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SamenvattingDe MRI-scan van de prostaat heeft de bioptstrategie sterk beïnvloed. Toch kunnen bij een normale MRI biopten geïndiceerd blijven: zowel gerichte als systematische. In deze studie werd geanalyseerd welke prostaattumoren gemist zouden worden in de hypothetische situatie dat er geen systematische biopten genomen waren in ons cohort, en dat de MRI volledig leidend zou zijn geweest in het diagnostisch pad. Als referentie dienden de uitkomsten van het standaardprotocol, waarin alle verwezen patiënten (n = 496) een MRI krijgen, er bij een verhoogde kans op prostaatkanker volgens de ERSPC-prostaatwijzer óf afwijkende MRI biopten worden genomen, en er altijd systematische, plusgerichte biopten worden verricht, indien mogelijk. Uit de analyse bleek dat 16 % van de tumoren met een ISUP-graad ≥2 (≥3 + 4 = 7) gemist zou zijn, maar ook dat slechts 66 % van de patiënten gebiopteerd zou hoeven worden, met 50–75 % minder cores, en dat 52 % van de ISUP-gr 1 (3 + 3 = 6)-tumoren ongedetecteerd zouden blijven.

Introduction The COVID-19 outbreak has become the dominant issue throughout the world whilst the governments, nations and health services are trying to deal with its impact. The aim of our study is to assess the impact of COVID-19 on patients treated with radical prostatectomy (RP) for prostate cancer (PCa) at European referral centers in terms of surgical volume (SV), waiting list meant as time from biopsy to surgery (WL) and risk of adverse pathologic findings at RP due to the selection of men with more adverse disease characteristics at final pathology. Material and methods Consecutive patients with a diagnosis of histologically proven PCa treated with RP between March 2020 (WHO declaration of pandemic) and December 2020 were identified. Patients with metastatic disease not eligible to local treatment and recurrent prostate cancer after RP or RT were excluded. Patients treated at the same institutions between March 2019 and December 2019 were considered as the control group. Multivariable logistic regression analysis tested the impact of the COVID-19 outbreak on the risk of adverse pathologic findings at RP after adjusting for confounders. The percentage change of SV and WL was assessed comparing the months of pandemic with the equivalent timespan of the previous year. Results A total of 2,574 patients treated with RP (927 cases and 1647 controls) were identified in 8 European tertiary referral centers. At multivariable analysis patients who were treated during the pandemic had higher risk of extra prostatic disease (OR:1.35, p = 0.038) and lymph node invasion (LNI) (OR:1.72, p = 0.048). An average 23% reduction of the SV with the equivalent timespan of the previous year allowed an illusory reduction of the WL after the peak gained during the first wave of COVID-19. Conclusions Our results showed that the COVID-19 outbreak resulted in a delay in the administration of curative-intent therapies in patients with localized PCa. This, in turn, resulted in a stage migration phenomenon with a potential impact on oncologic control. Weitere Verfasser:innen aus Einrichtungen außerhalb der Universität Duisburg-Essen sind nicht aufgeführt.

Introduction To establish oncological safe nerve-sparing robot-assisted radical prostatectomy, accurate assessment of extraprostatic extension (EPE) is critical. A recently developed nomogram including magnetic resonance imaging parameters accurately predicted side-specific EPE in the development cohort. The aim of this study is to assess this model's performance in an external patient population. Patients and methods Model fit was assessed in a cohort of 550 patients who underwent robot-assisted radical prostatectomy in 2014 to 2017 for prostate cancer. Model calibration was evaluated using calibration slopes. Discriminative ability was quantified using the area under the receiver operating characteristic curve. Model updating was done by adjusting the linear predictor to minimize differences in expected and observed risk for EPE. Results A total of 792 prostate lobes were included for model validation. Discriminative ability expressed in terms of receiver operating characteristic curve was 0.78, 95%CI 0.75–0.82. Graphical evaluation of the calibration showed poor fit with a high disagreement between predicted probabilities and observed probabilities of EPE in the population. Model updating resulted in excellent agreement between mean predicted and observed probabilities. However, calibration plots showed substantial miscalibration; including both under- and overestimation. Conclusion External validation of the novel nomogram for the prediction of side specific EPE developed by Martini and co-workers showed good discriminative ability but poor calibration. After updating, substantial miscalibration was still present. Use of this nomogram for individualized risk predictions is therefore not recommended.

Background Despite the key importance of magnetic resonance imaging (MRI) parameters, risk classification systems for biochemical recurrence (BCR) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) are still based on clinical variables alone. Objective We aimed at developing and validating a novel classification integrating clinical and radiological parameters. Design, setting, and participants A retrospective multicenter cohort study was conducted between 2014 and 2020 across seven academic international referral centers. A total of 2565 patients treated with RP for PCa were identified. Outcome measurements and statistical analysis Early BCR was defined as two prostate-specific antigen (PSA) values of ≥0.2 ng/ml within 3 yr after RP. Kaplan-Meier and Cox regressions tested time and predictors of BCR. Development and validation cohorts were generated from the overall patient sample. A model predicting early BCR based on Cox-derived coefficients represented the basis for a nomogram that was validated externally. Predictors consisted of PSA, biopsy grade group, MRI stage, and the maximum diameter of lesion at MRI. Novel risk categories were then identified. The Harrel’s concordance index (c-index) compared the accuracy of our risk stratification with the European Association of Urology (EAU), Cancer of the Prostate Risk Assessment (CAPRA), and International Staging Collaboration for Cancer of the Prostate (STAR-CAP) risk groups in predicting early BCR. Results and limitations Overall, 200 (8%), 1834 (71%), and 531 (21%) had low-, intermediate-, and high-risk disease according to the EAU risk groups. The 3-yr overall BCR-free survival rate was 84%. No differences were observed in the 3-yr BCR-free survival between EAU low- and intermediate-risk groups (88% vs 87%; p = 0.1). The novel nomogram depicted optimal discrimination at external validation (c-index 78%). Four new risk categories were identified based on the predictors included in the Cox-based nomogram. This new risk classification had higher accuracy in predicting early BCR (c-index 70%) than the EAU, CAPRA, and STAR-CAP risk classifications (c-index 64%, 63%, and 67%, respectively). Conclusions We developed and externally validated four novel categories based on clinical and radiological parameters to predict early BCR. This novel classification exhibited higher accuracy than the available tools. Patient summary Our novel and straightforward risk classification outperformed currently available preoperative risk tools and should, therefore, assist physicians in preoperative counseling of men candidate to radical treatment for prostate cancer.

Contains fulltext : 251793.pdf (Publisher’s version ) (Closed access) BACKGROUND: Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP). OBJECTIVE: To develop and externally validate nomograms including multiparametric magnetic resonance imaging (mpMRI) information to predict side-specific EPE. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 1870 consecutive prostate cancer patients who underwent robot-assisted RP from 2014 to 2018 at three institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Four multivariable logistic regression models were established, including combinations of patient-based and side-specific variables: prostate-specific antigen (PSA) density, highest ipsilateral International Society of Urological Pathology (ISUP) biopsy grade, ipsilateral percentage of positive cores on systematic biopsy, and side-specific clinical stage assessed by both digital rectal examination and mpMRI. Discrimination (area under the curve [AUC]), calibration, and net benefit of these models were assessed in the development cohort and two external validation cohorts. RESULTS AND LIMITATIONS: On external validation, AUCs of the four models ranged from 0.80 (95% confidence interval [CI] 0.68-0.88) to 0.83 (95% CI 0.72-0.90) in cohort 1 and from 0.77 (95% CI 0.62-0.87) to 0.78 (95% CI 0.64-0.88) in cohort 2. The three models including mpMRI staging information resulted in relatively higher AUCs compared with the model without mpMRI information. No major differences between the four models regarding net benefit were established. The model based on PSA density, ISUP grade, and mpMRI T stage was superior in terms of calibration. Using this model with a cut-off of 20%, 1980/2908 (68%) prostatic lobes without EPE would be found eligible for nerve sparing, whereas non-nerve sparing would be advised in 642/832 (77%) lobes with EPE. CONCLUSIONS: Our analysis resulted in a simple and robust nomogram for the prediction of side-specific EPE, which should be used to select patients for nerve-sparing RP. PATIENT SUMMARY: We developed a prediction model that can be used to assess accurately the likelihood of tumour extension outside the prostate. This tool can guide patient selection for safe nerve-sparing surgery.

Current guidelines do not provide strong recommendations on preservation of the neurovascular bundles during radical prostatectomy in case of high-risk (HR) prostate cancer and/or suspicious extraprostatic extension (EPE). We aimed to evaluate when, in case of unilateral HR disease, contralateral nerve sparing (NS) should be considered or not.Within a multi-institutional data set we selected patients with unilateral HR prostate cancer, defined as unilateral EPE and/or seminal vesicle invasion (SVI) on multiparametric (mp) magnetic resonance imaging (MRI), or unilateral International Society of Urologic Pathologists (ISUP) 4-5 or prostate specific antigen ≥20 ng/ml. To evaluate when to perform NS based on the risk of contralateral EPE, we relied on chi-square automated interaction detection, a recursive machine-learning partitioning algorithm developed to identify risk groups, which was fit to predict the presence of EPE on final pathology, contralaterally to the prostate lobe with HR disease.A total of 705 patients were identified. Contralateral EPE was documented in 87 patients (12%). Chi-square automated interaction detection identified 3 groups, consisting of 1) absence of SVI on mpMRI and index lesion diameter ≤15 mm, 2) index lesion diameter ≤15 mm and contralateral ISUP 2-3 or index lesion diameter15 mm and negative contralateral biopsy or ISUP 1, and 3) SVI on mpMRI or index lesion diameter15 mm and contralateral biopsy ISUP 2-3. We named those groups as low, intermediate and high-risk, respectively, for contralateral EPE. The rate of EPE and positive surgical margins across the groups were 4.8%, 14% and 26%, and 5.6%, 13% and 18%, respectively.Our study challenges current guidelines by proving that wide bilateral excision in men with unilateral HR disease is not justified. Pending external validation, we propose performing NS and incremental NS in case of contralateral low and intermediate EPE risk, respectively.

SamenvattingHet is tijd om afstand te doen van de traditionele computertomografie (CT) en de botscan voor disseminatieonderzoek bij hoogrisico primair prostaatcarcinoom en deze te vervangen door prostaatspecifiek membraanantigeen positive emission tomography (PSMA PET) CT.

Active surveillance (AS) is a safe treatment strategy for men with low-risk prostate cancer (PC) when performed in a research setting using strict follow-up. However, less is known about the protocol adherence and outcomes for AS in real-world practice.To evaluate Prostate Cancer Research International Active Surveillance (PRIAS) protocol adherence in a real-world cohort and to relate follow-up intensity to oncological safety.Patients with biopsy-detected PC diagnosed from 2008 to 2014 treated with AS at six teaching hospitals in The Netherlands.AS included regular prostate-specific antigen (PSA) testing (every 3-6mo) combined with a confirmatory biopsy 1yr after diagnosis and every 3yr thereafter.The proportions of patients complying with the PRIAS biopsy and PSA monitoring protocol were determined. We assessed if PRIAS-discordant follow-up was associated with a higher risk of metastasis compared with PRIAS-concordant follow-up using Cox regression analysis. Analysis was performed for separate risk groups (PRIAS-eligible and PRIAS-ineligible) on the basis of the PRIAS inclusion criteria.Of all patients on AS for6mo, 706/958 (74%) had PRIAS-concordant PSA monitoring. Overall concordant follow-up (PSA and repeat biopsy) was observed in 415/958 patients (43%). The percentage of patients with overall concordant follow-up varied between hospitals (range 34-60%; p0.001). Among PRIAS-ineligible patients, PRIAS-discordant PSA monitoring was associated with a higher risk of developing PC metastases during AS compared with patients with concordant follow-up (hazard ratio 5.25, 95% confidence interval 1.02-27.1). In the PRIAS-eligible population, we found no significant differences regarding rates of metastases between patients with discordant and concordant follow-up.We observed substantial variation in AS follow-up intensity between large urological practices in the Netherlands. Overall, 43% of patients on AS in daily clinical practice receive PRIAS-concordant follow-up. Noncompliance with the PRIAS follow-up protocol was associated with a higher rate of metastasis among PRIAS-ineligible patients, indicating that strict protocol adherence is important when these patients opt for AS.Fewer than half of patients with prostate cancer on active surveillance are monitored according to the follow-up protocol of the largest ongoing active surveillance study. Lower-intensity monitoring may be less safe for patients who are not in the lowest risk group.

To date, only one trial compared focal therapy and active surveillance (AS) for low-risk prostate cancer (PCa). In addition, long-term outcomes of focal cryotherapy (FC) are lacking.Our aim was to evaluate long-term outcomes of FC and compare them with AS.We included two prospective series of 121 (FC) and 459 (AS) consecutive patients (2008-2018) for low- to intermediate-risk PCa.Study outcomes were radical therapy-free or androgen deprivation therapy (ADT)-free, any treatment-free, metastasis-free, and overall survival. A matched pair analysis was performed using seven covariates.The median FC follow-up was 85 mo (interquartile range 58-104); 92 (76%) men had International Society of Urological Pathology (ISUP) grade 1. Among matched variables, no significant differences were present except for cT stage and year of entry (both p0.01). Ten-year radical therapy-free or ADT-free, any treatment-free, metastasis-free, and overall survival were 51%, 40.2%, 93.9%, and 97%, respectively for FC. No differences were noted with AS (all p0.05), with the exception of time to radical therapy, time to radical therapy and ADT, and time to any treatment, all being shorter for AS (all p0.01). Freedom from radical treatment or ADT was higher for FC (AS 10 yr 39.3%; p = 0.04). Complications were relatively rare (26.5%) and mainly of low grade (Clavien2, n = 3); three men developed incontinence (p = 0.0814), while both International Index of Erectile Function 5 and International Prostate Symptom Score scores increased (p = 0.0287 and p = 0.0165, respectively). Limitations include absence of randomization.At an early long-term follow-up, FC in the context of mainly low-risk PCa is safe and increases time to radical therapy but does not provide meaningful oncological advantages compared with AS.We compared focal cryotherapy with active surveillance mainly for low-risk prostate cancer. Focal cryotherapy, despite having fewer complications, did not yield meaningful advantages over active surveillance at 10 yr. Active surveillance should be preferred to focal cryotherapy for these patients.

Contains fulltext : 237659.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To evaluate the impact of using clinical stage assessed by multiparametric magnetic resonance imaging (mpMRI) on the performance of two established nomograms for the prediction of pelvic lymph node involvement (LNI) in patients with prostate cancer. PATIENTS AND METHODS: Patients undergoing robot-assisted extended pelvic lymph node dissection (ePLND) from 2015 to 2019 at three teaching hospitals were retrospectively evaluated. Risk of LNI was calculated four times for each patient, using clinical tumour stage (T-stage) assessed by digital rectal examination (DRE) and by mpMRI, in the Memorial Sloan Kettering Cancer Centre (MSKCC; 2018) and Briganti (2012) nomograms. Discrimination (area under the curve [AUC]), calibration, and the net benefit of these four strategies were assessed and compared. RESULTS: A total of 1062 patients were included, of whom 301 (28%) had histologically proven LNI. Using DRE T-stage resulted in AUCs of 0.71 (95% confidence interval [CI] 0.70-0.72) for the MSKCC and 0.73 (95% CI 0.72-0.74) for the Briganti nomogram. Using mpMRI T-stage, the AUCs were 0.72 (95% CI 0.71-0.73) for the MSKCC and 0.75 (95% CI 0.74-0.76) for the Briganti nomogram. mpMRI T-stage resulted in equivalent calibration compared with DRE T-stage. Combined use of mpMRI T-stage and the Briganti 2012 nomogram was shown to be superior in terms of AUC, calibration, and net benefit. Use of mpMRI T-stage led to increased sensitivity for the detection of LNI for all risk thresholds in both models, countered by a decreased specificity, compared with DRE T-stage. CONCLUSION: T-stage as assessed by mpMRI is an appropriate alternative for T-stage assessed by DRE to determine nomogram-based risk of LNI in patients with prostate cancer, and was associated with improved model performance of both the MSKCC 2018 and Briganti 2012 nomograms.

Background: The Movember funded TrueNTH Global Registry (TNGR) aims to improve care by collecting and analysing a consistent dataset to identify variation in disease management, benchmark care delivery in accordance with best practice guidelines and provide this information to those in a position to enact change. We discuss considerations of designing and implementing a quality of care report for TNGR. Methods: Eleven working group sessions were held prior to and as reports were being built with representation from clinicians, data managers and investigators contributing to TNGR. The aim of the meetings was to understand current data display approaches, share literature review findings and ideas for innovative approaches. Preferred displays were evaluated with two surveys (survey 1: 5 clinicians and 5 non-clinicians, 83% response rate; survey 2: 17 clinicians and 18 non-clinicians, 93% response rate). Results: Consensus on dashboard design and three data-display preferences were achieved. The dashboard comprised two performance summary charts; one summarising site’s relative quality indicator (QI) performance and another to summarise data quality. Binary outcome QIs were presented as funnel plots. Patient-reported outcome measures of function score and the extent to which men were bothered by their symptoms were presented in bubble plots. Time series graphs were seen as providing important information to supplement funnel and bubble plots. R Markdown was selected as the software program principally because of its excellent analytic and graph display capacity, open source licensing model and the large global community sharing program code enhancements. Conclusions: International collaboration in creating and maintaining clinical quality registries has allowed benchmarking of process and outcome measures on a large scale. A registry report system was developed with stakeholder engagement to produce dynamic reports that provide user-specific feedback to 132 participating sites across 13 countries.

In daily practice, a wider range of patients with prostate cancer (PCa) are selected for active surveillance (AS) compared to those in AS trials, including higher-risk patients. However, less is known about the outcomes for off-protocol selected PCa patients who opt for AS.To compare AS outcomes for higher-risk patients and very low-risk patients in a large cohort of patients diagnosed with PCa.Patients diagnosed with PCa between 2008 and 2015 with clinical stage ≥T1c and managed with AS at six large teaching hospitals.AS included regular prostate-specific antigen (PSA) testing (every 3-6 mo) and a confirmatory biopsy 1 yr after diagnosis and every 3 yr thereafter.Using the inclusion criteria of the PRIAS study, outcomes for PRIAS-eligible patients (ie, cT1c-T2, Gleason sum score ≤6, ≤2 positive biopsy cores, PSA ≤10 ng/ml, and PSA density0.2 ng/ml/ml) were compared to outcomes for PRIAS-ineligible patients. Unfavourable outcomes following deferred surgery, biochemical recurrence, and risk of metastasis were calculated using univariate and multivariate Cox regression analyses. Time to tumour progression was established using survival analysis.Of the 1000 patients included and managed with AS, almost half of the patients (49%) had higher-risk disease characteristics than the PRIAS inclusion criteria. PRIAS-ineligible patients discontinued AS because of tumour progression significantly earlier than PRIAS-eligible patients (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.44-2.11); they also had a higher risk of positive surgical margins (odds ratio [OR] 2.15, 95% CI 1.11-4.17) and unfavourable pathological findings (OR 3.20, 95% CI 1.61-6.35) following deferred radical prostatectomy. PSA density ≥0.2 ng/ml/ml was the most important individual predictor and, in addition to a higher risk of tumour progression and unfavourable surgical outcomes, was also associated with a significantly higher risk of biochemical progression following deferred radical prostatectomy (OR 3.26, 95% CI 1.23-8.64). In the overall population, PSA density ≥0.2 ng/ml/ml was also associated with a higher risk of metastasis (HR 2.71, 95% CI 1.23-5.96).In this cohort, approximately half of the patients did not meet the inclusion criteria of the PRIAS study. These patients had a two- to threefold higher risk of disease progression and unfavourable outcomes following deferred prostatectomy. PSA density is an important individual predictor of unfavourable outcomes and should be taken into account when selecting patients for AS.A large proportion of patients with prostate cancer on active surveillance are not in the lowest risk group. These patients have a higher risk of experiencing tumour progression to a stage requiring curative intervention. They also have worse disease prognosis compared to patients on active surveillance in the lowest risk group.

PURPOSE: Urethral reconstruction is performed for urethral stricture or hypospadias correction. Research on urethral tissue engineering is increasing. Because the corpus spongiosum is important to support the urethra, urethral tissue engineering should ideally be combined with reconstruction of a corpus spongiosum. We describe a method to visualize and measure the architecture of the corpus spongiosum, which is needed for scaffold design. MATERIALS AND METHODS: The penis was dissected from 2 unembalmed male cadavers. One penis was flaccid and the other was erect, as induced by saline infusion. Both were frozen in ice. At 6 sites sections were obtained in the transverse and frontal directions. After digitalizing the stained sections the images were edited, area measurements were taken and a 3-dimensional reconstruction was made. RESULTS: In transverse sections the mean area of the vascular lumen was 60% and 77% in the flaccid and the erect corpus spongiosum, and in frontal sections it was 53% and 74%, respectively. This indicated a 129% transverse increase and a 140% longitudinal increase in erection. Section sites did not essentially differ except in the glans penis. Frontal sections showed larger vascular cavities and more incomplete septae than transverse sections. CONCLUSIONS: This study provides what is to our knowledge novel information on corpus spongiosum architecture, which is relevant for scaffold design in tissue engineering. The study protocol can be used in future research with a larger number of specimens and more extensive analyses.

Objectives To evaluate treatment results of electroejaculation in patients with spinal cord injuries and the additional value of repeated electroejaculation. Methods We carried out a retrospective chart analysis of all spinal cord injury patients treated with electroejaculation at University Medical Center Utrecht, Utrecht, the Netherlands, from January 1994 to January 2015. Data were collected on the patients’ demographics and medical history. We evaluated sperm quality according to World Health Organization standards, pregnancy and delivery rates. Results A total of 230 electroejaculation procedures were carried out in 47 patients. In 227 of 230 electroejaculations (98.7%), an ejaculate could be obtained. In 169 of 230 (73.5%) electroejaculation procedures, it was possible to yield semen containing progressively motile spermatozoa. In 18 of 47 (38.3%) patients, no semen of sufficient quality could be yielded during the first electroejaculation. Repeated electroejaculation resulted in ejaculates containing progressively motile spermatozoa in seven of 18 (38.9%) of these men. Procreation was attempted through in vitro fertilization/intracytoplasmic sperm injection in 17 couples; of these, 14 of 17 (82.4%) couples achieved pregnancy. Conclusions In the majority of spinal cord injury patients treated with electroejaculation, it is possible to obtain semen that can be used for assisted reproductive technologies. Repeated electroejaculation should be considered when the first procedure fails.

Gedetailleerde kennis van de architectuur van het corpus spongiosum is nodig voor tissue engineering, maar ontbreekt. Twee penissen van overleden mannen die hun lichaam ter beschikking van de wetenschap hadden gesteld werden ingevroren; een penis in slappe toestand, de ander artificieel in erectie gebracht. Transversale en frontale (lengterichting) weefselcoupes werden genomen en gekleurd. Na digitalisering werden oppervlakten, vorm en weefseldichtheid gemeten en vergeleken. Ook werden een digitale en een stereolithografische 3D-reconstructie gemaakt. Oppervlaktepercentages van vasculaire holten in beide richtingen lieten een oppervlaktetoename zien in erectie van 127 % transversaal en 140 % frontaal. De transversale coupes hadden een vergelijkbare structuur op de verschillende locaties, maar een grotere weefseldichtheid in de glans penis. De vasculaire holten waren groter in de frontale coupes met meer incomplete septae. Dit werd bevestigd in de 3D-modellen. Deze studie geeft informatie over de architectuur van het corpus spongiosum, die belangrijk is bij tissue engineering.