Transperineal template saturation and conventional biopsy for stage prediction in prostate cancer

OBJECTIVE To evaluate the performance of risk calculators (RCs) predicting lymph node invasion (LNI) and extraprostatic extension (EPE) in men undergoing transperineal magnetic resonance imaging/transrectal ultrasound (TRUS)-fusion template saturation biopsy (TTSB) and conventional systematic TRUS-guided biopsy (SB). PATIENTS AND METHODS The RCs were tested in a consecutive cohort of 645 men undergoing radical prostatectomy with extended pelvic LN dissection between 2005 and 2019. TTSB was performed in 230 (35.7%) and SB in 415 (64.3%) men. Risk of LNI and EPE was calculated using the available RCs. Discrimination, calibration, and clinical usefulness stratified by different biopsy techniques were assessed. RESULTS Lymph node invasion was observed in 23 (10%) and EPE in 73 (31.8%) of cases with TTSB and 53 (12.8%) and 158 (38%) with SB, respectively. RCs showed an excellent discrimination and acceptable calibration for prediction of LNI based on TTSB (area under the curve [AUC]/risk estimation: Memorial Sloan Kettering Cancer Center [MSKCC]-RC 0.79/-4%, Briganti (2012)-RC 0.82/-4%, Gandaglia-RC 0.81/+6%). These were comparable in SB (MSKCC-RC 0.78/+2%; Briganti (2012)-RC 0.77/-3%). Decision curve analysis (DCA) revealed a net benefit at threshold probabilities between 3% and 6% when TTSB was used. For prediction of EPE based on TTSB an inferior discrimination and variable calibration were observed (AUC/risk estimation: MSKCC-RC 0.71/+8% and Martini (2018)-RC 0.69/+2%) achieving a net benefit on DCA only at risk thresholds of >17%. Performance of RCs for prediction of LNI and EPE based on SB showed comparable results with a better performance in the DCA for LNI (risk thresholds 1-2%) and poorer performance for EPE (risk threshold >20%). This study is limited by its retrospective single-institution design. CONCLUSIONS The potentially more accurate grading ability of TTSB did not result in improved performance of preoperative RCs. Prediction tools for LNI proved clinical usefulness while RCs for EPE did not

Outcomes of robot-assisted laparoscopic extended pelvic lymph node dissection for prostate Cancer

Introduction Extended pelvic lymph node dissection (ePLND) in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) is a widely used procedure. However, little is known about anatomical site-specific yields and subsequent metastatic patterns in these patients. Patients and methods Data on a consecutive series of 1107 patients undergoing RARP at our centre between 2004 and 2018 were analysed. In men undergoing LN dissection, the internal, external and obturator nodes were removed and sent in separately. We performed an analysis of LN yields in total and for each anatomical zone, patterns of LN metastases and complications. Oncological outcome in pN+ disease was assessed including postoperative PSA persistence and survival. Results A total of 823 ePLNDs were performed in the investigated cohort resulting in 98 men being diagnosed as pN+ (8.9%). The median (IQR) LN yield was 19 (14–25), 10 (7–13) on the right and 9 (6–12) on the left side (P < 0.001). A median of six (4–8) LNs were retrieved from the external, three (1–6) from the internal iliac artery, and eight (6–12) from the obturator fossa. More men had metastatic LNs on the right side compared to the left (41 vs. 19). Symptomatic lymphoceles occurred exclusively in the ePLND group (2.3% vs. 0%, p = 0.04). Postoperatively, 47 (47.9%) of men with pN+ reached a PSA of < 0.1μg/ml. There was no association between a certain pN+ region and postoperative PSA persistence or BCRFS. The estimated cancer specific survival rate at 5 years was 98.5% for pN+ disease. Conclusion Robot-assisted laparoscopic ePLND with a high LN yield and low complication rate is feasible. However, we observed an imbalance in more removed and positive LNs on the right side compared to the left. A high rate of postoperative PSA persistence and early recurrence in pN+ patients might indicate a possibly limited therapeutical value of the procedure in already spread disease. Yet, these men demonstrated an excellent survival

Therapy decisions after diagnosis of prostate cancer in men with negative prostate MRI

Background: To investigate the clinical implications of magnetic resonance imaging (MRI) negative prostate cancer (PCa) in a cohort of men undergoing transperineal prostate biopsy. Methods: We included all men without prior diagnosis of PCa undergoing transperineal template saturation ± fusion-guided targeted biopsy of the prostate between November 2014 and March 2018. Before biopsy, all patients underwent MRI and biopsies were performed irrespective of imaging results. Baseline characteristics, imaging, biopsy results, and follow-up information were retrieved from the patient charts. Patients were classified as either MRI negative (Prostate Imaging Reporting and Data System [PIRADS] ≤ 2) or positive (PIRADS ≥ 3). ISUP grade group 1 was defined as clinically nonsignificant (nsPCa) and ≥2 as clinically significant PCa (csPCa). Primary outcome was the individual therapeutic decision after diagnosis of PCa stratified according to MRI visibility. Secondary outcomes were the sensitivity and specificity of MRI, and the urooncological outcomes after radical prostatectomy (RP). Results: From 515 patients undergoing prostate biopsy, 171 (33.2%) patients had a negative and 344 (66.8%) a positive MRI. Pathology review stratified for MRI negative and positive cases revealed nsPCa in 27 (15.8%) and 32 (9.3%) and csPCa in 26 (15.2%) and 194 (56.4%) of the patients, respectively. The rate of active treatment in the MRI negative was lower compared with the MRI positive cohort (12.3% vs. 53.2%; odd ratio [OR] = 0.12; p < 0.001). While men with negative MRI were more likely to undergo active surveillance (AS) than MRI positive patients (18.1% vs. 10.8%; OR = 1.84; p = 0.027), they rarely underwent RP (6.4% vs. 40.7%, OR = 0.10; p < 0.001). Logistic regression revealed that a negative MRI was independently protective for active treatment (OR = 0.32, p = 0.014). The specificity, sensitivity, negative, and positive predictive value of MRI for detection of csPCa were 49.2%, 88.2%, 56.4%, and 84.8%, respectively. The rate of adverse clinicopathological outcome features (pT3/4, ISUP ≥4, or prostate-specific antigen [PSA]-persistence) following RP was 4.7% for men with MRI negative compared to 17.4% for men with MRI positive PCa (OR = 3.1, p = 0.19). Conclusion: Only few men with MRI negative PCa need active cancer treatment at the time of diagnosis, while the majority opts for AS. Omitting prostate biopsies and performing a follow-up MRI may be a safe alternative to reduce the number of unnecessary interventions. Keywords: PIRADS; biopsy-naïve; imaging; invisible prostate cancer; transperineal biopsy; treatmen

Intrafascial dissection significantly increases positive surgical margin and biochemical recurrence rates after robotic-assisted radical prostatectomy

Introduction: Improved visualization and magnification in robot-assisted laparoscopic radical prostatectomy (RALRP) has tempted many urologists to dissect the neurovascular bundle closer to the prostate following the layers of the pseudo-capsule of the prostate. This might bear a higher risk of decreased tumor control. Materials and Methods: An analysis of a consecutive series of 186 patients who underwent RALRP at our institution was performed. The outcome of patients with intrafascial nerve-sparing (INS) was compared with the outcome of patients who underwent interfascial, extrafascial or no nerve-sparing (non-INS). Results: A total of 80 patients (43.0%) received INS. The overall R1 rate was 27.9%. For pT2 tumors the rate of R1 was 33.8% in INS versus 14.8% in non-INS (odds ratio 2.936, 95% confidence interval 1.338-6.443, p = 0.007). Recurrence-free survival was significantly shorter in INS (p = 0.05; hazard ratio 3.791). Conclusion: The intrafascial dissection technique for RALRP bears a high risk of incomplete resection in localized prostate cancer resulting in unfavorable outcome

Prostate cancer screening in Switzerland: a literature review and consensus statement from the Swiss Society of Urology

Over a decade ago, the United States Preventive Services Taskforce (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer in all men, which considerably influenced prostate cancer screening policies worldwide after that. Consequently, the world has seen increasing numbers of advanced stages and prostate cancer deaths, which later led the USPSTF to withdraw its initial statement. Meanwhile, the European Union has elaborated a directive to address the problem of implementing prostate cancer screening in “Europe’s Beating Cancer Plan”. In Switzerland, concerned urologists formed an open Swiss Prostate Cancer Screening Group to improve the early detection of prostate cancer. On the 20th of September 2023, during the annual general assembly of the Swiss Society of Urology (SGU/SSU) in Lausanne, members positively voted for a stepwise approach to evaluate the feasibility of implementing organised prostate cancer screening programs in Switzerland. The following article will summarise the events and scientific advances in the last decade during which evidence and promising additional modalities to complement PSA-based prostate cancer screening have emerged. It also aims to provide an overview of contemporary strategies and their potential harms and benefits

External Validation and Comparison of Prostate Cancer Risk Calculators Incorporating Multiparametric Magnetic Resonance Imaging for Prediction of Clinically Significant Prostate Cancer

PURPOSE: To externally validate recently published prostate cancer risk calculators (PCa-RCs) incorporating multiparametric magnetic resonance imaging (mpMRI) for the prediction of clinically significant prostate cancer (csPCa) and compare their performance to mpMRI-naïve PCa-RCs. MATERIAL AND METHODS: Men without previous PCa diagnosis undergoing transperineal template saturation prostate biopsy with fusion-guided targeted biopsy between 11/2014 and 03/2018 in our academic tertiary referral center were identified. Any Gleason pattern ≥4 was defined to be csPCa. Predictors (age, PSA, DRE, prostate volume, family history, previous prostate biopsy and highest region of interest according to PIRADS) were retrospectively collected. Four mpMRI-PCa-RCs and two mpMRI-naïve PCa-RCs were evaluated for their discrimination, calibration and clinical net benefit using a ROC analysis, calibration plots and a decision curve analysis, respectively. RESULTS: Out of 468 men, 193 (41%) were diagnosed with csPCa. Three mpMRI-PCa-RCs showed similar discrimination with area-underneath-the-receiver-operating-characteristic-curves (AUC) from 0.83 to 0.85, which was significantly higher than the other PCa-RCs (AUCs: 0.69-0.74). Calibration-in-the-large showed minimal deviation from the true amount of csPCa by 2% for two mpMRI-PCa-RCs, while the other PCa-RCs showed worse calibration (11-27%). A clinical net benefit could only be observed for three mpMRI-PCa-RCs at biopsy thresholds ≥15%, while none of the six investigated PCa-RCs demonstrated clinical utility against a biopsy all strategy at thresholds <15%. CONCLUSIONS: Performance of the mpMRI-PCa-RCs varies, but they generally outperform mpMRI-naïve PCa-RCs in regard to discrimination, calibration and clinical usefulness. External validation in other biopsy settings is highly encouraged

68 Ga-PSMA-11 PET/MRI versus multiparametric MRI in men referred for prostate biopsy: primary tumour localization and interreader agreement

Background: Magnetic resonance imaging (MRI) is recommended by the European Urology Association guidelines as the standard modality for imaging-guided biopsy. Recently positron emission tomography with prostate-specific membrane antigen (PSMA PET) has shown promising results as a tool for this purpose. The aim of this study was to compare the accuracy of positron emission tomography with prostate-specific membrane antigen/magnetic resonance imaging (PET/MRI) using the gallium-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and multiparametric MRI (mpMRI) for pre-biopsy tumour localization and interreader agreement for visual and semiquantitative analysis. Semiquantitative parameters included apparent diffusion coefficient (ADC) and maximum lesion diameter for mpMRI and standardized uptake value (SUVmax) and PSMA-positive volume (PSMAvol) for PSMA PET/MRI. Results: Sensitivity and specificity were 61.4% and 92.9% for mpMRI and 66.7% and 92.9% for PSMA PET/MRI for reader one, respectively. RPE was available in 23 patients and 41 of 47 quadrants with discrepant findings. Based on RPE results, the specificity for both imaging modalities increased to 98% and 99%, and the sensitivity improved to 63.9% and 72.1% for mpMRI and PSMA PET/MRI, respectively. Both modalities yielded a substantial interreader agreement for primary tumour localization (mpMRI kappa = 0.65 (0.52-0.79), PSMA PET/MRI kappa = 0.73 (0.61-0.84)). ICC for SUVmax, PSMAvol and lesion diameter were almost perfect (≥ 0.90) while for ADC it was only moderate (ICC = 0.54 (0.04-0.78)). ADC and lesion diameter did not correlate significantly with Gleason score (ρ = 0.26 and ρ = 0.16) while SUVmax and PSMAvol did (ρ = - 0.474 and ρ = - 0.468). Conclusions: PSMA PET/MRI has similar accuracy and reliability to mpMRI regarding primary prostate cancer (PCa) localization. In our cohort, semiquantitative parameters from PSMA PET/MRI correlated with tumour grade and were more reliable than the ones from mpMRI. Keywords: ADC; Biopsy guidance; Interreader agreement; PET/MRI; PSMA PET; Primary staging; SUVmax; Targeted biopsy; Template biopsy; mpMRI

Morbidity and mortality after robot-assisted radical cystectomy with intracorporeal urinary diversion in octogenarians: results from the European Association of Urology Robotic Urology Section Scientific Working Group

OBJECTIVES: To evaluate the postoperative complication and mortality rate following laparoscopic radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) in octogenarians. PATIENTS AND METHODS: We conducted a retrospective analysis comparing postoperative complication and mortality rates depending on age in a consecutive series of 1890 patients who underwent RARC with ICUD for bladder cancer between 2004 and 2018 in 10 European centres. Outcomes of patients aged <80 years and those aged ≥80 years were compared with regard to postoperative complications (Clavien–Dindo grading) and mortality rate. Cancer-specific mortality (CSM) and other-cause mortality (OCM) after surgery were calculated using the non-parametric Aalen-Johansen estimator. RESULTS: A total of 1726 patients aged <80 years and 164 aged ≥80 years were included in the analysis. The 30- and 90-day rate for high-grade (Clavien–Dindo grades III–V) complications were 15% and 21% for patients aged <80 years compared to 11% and 13% for patients aged ≥80 years (P = 0.2 and P = 0.03), respectively. In a multivariable logistic regression analysis adjusting for pre- and postoperative variables, age ≥80 years was not an independent predictor of high-grade complications (odds ratio 0.6, 95% confidence interval 0.3–1.1; P = 0.12). The non-cancer-related 90-day mortality was 2.3% for patients aged ≥80 years and 1.8% for those aged <80 years, respectively (P = 0.7). The estimated 12-month CSM and OCM rates for those aged <80 years were 8% and 3%, and for those aged ≥80 years, 15% and 8%, respectively (P = 0.009 and P < 0.001). CONCLUSIONS: The minimally invasive approach to RARC with ICUD for bladder cancer in well-selected elderly patients (aged ≥80 years) achieved a tolerable high-grade complication rate; the 90-day postoperative mortality rate was driven by cancer progression and the non-cancer-related rate was equivalent to that of patients aged <80 years. However, an increased OCM rate in this elderly group after the first year should be taken into account. These results will support clinicians and patients when balancing cancer-related vs treatment-related risks and benefits

Periostin is up-regulated in high grade and high stage prostate cancer

BACKGROUND: Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. METHODS: Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93) and a test cohort (n = 325). Metastatic prostate cancers (n = 20), hormone refractory prostate cancers (n = 19) and benign prostatic tissues (n = 38) were also analyzed. RESULTS: In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p < 0.01) and advanced tumour stage (p < 0.05) in the test cohort. Whereas periostin expression was weak or absent in the stroma around normal prostate glands, strong periostin expression in tumour stroma was found in most primary and metastatic prostate cancers. High stromal periostin expression was associated with higher Gleason scores (p < 0.001). There was a relationship between stromal periostin expression and shortened PSA relapse free survival times in the training cohort (p < 0.05). CONCLUSIONS: Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer

MAGE-C2/CT10 Protein Expression Is an Independent Predictor of Recurrence in Prostate Cancer

The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity) and castration-resistant prostate cancer (17% positivity; p<0.001). Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015), which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05). MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer