High adherence to Western dietary pattern and prostate cancer risk: findings from the EPIC-Spain cohort.

OBJECTIVE: To explore the association between three previously identified dietary patterns (Western, Prudent and Mediterranean) and prostate cancer (PCa) risk by tumour aggressiveness. SUBJECTS AND METHODS: The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided dietary and epidemiological information from 15 296 men recruited during the period 1992-1996. The associations between the adherence to the three dietary patterns and PCa risk (global, for Gleason grade groups 6 and >6, and for International Society of Urological Pathology [ISUP] grade 1 + 2 and ISUP grade 3 + 4 + 5) was explored with multivariable Cox proportional hazards regression models stratified by centre and age. RESULTS: While no effect on PCa risk was detected for the Prudent and Mediterranean dietary patterns, a suggestion of a detrimental effect of the Western dietary pattern was found (hazard ratio [HR]Q4vsQ1 1.29 [95% confidence interval {CI} 0.96;1.72]). This effect was only observed for Gleason grade group >6 (HRQ3vsQ1 1.61 [95% CI 1.00; 2.59] and HRQ4vsQ1 1.60 [95% CI 0.96; 2.67]) and in particular ISUP grade 3 + 4 + 5 tumours (HRQ2vsQ1 1.97 [95% CI 0.98; 3.93]; HRQ3vsQ1 2.72 (95% CI 1.35; 5.51); HRQ4vsQ1 2.29 [95% CI 1.07; 4.92]). CONCLUSIONS: Our results suggest that a high adherence to a healthy diet such as that represented by the Prudent and Mediterranean dietary patterns is not enough to prevent prostate cancer. Additionally, reducing adherence to a Western-type diet seems to be necessary.

Same-day discharge robot-assisted laparoscopic prostatectomy: feasibility, safety and patient experience.

OBJECTIVES: To report a single centre's experience of the feasibility, safety and patient acceptability of same-day discharge robot-assisted laparoscopic prostatectomy (RALP). SUBJECTS/PATIENTS AND METHODS: Between June 2015 and December 2021, a total of 180 pre-selected consecutive patients underwent RALP with the intention to discharge on the same day as surgery. Cases were performed by two surgeons. An enhanced recovery after surgery (ERAS) programme was used. The feasibility of same-day discharge was analysed, along with the complication rate, oncological outcomes, and postoperative patient experience. RESULTS: Of 180 patients, 169 (93.8%) were successfully discharged on the same day as surgery. The median (range) age was 63 ( 44-74) years. The median (range) console time was 97 (61-256) min and blood loss was 200 (20-800) mL. The resection specimen pathology results were: pT2 69.4%, pT3a 24.4% and pT3b 6.5%. With regard to Gleason Grade Group (GGG), 25.9% had GGG 1, 65.7% had GGG 2-3 and 8.4% had GGG 4-5 disease. Positive surgical margins were present in 25 cases (14.7%), 18 (15.5%) of which occurred in pT2 cases, and seven (13.4%) in pT3 cases. There were no early (<90 days) biochemical relapses (defined as prostate-specific antigen level >0.2 ng/mL). The 30-day readmission rate was 3%. A total of 13 early (0-30 days) complications were observed, five of which were Clavien-Dindo grade ≥3, however, none of these would have been avoided had the patient remained in hospital on the first postoperative night. Of 121 consecutive patients, 107 (88%) returned a satisfaction questionnaire, and 92% of responders stated they preferred recovery at home, with 94% stating they felt ready to go home. CONCLUSION: Robot-assisted laparoscopic prostatectomy combined with an ERAS programme allows patients to be safely discharged home on the same day of their surgery. This is a feasible option, well-liked by patients, with morbidity and oncological outcomes similar to non-day-case or 23 h stay RALP.

Validation of the prognostic value of a three-gene signature and clinical parameters-based risk score in prostate cancer patients.

BACKGROUND: The study aimed to validate the prognostic value of the Prostatype® risk score (P-score), which includes a three-gene signature and conventional risk factors, in a retrospective cohort. METHODS: All 716 patients diagnosed with prostate cancer from 2008 to 2010 at Skåne University Hospital, Sweden, were included. After excluding patients based on pathological and clinical eligibility criteria, RNA quality, and presence of metastases at diagnosis, a final cohort comprising 316 patients was further analyzed. Expression levels of three genes (IGFBP3, F3, and VGLL3) were measured in archived formalin-fixed paraffin-embedded core needle biopsies. The gene expression data were combined with clinical parameters (Gleason score, prostate-specific antigen, and clinical tumor stage) to calculate the P-score for each patient. Predictive performance of the P-score in terms of prostate cancer-specific mortality (PCSM), distant metastasis and adverse pathological outcomes were investigated. RESULTS: The P-score predicted both PCSM (hazard ratio [HR] = 1.6) and metastasis (HR = 1.46). The P-score had an area under curve (AUC) of 0.93 when predicting the PCSM risk at 10 years (95% confidence interval [CI]: 0.89-0.98), which was significantly better than both D'Amico (AUC: 0.81, 95% CI: 0.72-0.90, p < 0.001) and UCSF-CAPRA (AUC: 0.88, 95% CI: 0.80-0.96, p < 0.05). Decision curve analysis showed a higher net benefit of the P-score compared to both D'Amico and CAPRA. All three risk scores performed similarly in the prediction of distant metastases. For patients who underwent radical prostatectomy (RP), a higher P-score correlated with adverse pathological features such as pathologic tumor stage T3-4 (p < 0.0001) and ≥International Society of Urological Pathology grade group 3 (p < 0.0001). CONCLUSIONS: Our findings provide evidence for the prognostic value of the P-score. The P-score predicted the risk for PCSM more accurately than the D'Amico and CAPRA scores. Performance was similar when predicting the risk for development of distant metastases within 10 years. Moreover, the P-score correlated with adverse pathological outcomes in RP specimens. Thus, the P-score could provide useful information for patients and their doctors to make informed decisions at the time of diagnosis.

Standardized prostate cancer incidence and mortality rates following initial non-malignant biopsy result.

OBJECTIVES: To compare the incidence of subsequent prostate cancer diagnosis and death following an initial non-malignant systematic transrectal ultrasonography (TRUS) biopsy with that in an age- and calendar-year matched population over a 20-year period. SUBJECTS AND METHODS: This population-based analysis compared a cohort of all men with initial non-malignant TRUS biopsy in Denmark between 1995 and 2016 (N = 37 231) with the Danish population matched by age and calendar year, obtained from the NORDCAN 9.1 database. Age- and calendar year-corrected standardized prostate cancer incidence (SIR) and prostate cancer-specific mortality ratios (SMRs) were calculated and heterogeneity among age groups was assessed with the Cochran's Q test. RESULTS: The median time to censoring was 11 years, and 4434 men were followed for more than 15 years. The corrected SIR was 5.2 (95% confidence interval [CI] 5.1-5.4) and the corrected SMR was 0.74 (95% CI 0.67-0.81). Estimates differed among age groups (P < 0.001 for both), with a higher SIR and SMR among younger men. CONCLUSION: Men with non-malignant TRUS biopsy have a much higher incidence of prostate cancer but a risk of prostate cancer death below the population average. This underlines that the oncological risk of cancers missed in the initial TRUS biopsy is low. Accordingly, attempts to increase the sensitivity of initial biopsy are unjustified. Moreover, current follow-up after non-malignant biopsy is likely to be overaggressive, particularly in men over the age of 60 years.

Protocol for the TRANSLATE prospective, multicentre, randomised clinical trial of prostate biopsy technique.

OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.

Exercise training to increase tumour natural killer-cell infiltration in men with localised prostate cancer: a randomised controlled trial.

OBJECTIVES: To explore the effects of preoperative high-intensity interval training (HIIT) compared to usual care on tumour natural killer (NK)-cell infiltration in men with localised prostate cancer (PCa), as NK-cell infiltration has been proposed as one of the key mechanisms whereby exercise can modulate human tumours. PATIENTS AND METHODS: A total of 30 patients with localised PCa undergoing radical prostatectomy (RP) were randomised (2:1) to either preoperative aerobic HIIT four-times weekly (EX; n = 20) or usual care (CON; n = 10) from time of inclusion until scheduled surgery. Tumour NK-cell infiltration was assessed by immunohistochemistry (CD56+ ) in diagnostic core needle biopsies and corresponding prostatic tissue from the RP. Changes in cardiorespiratory fitness, body composition, blood biochemistry, and health-related quality of life were also evaluated. RESULTS: The change in tumour NK-cell infiltration did not differ between the EX and CON groups (between-group difference: -0.09 cells/mm2 , 95% confidence interval [CI] -1.85 to 1.66; P = 0.913) in the intention-to-treat analysis. The total number of exercise sessions varied considerably from four to 30 sessions. The per-protocol analysis showed a significant increase in tumour NK-cell infiltration of 1.60 cells/mm2 (95% CI 0.59 to 2.62; P = 0.004) in the EX group. Further, the total number of training sessions was positively correlated with the change in NK-cell infiltration (r = 0.526, P = 0.021), peak oxygen uptake (r = 0.514, P = 0.035) and peak power output (r = 0.506, P = 0.038). CONCLUSION: Preoperative HIIT did not result in between-group differences in tumour NK-cell infiltration. Per-protocol and exploratory analyses demonstrate an enhanced NK-cell infiltration in PCa. Future studies are needed to test the capability of exercise to increase tumour immune cell infiltration.

Phase II proof-of-concept study of atorvastatin in castration-resistant prostate cancer.

OBJECTIVES: To test for evidence of statin-mediated effects in patients with castration-resistant prostate cancer (CRPC) as post-diagnosis use of statins in patients with prostate cancer is associated with favourable survival outcome. PATIENTS AND METHODS: The SPECTRE trial was a 6-weeks-long proof-of-concept single-arm Phase II treatment trial, combining atorvastatin and androgen deprivation therapy in patients with CRPC (regardless of metastatic status), designed to test for evidence of statin-mediated effects in patients with CRPC. The primary study endpoint was the proportion of patients achieving a ≥50% drop from baseline in prostate-specific antigen (PSA) levels at any time over the 6-week period of atorvastatin medication (PSA response). Exploratory endpoints include PSA velocity and serum metabolites identified by mass spectrometry . RESULTS: At the scheduled interim analysis, one of 12 patients experienced a ≥50% drop in PSA levels (primary endpoint), with ≥2 patients satisfying the primary endpoint required for further recruitment. All 12 patients experienced substantial falls in serum cholesterol levels following statin treatment. While all patients had comparable pre-study PSA velocities, six of 12 patients showed decreased PSA velocities after statin treatment, suggestive of disease stabilization. Unbiased metabolomics analysis on serial weekly blood samples identified tryptophan to be the dominant metabolite associated with patient response to statin. CONCLUSIONS: Data from the SPECTRE study provide the first evidence of statin-mediated effects on CRPC and early sign of disease stabilization. Our data also highlight the possibility of altered tryptophan metabolism being associated with tumour response.

Impact of centralization of prostate cancer services on the choice of radical treatment.

OBJECTIVE: To assess the impact of centralization of prostate cancer surgery and radiotherapy services on the choice of prostate cancer treatment. PATIENTS AND METHODS: This national population-based study used linked cancer registry data and administrative hospital-level data for all 16 621 patients who were diagnosed between 1 January 2017 and 31 December 2018 with intermediate-risk prostate cancer and who underwent radical prostatectomy (RP) or radical radiation therapy (RT) in the English National Health Service (NHS). Travel times by car to treating centres were estimated using a geographic information system. We used logistic regression to assess the impact of the relative proximity of alternative treatment options on the type of treatment received, with adjustment for patient characteristics. RESULTS: Of the 78 NHS hospitals that provide RT or RP for prostate cancer, 41% provide both, 36% provide RT and 23% provide RP. Compared to patients who had both treatment options available at their nearest centre where overall 57% of patients received RT and 43% RP, patients were less likely to receive RT if their nearest centre offered RP only and the extra travel time to a hospital providing RT was >15 min (52% of patients received RT and 48% RP%, odds ratio [OR] 0.70 (0.58-0.85); P < 0.001). Conversely, patients were more likely to receive RT if their nearest centre offered RT and the extra travel time to a hospital providing RP was >15 min (63% of patients received RT and 37% RP, OR 1.23 (1.08-1.40); P < 0.001). There was a negligible impact on the type of treatment received if centres providing alternative treatment options were ≤15-min travel time from each other. CONCLUSION: The relative proximity of prostate cancer treatment options to a patient's residence is an independent predictor for the type of radical treatment received. Centralization policies for prostate cancer should not focus on one treatment modality but should consider all treatments to avoid a negative impact on treatment choice.

A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

Evidence of cancer progression as the cause of death in men with prostate cancer in Sweden.

OBJECTIVE: To assess the strength of the evidence indicative of prostate cancer (PCa) progression as the adjudicated cause of death, according to age at death and PCa risk category. PATIENTS AND METHODS: Using data from the Prostate Cancer data Base Sweden, we identified a study frame of 5543 men with PCa registered as the cause of death according to the Cause of Death Register. We assessed the evidence of PCa progression through a review of healthcare records for a stratified sample of 495/5543. We extracted data on prostate-specific antigen levels, presence of metastases on imaging, and PCa treatments, and quantified the evidence of disease progression using a points system. RESULTS: Both no evidence and moderate evidence for PCa progression was more common in men aged >85 years at death than those aged <85 years (29% vs 14%). Among the latter, the proportion with no evidence or moderate evidence for PCa progression was 21% for low-risk, 14% for intermediate-risk, 8% for high-risk, and 0% for metastatic PCa. In contrast, in men aged >85 years, there was little difference in the proportion with no evidence or moderate evidence of PCa progression between PCa risk categories; 31% for low-risk, 29% for intermediate-risk, 29% for high-risk, and 21% for metastatic PCa. Of the 5543 men who died from PCa, 13% (95% confidence interval 5-19%) were estimated to have either no evidence or moderate evidence of PCa progression. CONCLUSIONS: Weak evidence for PCa progression as cause of death was more common in older men with PCa and in those with low-risk PCa. This has implications for interpretation of mortality statistics especially when assessing screening and early treatment of PCa because the beneficial effect of earlier diagnosis could be masked by erroneous adjudication of PCa as cause of death in older men, particular those with localised disease at diagnosis.

Treatment decision regret in long-term survivors after radical prostatectomy: a longitudinal study.

OBJECTIVES: To investigate prevalence, course, and predictors of longitudinal decision regret in long-term prostate cancer (PCa) survivors treated by radical prostatectomy (RP). PATIENTS AND METHODS: A total of 1003 PCa survivors from the multicentre German Familial PCa Database completed questionnaires on average 7 years after RP in 2007 and at follow-up 13 years later in 2020. Patients completed standardised patient-reported outcome measures on decision regret, decision-making, health-related quality of life, and psychosocial factors. Hierarchical multivariable logistic regression was used to assess predictors of longitudinal decision regret. RESULTS: Decision regret increased significantly over time (9.0% after 6.9 years in 2007 and 12% after 19 years in 2020; P = 0.009). Favourable localised PCa (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.05-3.68), decision regret in 2007 (OR 6.38, 95% CI 3.55-11.47), and a higher depression score (OR 1.37, 95% CI 1.03-1.83) were associated with decision regret in 2020. Shared decision-making (OR 0.55, 95% CI 0.33-0.93) was associated with less decision regret. CONCLUSION: The findings of the present study underline the perseverance of decision regret in long-term PCa survivors and the definitive need for involving patients in the decision-making process to mitigate regret over the long term.

Sustainable functional urethral reconstruction improves early urinary continence after robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To evaluate the impact of sustainable functional urethral reconstruction (SFUR) on early recovery of urinary continence (UC) after robot-assisted radical prostatectomy. PATIENTS AND METHODS: Overall, 96 patients with primary prostate cancer were randomised into the SFUR or standard group (n = 48 each). The primary outcome was the 1-month UC recovery. Secondary outcomes included short-term (≤3 months) UC recovery, urinary function, micturition-related bother, perioperative complications, and oncological outcomes. Kaplan-Meier curves and Cox proportional hazard models were used to assess the 3-month UC recovery. Generalised estimating equations were used to compare postoperative urinary function and micturition-related bother. RESULTS: The 1-month UC recovery rates, median 24-h pad weights, and median operative time in the SFUR and standard groups were 73% and 49% (P = 0.017), 0 and 47 g (P = 0.001), and 125 and 103 min (P = 0.025), respectively. The UC recovery rates in the SFUR vs standard groups were 53% vs 23% at 1 week (P = 0.003), 53% vs 32% at 2 weeks (P = 0.038), and 93% vs 77% at 3 months (P = 0.025). The median time to UC recovery in the SFUR and standard groups was 5 and 34 days, respectively (log-rank P = 0.006); multivariable Cox regression supported this result (hazard ratio 1.73, 95% confidence interval 1.08-2.79, P = 0.024). Similar results were observed when UC was defined as 0 pads/day. Urinary function (P = 0.2) and micturition-related bother (P = 0.8) were similar at all follow-up intervals. The perioperative complication rates, positive surgical margin rates, and 1-year biochemical recurrence-free survival were comparable between both groups (all P > 0.05). CONCLUSION: SFUR resulted in earlier UC recovery without compromising postoperative urinary function. Long-term validation and multicentre studies are required to confirm the results of this novel technique.

Median 5-year outcomes of primary focal irreversible electroporation for localised prostate cancer.

OBJECTIVES: To evaluate longer-term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at a median follow-up of 5 years (up to 10 years). PATIENTS AND METHODS: All patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow-up were analysed. Follow-up included 6-month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate-specific antigen (PSA) levels. Failure-free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy. RESULTS: A total of 229 patients were analysed with a median (interquartile range [IQR]) follow-up of 60 (40-80) months. The median (IQR) age was 68 (64-74) years, the median (IQR) PSA level was 5.9 (4.1-8.2) ng/mL, and 86% harboured intermediate-risk disease and 7% high-risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17-53) months after IRE. Kaplan-Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis-free survival was 99.6% (228/229), PCa-specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow-up biopsy and MRI showed a complete ablation in 82% (186/226). Short-term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%). CONCLUSION: Longer-term follow-up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long-term follow-up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.

Confocal laser microscopy for assessment of surgical margins during radical prostatectomy.

OBJECTIVE: To evaluate the feasibility of confocal laser microscopy (CLM) for intraoperative margin assessment as faster alternative to neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Surgical margins were assessed during 50 RARP procedures in patients scheduled for NeuroSAFE. Posterolateral sections were cut and imaged with CLM and further processed to conform with the NeuroSAFE protocol. Secondary resection (SR) was performed in case a positive surgical margin (PSM) was observed with NeuroSAFE. Afterwards, the CLM images were non-blinded assessed for the presence of PSMs. The accuracy of both NeuroSAFE and CLM was compared with conventional histopathology. Agreement for detection of PSMs between NeuroSAFE and CLM was evaluated with Cohen's kappa coefficient. Procedure times were compared with a Wilcoxon signed-ranks test. RESULTS: In total, 96 posterolateral sections of RP specimens were evaluated for the presence of PSMs. CLM identified 15 (16%) PSMs and NeuroSAFE identified 14 (15%) PSMs. CLM had a calculated sensitivity, specificity, positive predictive value and negative predictive value of 86%, 96%, 80% and 98% respectively for the detection of PSMs compared to definite pathology. After SR, residual tumour was found in six of 13 cases (46%), which were all identified by both techniques. There was a substantial level of agreement between CLM and NeuroSAFE (κ = 0.80). The median procedure time for CLM was significantly shorter compared to NeuroSAFE (8 vs 50 min, P < 0.001). The main limitation of this study was the non-blinded assessment of the CLM images. CONCLUSIONS: Compared to NeuroSAFE, CLM is a promising technique for intraoperative margin assessment and is able to reduce the time of intraoperative margin assessment.

Prevalence of prostate cancer in men with haematuria: a systematic review and meta-analysis.

OBJECTIVES: To investigate the prevalence of prostate cancer in men attending evaluation for haematuria, as this could help healthcare providers to determine whether men with haematuria should have prostate examinations performed. METHODS: The study was performed according to a pre-specified protocol uploaded to the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022299383). A systematic search of MEDLINE, Ovid and Google Scholar was performed in December 2021. Two independent researchers evaluated all titles, available abstracts, and full texts. We included studies on adult men (aged ≥18 years) describing haematuria and prostate cancer. RESULTS: We screened 4252 titles and abstracts when available and assessed 350 studies in full text. In total, 65 studies were included and 42 was summarised in a meta-analysis. In total, 18 752 men with haematuria were included, and the pooled prevalence (95% confidence interval [CI]) of prostate cancer was 3.0% (2.0-4.1%). In men with macroscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 5.9% (2.9-9.9%; n = 265/5373). In men with microscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 1.4% (0.8-2.2%; n = 71/6642). CONCLUSION: Our findings indicate that the prevalence of prostate cancer is considerable in men attending evaluation for haematuria. Therefore, digital rectal examination and prostate-specific antigen measurement should become a standard procedure for all men with haematuria, especially for men with macroscopic haematuria.

Shifting risk-stratified early prostate cancer detection to a primary healthcare setting.

OBJECTIVE: To evaluate the feasibility of multivariable risk stratification for early prostate cancer (PCa) detection in a primary healthcare diagnostic facility with regard to its effects on the referral rate and subsequent PCa diagnoses compared to a PSA threshold of 3.0 ng/mL as the current referral indicator. PATIENTS AND METHODS: In 2014, the Erasmus MC Cancer Institute and the primary healthcare diagnostic facility STAR-SHL (located in Rotterdam city centre) initiated this observational study, in which general practitioners (GPs) could refer men who wished to undergo PCa screening to STAR-SHL for consultation by specially trained personnel. Referral recommendations to secondary healthcare were based on the outcome of application of the Rotterdam Prostate Cancer Risk Calculator (RPCRC) and were compared to the current Dutch GPs' PSA referral threshold of 3.0 ng/mL. For data collection on PCa diagnoses, the study cohort was linked to the Dutch nationwide pathology databank (PALGA). RESULTS: Between January 2014 and February 2021, 507 men were referred for consultation and in 495 men prostate-specific antigen (PSA) was tested. The median (interquartile range) follow-up from consultation to PALGA linkage was 43 (25-65) months. In total, 279 men (56%) had a PSA level ≥3.0 ng/mL, of whom 68% (95% confidence interval [95% CI] 63-74) were considered at low risk according to the RPCRC. Within 1 year after consultation, one of these men (0.52%; 95% CI 0.092-2.9) was diagnosed with clinically significant (cs)PCa (i.e., International Society of Urological Pathology Grade Group ≥2). Thereafter, another four (2.1%; 95% CI 0.82-5.3) low-risk men were diagnosed with csPCa. Of the high-risk men who were biopsied within 1 year after consultation (n = 61), 77% (95% CI 65-86) were diagnosed with PCa and 49% (95% CI 37-61) with csPCa. CONCLUSION: In a primary healthcare diagnostic facility, the RPCRC could reduce up to 68% of referrals to secondary healthcare, as compared to a PSA referral threshold of 3.0 ng/mL. Deploying the RPCRC in this setting resulted in a high csPCa detection rate in those men biopsied. This strategy can be considered safe since the observational data showed low proportions of csPCa among men at low risk.

The prognostic value of lymph node staging with prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and extended pelvic lymph node dissection in node-positive patients with prostate cancer.

OBJECTIVES: To investigate whether patients with suspected pelvic lymph node metastases (molecular imaging [mi] N1) on staging prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) had a different oncological outcome compared to those in whom the PSMA PET/CT did not reveal any pelvic lymph node metastases (miN0). PATIENTS AND METHODS: All patients with pelvic lymph node metastatic (pN1) disease after robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) between January 2017 and December 2020 were included. To assess predictors of biochemical progression of disease after RARP, a multivariable Cox regression analysis was performed, including number of tumour-positive lymph nodes, diameter of the largest nodal metastasis, and extranodal extension. RESULTS: In total, 145 patients were diagnosed with pN1 disease after ePLND. The median biochemical progression-free survival in patients with miN0 on PSMA PET/CT was 13.7 months, compared to 7.9 months in patients with miN1 disease (P = 0.006). On multivariable Cox regression analysis, both number of tumour-positive lymph nodes (>2 vs 1-2: hazard ratio [HR] 1.97; P = 0.005) and diameter of the largest nodal metastasis (HR 1.12; P < 0.001) were significant independent predictors of biochemical progression of disease. CONCLUSION: Patients in whom pelvic lymph node metastases were suspected on preoperative PSMA imaging (miN1), patients diagnosed with >2 tumour-positive lymph nodes, and patients with a larger diameter of the largest nodal metastasis had a significantly increased risk of biochemical disease progression after surgery.

Synchronous vs independent reading of prostate-specific membrane antigen positron emission tomography (PSMA-PET) and magnetic resonance imaging (MRI) to improve diagnosis of prostate cancer.

OBJECTIVES: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68 Ga-PSMA-11 positron emission tomography (PET)/computed tomography (prostate-specific membrane antigen [PSMA-PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA-PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. METHODS: This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual-trained radiologist/nuclear medicine physicians re-reported the mpMRI and PSMA-PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA-PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. 'Concordance' between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the individual reporters for each modality. RESULTS: International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA-PET increased sensitivity compared to mpMRI or PSMA-PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA-PET read synchronously and mpMRI or PSMA-PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions; 12%). When mpMRI/PSMA-PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA-PET alone was compared to synchronous PSMA-PET/MRI reads, there was an improvement in reader certainty in 20% of scans. CONCLUSION: Synchronous mpMRI/PSMA-PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA-PET alone. However, synthesizing the results of independently read PSMA-PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA-PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis.

A systematic review on the outcomes of local anaesthetic transperineal prostate biopsy.

OBJECTIVE: To conduct a systematic review of the literature to assess the diagnostic ability, complication rate, patient tolerability, and cost of local anaesthetic (LA) transperineal prostate biopsy. METHODS: Two reviewers searched Medline, the Cochrane Library, and Embase for publications on LA transperineal prostate biopsy up to March 2021. Outcomes of interest included cancer detection rates, complication rates, pain assessments and cost. RESULTS: A total of 35 publications with 113 944 men were included in this review. The cancer detection rate for LA transperineal prostate biopsy in patients undergoing primary biopsy was 52% (95% confidence interval [CI] 0.45-0.60; I2 = 97) and the clinically significant cancer detection rate (Gleason≥3 + 4) was 37% (95% CI 0.24-0.52; I2 = 99%). The rate of infection-related complications in the included studies was 0.15% (95% CI 0.0000-0.0043; I2 = 86). The LA transperineal procedures had a low rate of procedural abandonment (26/6954, 0.37%), with the greatest pain scores measured during LA administration. No formal cost analyses on LA transperineal prostate biopsies were identified in the literature. The overall risk of bias in the included studies was high, with considerable study heterogeneity and publication bias. CONCLUSION: Transperineal prostate biopsy performed under LA is a viable option for centres interested in avoiding the risk of infection associated with transrectal biopsy, and the logistical burden of general anaesthesia. Further investigation into LA transperineal prostate biopsy with comparative studies is warranted for its consideration as the standard in prostate biopsy technique.