RADS on Multiparametric MRI for Prostate Cancer Diagnosis Within a Real-World Database.

The PRIMARY score is a 5-category scale developed to identify clinically significant intraprostate malignancy (csPCa) on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT (68Ga-PSMA PET) using a combination of anatomic site, pattern, and intensity. Developed within the PRIMARY trial, the score requires evaluation in external datasets. This study aimed to assess the reproducibility and diagnostic accuracy of the PRIMARY score in a cohort of patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET before prostate biopsy for the diagnosis of prostate cancer. Methods: In total, data from 242 men who had undergone 68Ga-PSMA PET and mpMRI before transperineal prostate biopsy were available for this ethics-approved retrospective study. 68Ga-PSMA PET and mpMRI data were centrally collated in a cloud-based deidentified image database. Six experienced prostate-focused nuclear medicine specialists were trained (1 h) in applying the PRIMARY score with 30 sample images. Six radiologists experienced in prostate mpMRI read images as per the Prostate Imaging-Reporting and Data System (PI-RADS), version 2.1. All images were read (with masking of clinical information) at least twice, with discordant findings sent to a masked third (or fourth) reader as necessary. Cohen κ was determined for both imaging scales as 5 categories and then collapsed to binary (negative and positive) categories (score 1 or 2 vs. 3, 4, or 5). Diagnostic performance parameters were calculated, with an International Society of Urological Pathology grade group of at least 2 (csPCa) on biopsy defined as the gold standard. Combined-imaging-positive results were defined as any PI-RADS score of 4 or 5 or as a PI-RADS score of 1-3 with a PRIMARY score of 3-5. Results: In total, 227 patients with histopathology, 68Ga-PSMA PET, and mpMRI imaging before prostate biopsy were included; 33% had no csPCa, and 67% had csPCa. Overall interrater reliability was higher for the PRIMARY scale (κ = 0.70) than for PI-RADS (κ = 0.58) when assessed as a binary category (benign vs. malignant). This was similar for all 5 categories (κ = 0.65 vs. 0.48). Diagnostic performance to detect csPCa was comparable between PSMA PET and mpMRI (sensitivity, 86% vs. 89%; specificity, 76% vs. 74%; positive predictive value, 88% vs. 88%; negative predictive value, 72% vs. 76%). Using combined imaging, sensitivity was 94%, specificity was 68%, positive predictive value was 86%, and negative predictive value was 85%. Conclusion: The PRIMARY score applied by first-user nuclear medicine specialists showed substantial interrater reproducibility, exceeding that of PI-RADS applied by mpMRI-experienced radiologists. Diagnostic performance was similar between the 2 modalities. The PRIMARY score should be considered when interpreting intraprostatic PSMA PET images.