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SamenvattingDoel van de studie was evaluatie van de beschikbare literatuur over de kans op succes van urinedeviaties al dan niet met cystectomie bij patiënten met bekkenpijnsyndroom / interstitiële cystitis. Er werden drie reviews gevonden en nul gerandomiseerde trials. In de 21 geselecteerde case series werden in totaal 475 patiënten geïncludeerd. De kans op succes van een urinedeviatie was 81%. Voorspellers voor de kans op succes (aanwezigheid van een Hunnerse laesie en kleine blaascapaciteit) konden niet worden bevestigd vanwege de heterogeniteit van de studies. Urinedeviatie in combinatie met verwijdering van de blaas was na cystectomie succesvol in 96% van de gevallen, na partiële cystectomie in 75% en na urinedeviatie en zonder cystectomie in 79% van de gevallen. Concluderend kan worden gesteld dat harde wetenschappelijke onderbouwing voor of tegen een urinedeviatie bij bekkenpijnsyndroom / interstitiële cystitis ontbreekt, omdat de (best goede) resultaten in de case series alleen kunnen worden geïnterpreteerd met inachtneming van (inclusie)bias. Op grond hiervan moeten therapiekeuzes nog steeds op individuele basis worden gemaakt.

SamenvattingDoel van deze studie was de klinische toepasbaarheid van 3D-modellen onderzoeken in de preoperatieve planning van robotgeassisteerde radicale laparoscopische prostatectomie (RALP). Er werden 20 virtuele 3D-modellen en 3D-prints gemaakt, waarna 7 urologen op basis hiervan de mate van zijdespecifieke zenuwsparing bepaalden. Vervolgens werden de mate van zenuwsparing per zijde per modaliteit en de absolute overeenkomst in de geplande zenuwsparing tussen urologen geanalyseerd, waaruit bleek dat er tussen de urologen een klinisch-relevant verschil was in de mate van preoperatieve zijdespecifieke zenuwsparing tussen MRI en de virtuele modellen en MRI en de 3D-prints in 25 en 26% van de gevallen met een intraclasscorrelatiecoëfficient van 0,40 (95%-BI 0,28–0,55) voor MRI, van 0,52 (0,39–0,66) voor virtuele 3D-modellen en van 0,58 (0,45–0,71) voor 3D-prints. De conclusie is dat de 3D-modellen een klinisch-relevante impact hebben op de preoperatieve planning van zenuwsparing bij RALP.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5 mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p

Objective: Surgical outcomes are dependent on multiple factors. Besides patient-related or procedure-related factors, several surgeon-related factors contribute to surgical outcomes. The Surgery Task Load Index (SURG-TLX) questionnaire helps to assess the impact of several stressors on the perceived demands of surgeons during surgery. In this study, we evaluate the applicability of the SURG-TLX questionnaire for endourologic procedures and set a first point of reference. Materials and Methods: Between March and August 2022, 15 urologists and urology residents at a tertiary referral center for endourology completed the SURG-TLX questionnaire after endourologic procedures. After data acquisition, all participants were asked to evaluate the applicability of the questionnaire for endourologic procedures. Results: A total of 130 procedures were included between March and August 2022. Situational stress had the lowest median score (3.0/20; interquartile range [IQR] 2.0-7.0) and task complexity the highest (5.0/20; IQR 3.0-8.0). After weighing, the dimensions showed different proportions when compared with the nonweighted scores. Distractions received the highest score (15.0/100; IQR 7.5-32.8), temporal demands (6.0/100; IQR 3.0-12.5), and situational stress the lowest (6.0/100; IQR 2.0-21.0). This was caused by the higher weight that was attributed to distractions (3.4/5), as opposed to task complexity (2.6/5). In the questionnaire regarding applicability of the SURG-TLX, the overall satisfaction (6.0/10; IQR 5.0-7.0) and clarity (6.5/10; IQR 5.0-7.5) were moderate. The user-friendliness and applicability of the questionnaire were rated high (7.0/10; IQR 5.5-8.0 and 7.0/10; IQR 6.0-8.0, respectively) and task load (3.0/10; IQR 2.0-5.0) and time load (2.0/10; IQR 2.0-3.5) low. Conclusion: The SURG-TLX questionnaire is appropriate to assess the different dimensions of workload during endourologic procedures. Furthermore, the perceived workload during endourologic procedures is relatively low.

Contains fulltext : 294430.pdf (Publisher’s version ) (Open Access) BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p

Background The development of accurate urinary biomarkers for non-invasive and cost-effective detection of primary and recurrent bladder tumours is recognized as one of the major clinical needs in bladder cancer diagnostics. The purposes of this study were (1) to validate the results of a previous technical comparison by determining the diagnostic performance of nine methylation markers in urine pellet compared to full void urine, and (2) to validate the diagnostic performance of the optimal marker panel GHSR/MAL from a previous exploratory study in a preclinical setting. Methods Urine samples of 108 patients with bladder cancer and 100 age- and gender-matched controls were prospectively collected for methylation analysis. Urinary methylation levels of the markers FAM19A4, GHSR, MAL, miR-129, miR-935, PHACTR3, PRDM14, SST and ZIC1 were determined with quantitative methylation-specific PCR in urine pellet. Area under the curves (AUCs) were determined for individual markers and the marker panel GHSR/MAL. The diagnostic performance of the marker panel GHSR/MAL was evaluated in the total study population and in different subgroups of patients with bladder cancer using the Chi-square test. The diagnostic accuracy was assessed by leave-one-out cross-validation. Results All nine urinary methylation markers (FAM19A4, GHSR, MAL, miR-129, miR-935, PHACTR3, PRDM14, SST and ZIC1) showed significantly higher methylation levels in bladder cancer patients than in controls (p GHSR/MAL reached an AUC of 0.89 (95% confidence interval [CI] 0.84–0.94), at 80% sensitivity and 93% specificity. Sensitivity of GHSR/MAL increased with higher tumour grades, higher tumour stages, in primary vs. recurrent tumours, and in males vs. females. Conclusions This technical validation supports the robustness of DNA methylation analysis in urine pellet and full void urine for the non-invasive detection of bladder cancer. Subsequent preclinical validation confirmed the diagnostic potential of GHSR/MAL. These findings underline the diagnostic potential of the marker panel GHSR/MAL for future bladder cancer diagnostics.

Biochemical recurrence of prostate cancer (PCa) after curative radiotherapy is defined as a prostate-specific antigen (PSA) rise of ≥2 ng/ml above the nadir ("Phoenix criteria", 2005). With the introduction of prostate-specific membrane antigen positron emission tomography (PSMA-PET), the ability to localise PCa recurrences has increased markedly. Here, we reviewed 315 patients scanned with PSMA-PET after curative radiotherapy in the Prostate Cancer Network Amsterdam (2015-2018). Sixty-three patients (20.3%) were scanned below the Phoenix threshold (PSA rise

Item does not contain fulltext BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.

Background: In transgender men, effects of colpectomy on voiding function are unknown, except for the incidence rates of urinary tract infections and urinary retention. Aims: To provide insight into the effect of colpectomy on Lower Urinary Tract Function (LUTF) in transgender men. Methods: A retrospective chart review was conducted among transgender men who underwent colpectomy between January 2018 and October 2020. Primary outcomes were objective and subjective changes in voiding. Secondary outcomes were transurethral catheterization length and the need for clean intermittent self-catheterization (CISC). Results: Of 132 men, 89 (67%) underwent Robot-assisted Laparoscopic Colpectomy (RaLC) and 43 (33%) Vaginal Colpectomy (VC). Maximum flow rate on uroflowmetry decreased following RaLC (mean of 29.1 vs. 38.3 mL/s, p = 0.002) and VC (mean of 29.2 vs. 40.3 mL/s, p < 0.001) after a median of four months postoperatively. An increase in total International Prostate Symptom Score was seen more frequently following VC compared to RaLC. Subjective changes were indicated by 39%, more often by men who underwent VC, of which the majority improved during the first months postoperatively. Trial without catheter (TWOC) on the first postoperative day was more successful after RaLC (79/89, 89%) than VC (24/43, 56%). Secondary TWOC was successful in 22/132 (17%) patients after a median of eight days postoperatively. In 5/132 (4%) men (three VC and two RaLC), temporary CISC was necessary for a period ranging from 5 to 21 days. The last 2/132 (2%) men after RaLC were still performing CISC at end of follow-up. Eventually, 5% (two VC and four RaLC) had to refrain from genital gender-affirming surgery with urethral lengthening due to voiding dysfunction. Discussion: After colpectomy, most objective and subjective worsening in LUTF is of a temporary nature, however, 5% had to refrain from genital gender-affirming surgery with urethral lengthening due to persistent voiding dysfunction, despite the desire to void while standing.

SamenvattingHet doel van deze studie was te onderzoeken of de bevindingen op een 18F‑DCFPyL PET/CT-scan leiden tot een verandering van het behandeladvies voor patiënten met een biochemisch recidief (BCR) prostaatkanker. 253 patiënten met BCR-prostaatkanker bij wie een 18F‑DCFPyL PET/CT-scan werd gemaakt ter herstadiëring, werden geïncludeerd. Twee urologen formuleerden een voorgestelde behandeling voor elke patiënt voor- en nadat zij kennis hadden genomen van de uitslagen van de 18F‑DCFPyL PET/CT-scan. Bij 103/253 patiënten (40,7%) werd een verandering van het behandeladvies beschreven. Een positieve 18F‑DCFPyL PET/CT-scan (p p = 0,024) waren significante voorspellers van een voorgenomen beleidswijziging, terwijl een positieve chirurgische marge (p = 0,022) negatief geassocieerd was met een voorgenomen beleidswijziging. De conclusie luidt dat bevindingen op een 18F‑DCFPyL PET/CT-scan een significante impact hebben op het voorgestelde beleid bij patiënten met BCR-prostaatkanker.

SamenvattingHet doel van deze studie was om de rol van PSMA-PET/CT vast te stellen bij patiënten met biochemische persistentie (BCP) van prostaatkanker na robotgeassisteerde laparoscopische radicale prostatectomie (RALP). Geïncludeerd werden 150 patiënten met BCP na RALP, bij wie een PSMA-PET/CT-scan werd gemaakt. Een multivariabele logistische regressieanalyse werd uitgevoerd ter identificatie van voorspellers voor de detectie van metastasen buiten de prostaatloge (≥miN1) op PSMA-PET/CT. Bij 89/150 patiënten waren er aanwijzingen voor prostaatkanker buiten de prostaatloge (≥miN1). Een hogere PSA-waarde na RALP (p = 0,004) en een positieve pathologische lymfeklierstatus (p = 0,006) waren voorspellers voor PSMA-avide laesies buiten de prostaatloge. Het bleek dat bij een groot deel van de patiënten op de PSMA-PET/CT-scan met BCP na een RALP vanwege gelokaliseerd prostaatkanker, metastasen buiten de prostaatloge werden gezien. Hogere PSA-waarden en een positieve pathologische lymfeklierstatus waren significant geassocieerd met metastasen buiten de prostaatloge. De conclusie luidt dat bij patiënten met BCP een PSMA-PET/CT-scan is geïndiceerd om tot salvagebehandelbeslissingen te komen.

PURPOSE: Catheter-related bladder discomfort occurs in up to 63% of patients following robot-assisted radical prostatectomy. The optimal intraoperative anesthesia regime to prevent patients from catheter-related bladder discomfort is unknown.MATERIALS AND METHODS: A prospective cohort analysis was conducted. Patients with biopsy-proven prostate cancer selected for robot-assisted radical prostatectomy were included between January 2017 and April 2020 from a high volume prostate cancer center. Eight different treatment regimens were compared, ie a combination of general anesthesia and a transversus abdominis plane block with either an additional dose of clonidine or an additional dose of ketamine, or perivesical infiltrations (with 20 ml ropivacaine), or periurethral infiltrations (with ropivacaine); or a dorsal penile nerve block (with 20 ml ropivacaine). Multiple logistic regression and linear mixed models were used to analyze differences in catheter-related bladder discomfort and pain (0-10) at the postoperative recovery unit between the treatment protocols.RESULTS: Of the 391 patients included, those with a combination transversus abdominis plane block, perivesical and periurethral block with ropivacaine had the lowest incidence of catheter-related bladder discomfort, clinically relevant and statistically significantly lower compared to our baseline protocol (transversus abdominis plane block only), ie 36% vs 70%, p=0.001. Overall, patients who were treated with periurethral and/or perivesical infiltrations reported a statistically significantly lower incidence of catheter-related bladder discomfort compared to patients who did not receive this local infiltration (46.5% vs 60.7%, p=0.001).CONCLUSIONS: Perivesical and periurethral injections with ropivacaine have the potential to reduce the incidence of early postoperative catheter-related bladder discomfort by up to 49%. Further randomized studies are necessary to determine the optimal treatment regime to prevent early postoperative catheter-related bladder discomfort.

PURPOSE: We sought to identify a subset of patients in whom an extended pelvic lymph node dissection during robot-assisted laparoscopic radical prostatectomy for localized prostate cancer could be omitted when preoperative prostate specific membrane antigen positron emission tomography showed no lymph node metastatic prostate cancer. MATERIALS AND METHODS: A total of 434 patients who underwent prostate specific membrane antigen positron emission tomography prior to robot-assisted laparoscopic radical prostatectomy and extended pelvic lymph node dissection were retrospectively analyzed. Patients were excluded from analysis when the prostate specific membrane antigen positron emission tomography showed evidence of distant metastases. The primary outcome was whether a negative for metastases prostate specific membrane antigen positron emission tomography was able to correctly rule out pelvic lymp node metastases after extended pelvic lymph node dissection, ie its negative predictive value. RESULTS: Overall sensitivity, specificity, positive predictive value and negative predictive value of prostate specific membrane antigen positron emission tomography for the detection of pelvic lymp node metastases were 37.9%, 94.1%, 64.3% and 84.4%, respectively. The negative predictive value of prostate specific membrane antigen positron emission tomography in patients with intermediate risk prostate cancer was 91.6% (95% CI 86-97), compared to 81.4% (95% CI 77-86) in patients with high risk prostate cancer. When only assessing patients with

Cell-free DNA (cfDNA) can be isolated from blood and/or urine of cancer patients and analyzed with sequencing. Unfortunately, most conventional short-read sequencing methods are technically challenging, labor intensive and time consuming, requiring several days but more typically weeks to obtain interpretable data which are limited by a bias for short cfDNA fragments.Here, we demonstrate that with Oxford Nanopore Technologies sequencing we can achieve economical and ultra-fast delivery of clinical data from liquid biopsies.Our ‘ITSFASTR’ approach is able to deliver copy number aberrations, and cfDNA fragmentation profiles in less than 24 hours from sample collection. The tumorderived cfDNA fraction calculated from lung cancer patient plasma and urine from bladder cancer patients was highly correlated (R=0.98) to the tumor fraction calculated from conventional short-read sequencing of the same samples. cfDNA size profile and fragmentation patterns in plasma and urine exhibited the typical cfDNA features yet with a significantly higher proportion of fragments that exceed 300bp, exhibiting similar tumor fraction than shorter size fragments. Notably, comprehensive fragment-end composition and nucleosome profiling near transcription start sites can be determined from the same data.We propose that ITSFASTR is the first point-of-care solution for obtaining genomic and fragmentomic results from liquid biopsies.

Purpose The aim of this study was to investigate whether an early, accurate identification of disease using 18F-DCFPyL PET/CT imaging resulted in a change of decision on treatment management, for individual patients with biochemically recurrent (BCR), hormone-sensitive prostate cancer. Methods In this retrospective study, a total of 253 patients with BCR who underwent restaging 18F-DCFPyL PET/CT were assessed. Two urologists specialized in uro-oncology were asked to formulate a preferred treatment for each patient before and after knowing the results of the 18F-DCFPyL PET/CT. Results Out of 253 patients, 191 (75%) underwent robot-assisted radical prostatectomy (RARP) as primary therapy, and 62 (25%) external beam radiation therapy (EBRT). In 103/253 cases (40.7%), a preferred treatment change based on the 18F-DCFPyL PET/CT findings was reported. In patients post-RARP, a positive 18F-DCFPyL PET/CT (OR 6.21; 95%CI 2.78–13.8; p p = 0.024) were significant predictors for an intended change of management, whereas a positive surgical margin (OR 0.42; 95%CI 0.20–0.88; p = 0.022) was inversely associated with an intended change of management. Conclusion In this study, we found a significant impact of 18F-DCFPyL PET/CT on the intended management of patients with biochemically recurrent hormone-sensitive prostate cancer. A positive 18F-DCFPyL PET/CT scan, positive pathological lymph node status, and a negative surgical margin status were significantly associated with increased odds of having a change of management based on 18F-DCFPyL PET/CT findings.

Background Genital gender-affirming surgery (gGAS) with urethral lengthening (UL) in transgender men is associated with high urological complication and reoperation rates. Since 2009, we offer gGAS without UL to avoid these complications. Aim The aim of this study was to assess what portion of the transgender men opted for gGAS without UL and to assess functional, surgical outcomes, and patient satisfaction after gGAS without UL. Material and methods Retrospective data were collected from patients’ charts. The International Prostate Symptom Score, uroflowmetry, and 24-hour frequency voiding chart were used to assess voiding, and a self-constructed semistructured questionnaire was used to assess patient-reported outcomes. Transgender men who underwent gGAS without UL between January 2009 and January 2018 were included, and 56 transgender men were approached to complete the patient-reported outcome measurement. The simple statistical analysis combined with the Mann-Whitney U test and the Wilcoxon signed-rank test was used. Outcomes 68 transgender men were included. Median follow-up time was 24 (6–129) months. Uroflowmetry and the International Prostate Symptom Score were completed by 44 transgender men, whereas 13 completed the frequency voiding chart preoperatively and postoperatively, respectively. The patient-reported outcome measurement was completed by 40 of 56 (71%) transgender men. Result Postoperative surgical and urological complications occurred in 9 of 68 (13%) and 8 of 68 (12%) patients, respectively. Storage and voiding function remained unchanged. The median quality of life because of urinary symptoms was scored as “pleased.” Sexual functioning and voiding were scored satisfactory and very satisfactory in 18 of 40 (45%) and 21 of 40 (53%) patients, respectively. The number of patients satisfied with the penis and neoscrotum was 25 of 40 (63%) and 26 of 40 (65%), respectively. Increased self-esteem was reported by 32 of 40 (80%), 32 of 40 (80%) would undergo the surgery again, and 28 of 40 (70%) would recommend it to others. Clinical Implications gGAS without UL should be part of the surgical armamentarium in centers performing gender-affirming surgery. Strengths and limitations Strengths of this study comprise the number of patients, the completeness of data, incorporation of patient-reported outcomes, and description of a relatively new surgical approach that may be well-suitable for a subgroup of transgender men. Limitations are the retrospective study design and the lack of validated questionnaires. Conclusion gGAS without UL shows good surgical and urological outcomes. After extensive counseling, the majority of this selective group of patients shows favorable patient-reported outcomes.

The interpretation of conventional MRI may be limited by the two-dimensional presentation of the images. To develop patient-specific MRI prostate-based virtual and three-dimensional (3D)-printed models. To assess the association between 3D imaging and the pathological outcome of RARP specimen. To assess the clinical applicability of 3D models to guide nerve-sparing robot-assisted radical prostatectomy (RARP). We created virtual 3D and 3D-printed 3D models of 20 prostate cancer patients retrospectively. A comparison was made between conventional MRI and 3D-reconstructed images. The concordance between tumour lesion location in 3D models and pathology reporting of RARP specimens was assessed. Seven urologists assessed the side-specific extent of nerve-sparing based on (1) conventional MR images, (2) virtual 3D models, and (3) 3D-printed models. Clinically relevant changes in nerve-sparing and the absolute agreement between observers was analyzed using the Chi-square test and intra-class correlation coefficient (ICC). The index lesion was correctly visualized in 19/20 (95%) 3D models and the expected location of extraprostatic extension was correctly visualized in all 3D models. Clinically relevant changes in the planned extent of nerve-sparing between MRI and virtual 3D models and MRI and 3D-printed models were found in 25% and 26%. The ICC of the planned extent of nerve-sparing between urologists was 0.40 (95% CI 0.28-0.55) for conventional MRI, 0.52 (95% CI 0.39-0.66) for virtual 3D models and 0.58 (95% CI 0.45-0.71) for 3D-printed models. 3D models of the MRI prostate to guide RARP could aid urologists in the planning of nerve-sparing surgery as shown by a higher inter-observer agreement.

Purpose In primary prostate cancer (PCa) patients, accurate staging and histologic grading are crucial to guide treatment decisions. 18F-DCFPyL (PSMA)-PET/CT has been successfully introduced for (re)staging PCa, showing high accuracy to localise PCa in lymph nodes and/or osseous structures. The diagnostic performance of 18F-DCFPyL-PET/CT in localizing primary PCa within the prostate gland was assessed, allowing for PSMA-guided targeted-prostate biopsy. Methods Thirty patients with intermediate-/high-risk primary PCa were prospectively enrolled between May 2018 and May 2019 and underwent 18F-DCFPyL-PET/CT prior to robot-assisted radical prostatectomy (RARP). Two experienced and blinded nuclear medicine physicians assessed tumour localisation within the prostate gland on PET/CT, using a 12-segment mapping model of the prostate. The same model was used by a uro-pathologist for the RARP specimens. Based on PET/CT imaging, a potential biopsy recommendation was given per patient, based on the size and PET-intensity of the suspected PCa localisations. The biopsy recommendation was correlated to final histopathology in the RARP specimen. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for clinically significant PCa (csPCa, Gleason score ≥ 3 + 4 = 7) were assessed. Results The segments recommended for potential targeted biopsy harboured csPCA in 28/30 patients (93%), and covered the highest Gleason score PCa segment in 26/30 patient (87%). Overall, 122 of 420 segments (29.0%) contained csPCa at final histopathological examination. Sensitivity, specificity, PPV and NPV for csPCa per segment using 18F-DCFPyL-PET/CT were 61.4%, 88.3%, 68.1% and 84.8%, respectively. Conclusions When comparing the PCa-localisation on 18F-DCFPyL-PET/CT with the RARP specimens, an accurate per-patient detection (93%) and localisation of csPCa was found. Thus, 18F-DCFPyL-PET/CT potentially allows for accurate PSMA-targeted biopsy.

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas. (C) 2019 Elsevier Inc. All rights reserved.

Samenvatting177Lu-PSMA is een nieuwe, veelbelovende therapie bij patiënten met een gemetastaseerd castratieresistent prostaatcarcinoom (mCRPC). Het radioactief gelabelde medicijn wordt intraveneus toegediend in 1–6 cycli waarbij de β‑stralen zorgen voor intracellulaire DNA-schade en celdood van prostaatkankercellen met PSMA-expressie. Voornamelijk retrospectieve onderzoeken tonen aan dat het serum-PSA met ≥ 50 % daalt bij 40–60 % van deze vaak intensief behandelde patiëntengroep. Mogelijk is er een overlevingswinst in vergelijking met een niet-behandelde groep. De toxiciteit van 177Lu-PSMA is relatief gering. Er trad met name graad I–II CTCAE-xerostomie op bij 30–50 % van de patiënten, en veelal voorbijgaande graad III–IV CTCAE-hematologische toxiciteit (trombocytopenie, leukopenie) bij 0–15 %. De behandeling wordt momenteel onderzocht in meerdere prospectieve studies bij patiënten met mCRPC en in een gerandomiseerde studie. Het gebruik in vroegere fasen van prostaatkanker wordt geëvalueerd. Tot meer bekend is over de uitkomst van deze studies, blijft het gebruik van 177Lu-PSMA experimenteel.

BACKGROUND: Radical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited.OBJECTIVE: To assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice.METHODS AND MATERIALS: A nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status.RESULTS: The median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0-5.2). The median OS after ORC was 5.0 years (95%CI 4.3-5.6) versus 5.8 years after RARC (95%CI 5.1-6.5). The median RFS was 3.8 years (95%CI 3.1-4.5) after ORC versus 5.0 years after RARC (95%CI 3.9-6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84-1.20) and for RFS 1.08 (95%CI 0.91-1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage.CONCLUSION: ORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC.

The interpretation of conventional MRI may be limited by the two-dimensional presentation of the images. To develop patient-specific MRI prostate-based virtual and three-dimensional (3D)-printed models. To assess the association between 3D imaging and the pathological outcome of RARP specimen. To assess the clinical applicability of 3D models to guide nerve-sparing robot-assisted radical prostatectomy (RARP). We created virtual 3D and 3D-printed 3D models of 20 prostate cancer patients retrospectively. A comparison was made between conventional MRI and 3D-reconstructed images. The concordance between tumour lesion location in 3D models and pathology reporting of RARP specimens was assessed. Seven urologists assessed the side-specific extent of nerve-sparing based on (1) conventional MR images, (2) virtual 3D models, and (3) 3D-printed models. Clinically relevant changes in nerve-sparing and the absolute agreement between observers was analyzed using the Chi-square test and intra-class correlation coefficient (ICC). The index lesion was correctly visualized in 19/20 (95%) 3D models and the expected location of extraprostatic extension was correctly visualized in all 3D models. Clinically relevant changes in the planned extent of nerve-sparing between MRI and virtual 3D models and MRI and 3D-printed models were found in 25% and 26%. The ICC of the planned extent of nerve-sparing between urologists was 0.40 (95% CI 0.28–0.55) for conventional MRI, 0.52 (95% CI 0.39–0.66) for virtual 3D models and 0.58 (95% CI 0.45–0.71) for 3D-printed models. 3D models of the MRI prostate to guide RARP could aid urologists in the planning of nerve-sparing surgery as shown by a higher inter-observer agreement.

BACKGROUND: Bladder cancer imposes a significant public health burden on the European Union. There is a need for cost-effective treatment and follow-up regimens.OBJECTIVE: To assess the cost-effectiveness of immediate mitomycin C (MMC) instillation within 1 d after surgery compared to delayed MMC instillation within 2 wk after surgery with further adjuvant treatment, depending on the patient's risk group.DESIGN SETTING AND PARTICIPANTS: This economic evaluation was based on a randomized controlled trial among 2243 Dutch patients with non-muscle-invasive bladder cancer (NMIBC) patients from a health care perspective over a 3-yr time period.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The treatment effect was measured as time to recurrence and recurrence-free survival. Missing effect data were imputed with multiple imputation. Health care utilization and related costs were estimated on the basis of treatment protocols for NMIBC patients in the Netherlands. Statistical uncertainty was estimated using bootstrapping and is graphically presented using cost-effectiveness planes and cost-effectiveness acceptability curves.RESULTS AND LIMITATIONS: Time to recurrence was significantly longer for immediate MMC instillation (27.31 mo) than for delayed MMC instillation (24.97 mo), with an adjusted mean difference of 2.21 mo (95% confidence interval [CI] 1.58-2.84). The proportion of patients with recurrence-free survival was significantly higher after immediate MMC instillation (0.65) than after delayed MMC instillation (0.56), with an adjusted mean difference of 0.08 (95% CI 0.06-0.11). Total mean health care costs per patient were significantly lower for immediate MMC instillation (€22 959) than for delayed MMC instillation (€24 624), with an adjusted mean difference of -€1350 (95% CI -€1799 to -€900). The study is limited by the retrospective estimation of costs.CONCLUSIONS: This trial-based cost-effectiveness analysis shows that from a health care perspective, immediate MMC instillation is more effective and less expensive compared to delayed MMC instillation.PATIENT SUMMARY: We assessed the cost-effectiveness of immediate bladder instillation of mitomycin C after surgery to reduce the risk of recurrence after removal of the bladder tumor as compared to delayed instillation in a large Dutch population of patients with non-muscle-invasive bladder cancer. We found that immediate instillation was more effective and less expensive than delayed instillation. We conclude that immediate mitomycin C instillation is a cost-effective treatment for non-muscle-invasive bladder cancer.

We report a case of a successful treatment of post prostatectomy urinary stress incontinence with bulk injections after failed primary treatment with a sling. Keywords:Incontinence; Sling; Bulking agent; Therapy; Post-prostatectomy Case presentation A 70 year-old man was referred to theUrologen Kliniek Vleuten, with complaints of persistent stress urinary incontinence (SUI). His past medical history includes an open radical prostatectomy for a pT2cNxMx Gleason 6 adenocarcinoma of the prostate, with an initial PSA of 6.6 July 2011. Two years after prostatectomy the patient still complained of mild SUI, despite extensive pelvic floor physiotherapy. To treat the incontinence, an Argus sling was implanted in 2013. Nevertheless, the patient still complained of stress urinary incontinence after this procedure.

To optimize functional outcomes after robot-assisted radical prostatectomy (RARP), surgical preservation of the neurovascular bundle is desired. However, nerve-sparing surgery (NSS) is only feasible in the absence of extraprostatic tumour extension (T-stage 3) to avoid the risk of positive surgical margins (PSM). Multiparametric magnetic-resonance imaging (MRI) is increasingly performed for primary prostate cancer and provides information on local tumour stage. In this study, we evaluated whether the availability of information from MRI influenced the incidence of PSM. A total of 523 patients undergoing RARP for localized prostate cancer in a single Dutch reference centre for prostate-cancer surgery were retrospectively evaluated (2013–2017). Patient characteristics and postoperative outcomes were retrieved. Patients were stratified according to the presence of a preoperative MRI. The incidence of PSM and proportion of patients receiving NSS was analysed using Chi-square tests and logistic regression analysis. N = 139 of 523 (26.6%) patients had a preoperative MRI scan available. Patients with MRI had identical preoperative characteristics compared to the patients without MRI, except for a higher percentage of patients having a prostate-specific antigen value ≥ 20 ng/mL (20.1% versus 9.4%, p = 0.004). PSM were present in 107/384 (27.9%) patients without MRI compared to 36/139 (25.9%) patients with an MRI scan before surgery (p = 0.66). Unilateral NSS was performed more often in the MRI group (26.6% vs. 11.7%), but NSS on both sides was more frequently performed in patients without MRI (57.6% versus 69.8%) (p < 0.001). MRI was not associated with PSM in multivariate analysis (p = 0.265). Preoperative mpMRI imaging was not associated with lower rates of positive surgical margins in patients undergoing RARP for localized prostate cancer.

Background: In the current European Association of Urology (EAU) non-muscle invasive bladder cancer (NMIBC) guideline, two classification systems for grade are advocated: WHO1973 and WHO2004/2016. Objective: To compare the prognostic value of these WHO systems. Design, setting, and participants: Individual patient data for 5145 primary Ta/T1 NMIBC patients from 17 centers were collected between 1990 and 2019. The median follow-up was 3.9 yr. Outcome measurements and statistical analysis: Univariate and multivariable analyses of WHO1973 and WHO2004/2016 stratified by center were performed for time to recurrence, progression (primary endpoint), cystectomy, and duration of survival, taking into account age, concomitant carcinoma in situ, gender, multiplicity, tumor size, initial treatment, and tumor stage. Harrell's concordance (C-index) was used for prognostic accuracy of classification systems. Results and limitations: The median age was 68 yr; 3292 (64%) patients had Ta tumors. Neither classification system was prognostic for recurrence. For a four-tier combination of both WHO systems, progression at 5-yr follow-up was 1.4% in lowgrade (LG)/G1, 3.8% in LG/G2, 7.7% in high grade (HG)/G2, and 18.8% in HG/G3 (log rank, p < 0.001). In multivariable analyses with WHO1973 and WHO2004/2016 as independent variables, WHO1973 was a significant prognosticator of progression (p < 0.001), whereas WHO2004/2016 was not anymore (p = 0.067). C-indices for WHO1973, WHO2004, and the WHO systems combined for progression were 0.71, 0.67, and 0.73, respectively. Prognostic analyses for cystectomy and survival showed results similar to those for progression. Conclusions: In this large prognostic factor study, both classification systems were prognostic for progression but not for recurrence. For progression, the prognostic value of WHO1973 was higher than that of WHO 2004/2016. The four-tier combination (LG/G1, LG/G2, HG/G2, and HG/G3) of both WHO systems proved to be superior, as it divides G2 patients into two subgroups (LG and HG) with different prognoses. Hence, the current EAU-NMIBC guideline recommendation to use both WHO classification systems remains correct. Patient summary: At present, two classification systems are used in parallel to grade non-muscle-invasive bladder tumors. Our data on a large number of patients showed that the older classification system (WHO1973) performed better in terms of assessing progression than the more recent (WHO2004/2016) one. Nevertheless, we conclude that the current guideline recommendation for the use of both classification systems remains correct, since this has the advantage of dividing the large group of WHO1973 G2 patients into two subgroups (low and high grade) with different prognoses. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background: The European Association of Urology (EAU) prognostic factor risk groups for non–muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. Design, setting, and participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. Outcome measurements and statistical analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. Results and limitations: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004–2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from 40%. Limitations include the retrospective collection of data and the lack of central pathology review. Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. Patient summary: The newly updated European Association of Urology prognostic factor risk groups for non–muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule. The updated European Association of Urology prognostic factor risk groups for patients with non–muscle-invasive bladder cancer provide urologists with information that they should take into account when choosing a patient's treatment and scheduling follow-up.

PURPOSE: We assessed predictors of short-term oncologic outcomes of patients who underwent salvage radiation therapy for biochemical recurrence after robot-assisted laparoscopic radical prostatectomy without evidence of metastases on prostate specific membrane antigen positron emission tomography/computerized tomography. MATERIALS AND METHODS: We retrospectively analyzed 194 patients with biochemical recurrence after robot-assisted laparoscopic radical prostatectomy who underwent prostate specific membrane antigen positron emission tomography/computerized tomography prior to salvage radiation therapy. Patients with lymph node or distant metastases on restaging imaging or at the time of extended pelvic lymph node dissection during robot-assisted laparoscopic radical prostatectomy were excluded, as were patients who received androgen deprivation therapy during or prior to salvage radiation therapy. A multivariable logistic regression analysis was performed to assess predictors of treatment response, defined as prostate specific antigen value ≤0.1 ng/ml after salvage radiation therapy. RESULTS: Overall treatment response after salvage radiation therapy was 75% (146/194 patients). On multivariable analysis, prostate specific antigen value at initiation of salvage radiation therapy (OR 0.42, 95% CI 0.27-0.62, p

Purpose The detection of lymph-node metastases (N1) with conventional imaging such as magnetic resonance imaging (MRI) and computed tomography (CT) is inadequate for primarily diagnosed prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) PET/CT is successfully introduced for the staging of (biochemically) recurrent PCa. Besides the frequently used 68gallium-labelled PSMA tracers, 18fluorine-labelled PSMA tracers are available. This study examined the diagnostic accuracy of 18F-DCFPyL (PSMA) PET/CT for lymph-node staging in primary PCa. Methods This was a prospective, multicentre cohort study. Patients with primary PCa underwent 18F-DCFPyL PET/CT prior to robot-assisted radical prostatectomy (RARP) with extended pelvic lymph-node dissection (ePLND). Patients were included between October 2017 and January 2020. A Memorial Sloan Kettering Cancer Centre (MSKCC) nomogram risk probability of ≥ 8% of lymph-node metastases was set to perform ePLND. All images were reviewed by two experienced nuclear physicians, and were compared with post-operative histopathologic results. Results A total of 117 patients was analysed. Lymph-node metastases (N1) were histologically diagnosed in 17/117 patients (14.5%). The sensitivity, specificity, positive predictive value and negative predictive value for the 18F-DCFPyL PET/CT detection of pelvic lymph-node metastases on a patient level were 41.2% (confidence interval (CI): 19.4–66.5%), 94.0% (CI 86.9–97.5%), 53.8% (CI 26.1–79.6%) and 90.4% (CI 82.6–95.0%), respectively. Conclusion 18F-DCFPyL PET/CT showed a high specificity (94.4%), yet a limited sensitivity (41.2%) for the detection of pelvic lymph-node metastases in primary PCa. This implies that current PSMA PET/CT imaging cannot replace diagnostic ePLND. Further research is necessary to define the exact place of PSMA PET/CT imaging in the primary staging of PCa.

Simple Summary There is a clinical need for non-invasive methods to detect urogenital cancer, for which urine offers a promising liquid biopsy. Tumor DNA in urine originates from shedding of the local tumor, but may also be excreted transrenally as circulating DNA fragments from the bloodstream. To assess the origin of tumor-associated DNA in the urine of urogenital cancer patients, molecular tumor markers were tested in natural voided urine, and in urine samples in which contact with the local tumor was circumvented. The latter concerned nephrostomy urine of bladder cancer patients and catheter urine of cervical cancer patients. We demonstrated that tumor DNA in the urine of urogenital cancer patients results not only from the shedding of the local tumor, but also from transrenal excretion of circulating tumor DNA. This supports the great potential of urine as a diagnostic tool for cancer detection. Abstract In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

OBJECTIVES: To systematically summarise the available evidence on urinary bladder cancer (BC) mutation markers. Gene mutations are expected to provide novel biomarkers for urinary BC diagnosis. To date, evidence on urinary BC mutation markers has not proven sufficient to be adopted by clinical guidelines. In the present systematic review, diagnostic accuracy of urinary mutation analysis is separately assessed for primary BC diagnosis (BC detection) and for follow-up of BC patients (BC surveillance).METHODS: A literature search (PubMed, Embase.com and Wiley/Cochrane Library) and systematic review was performed up to 31 October 2019. As studies were too heterogeneous, no quantitative analysis could be performed.RESULTS: In total, 25 studies were summarised by qualitative analysis. For BC detection, diagnostic accuracy differed considerably for single mutation markers (sensitivity 1-85%, specificity 84-100%), and for marker panels (sensitivity 50-94%, specificity 43-97%). Similarly, for BC surveillance, diagnostic accuracy was highly variable for single mutation markers (sensitivity 0-85%, specificity 66-100%), and for marker panels (sensitivity 51-84%, specificity 66-96%).CONCLUSION: Urinary mutation analysis showed to be a promising diagnostic tool for non-invasive BC diagnosis. Nonetheless, we observed substantial differences in diagnostic accuracy of urinary BC mutation markers among publications. To translate the data summarised in the present review to future clinical practice, heterogeneity in research design, BC population, mutation analysis technique and urinary DNA should be considered. Eventual clinical implementation of urinary BC mutation markers can only be achieved by collecting more and stronger evidence. Combining different molecular assays might overcome current shortcomings of urinary mutation analysis.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events, including surgery, are discouraged as this is known to trigger a flare-up with risk of subsequent HO. Anesthetic management for patients with FOP is challenging. Cervical spine fusion, ankylosis of the temporomandibular joints, thoracic insufficiency syndrome, restrictive chest wall disease, and sensitivity to oral trauma complicate airway management and anesthesia and pose life-threatening risks. We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and N2O-inhalation were performed in this case. The surgery itself was securely planned to avoid any unnecessary tissue damage. Postoperatively the patient was closely monitored for FOP activity by ultrasound and [18F]PET/CT-scan. One year after surgery, a non-significant amount of HO had formed at the operated site. The systematic review revealed seventeen articles in which thirty-two limb surgeries in FOP patients were described. HO reoccurrence was described in 90% of the cases. Clinical improvement due to improved mobility of the operated joint was noted in 16% of the cases. It should be noted, though, that follow-up time was limited and no or inadequate imaging modalities were used to follow-up in the majority of these cases. To conclude, if medically urgent, limb surgery in FOP is possible even when general anesthesia is not preferred. The procedure should be well-planned, alternative techniques or procedures should be tested prior to surgery and special attention should be paid to the correct positioning of the patient. According to the literature recurrent HO should be expected after surgery of a limb, even though it was limited in the case described.

In the field of rare bone diseases in particular, a broad care team of specialists embedded in multidisciplinary clinical and research environment is essential to generate new therapeutic solutions and approaches to care. Collaboration among clinical and research departments within a University Medical Center is often difficult to establish, and may be hindered by competition and non-equivalent cooperation inherent in a hierarchical structure. Here we describe the “collaborative organizational model” of the Amsterdam Bone Center (ABC), which emerged from and benefited the rare bone disease team. This team is often confronted with pathologically complex and under-investigated diseases. We describe the benefits of this model that still guarantees the autonomy of each team member, but combines and focuses our collective expertise on a clear shared goal, enabling us to capture synergistic and innovative opportunities for the patient, while avoiding self-interest and possible harmful competition.

Context Therapies initiated by urologists, medical as well as surgical, may cause adverse effects in different sexual domains. Sexual domains that are often affected are sexual interest, sexual activity, and erectile functioning. As many elderly men undergo these therapies, it is important to know the prevalence of sexual dysfunction (SD) in these domains and its impact in the healthy elderly male population. This may help healthcare providers counsel their patients properly on possible adverse effects. Objective To review the prevalence of sexual functioning and SD in the domains of sexual desire, sexual activity, and erectile dysfunction (ED) and its impact (bother and medical use), stratified by age. Evidence acquisition This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Studies investigating the prevalence of SD, stratified by age, were eligible. Studies investigating bother due to ED, and studies evaluating medical use or use of medical professional healthcare providers in association with SD were eligible. Evidence synthesis A total of 76 articles were eligible for a full systematic review. Lack of sexual desire was reported to vary between 12% and 51.6% for men aged ≥60 yr, 20% and 65.9% for men aged ≥70 yr, and 40% and 82.4% for men aged ≥80 yr. The percentages of men bothered by ED were as follows: 14.3–70% for men aged ≥60 yr, 6.7–48% for men aged ≥70 yr, and 38% for men aged ≥80 yr. A substantial number of men (50.3–92%) find a normal sex life important as they age and remain sexually active. Only a minority of elderly men seek help from healthcare professionals or use medication for SD. Conclusions The prevalence of SD in the healthy male population, reflected by a loss of sexual desire and sexual activity, increases only slightly with age. Bother due to ED is relatively low and there is an association with age. Still, a large number of men in the middle-aged and elderly groups regard sexuality as an important aspect of life. While considering a surgical or medical therapy that could have an impact on sexual functioning, sexually related outcomes should be set against current sexual functioning and a probable decline of sexual functioning due to ageing. Patient summary While counselling elderly patients for sexual dysfunction when starting a treatment that could have an influence on sexual functioning, one should consider current sexual functioning and its importance for the individual.

Background For transgender men choosing to undergo phalloplasty with urethral lengthening, there is a potential for hair growth in the neourethra. Depilation of the urethral donor site may reduce subsequent intraurethral hair growth. Objectives To evaluate the effectiveness of preoperative laser depilation and assess the correlation between urethral hair density and voiding among transgender men undergoing phalloplasty with urethral lengthening. Design, setting, and participants This was a retrospective study of 25 transgender men undergoing phalloplasty with urethral lengthening between July 2010 and April 2015 at the VU University Medical Center in Amsterdam. Intervention Phalloplasty with urethral lengthening using skin with or without preoperative depilation. Outcome measurements and statistical analysis Data on preoperative laser depilation treatments were obtained from the local laser center. Intraurethral images were captured via urethroscopy and used to rate hair density. Images of the contralateral forearm were used as a reference. Hair density was rated in terms of the number of hairs per view as zero, low (1–9), moderate (10–19), or high (≥20). Voiding was assessed using the International Prostate Symptom Score (IPSS) questionnaire, a 24-h voiding diary, and uroflowmetry. Results and limitations Twenty-five patients underwent urethroscopy. In the depilation group (n = 14) the hair reduction was significant and hair density was downgraded on average by 1.0 points (95% confidence interval [CI] 0.5–1.5). The mean number of laser treatment sessions was 6 (range 2–10). In the no-depilation group (n = 11), hair density did not significantly differ between the urethra and the contralateral arm (mean difference 0.18, 95% CI 0.5–0.9). The majority of the patients reported mild voiding complaints (median IPSS score 7, range 2–28) and had a normal functional bladder capacity and a nonobstructed urinary flow with low postvoid volumes. Conclusions Laser epilation treatment reduces hair growth but does not eliminate hair. Voiding complaints do not seem to be related to hair density in the urethra. Patient summary For skin donor sites used in penis construction for transgender men, the amount of hair growth is reduced by preoperative laser depilation, but hair is still present in the new urethra. Hair in the urethra does not cause urinary voiding complaints.

Since the introduction of radiolabeled prostate-specific membrane antigen (PSMA) PET/CT, the ability to visualize recurrent prostate cancer has improved substantially. However, diagnostic accuracy is largely lacking for radiolabeled PSMA PET/CT in patients with biochemical persistence (BCP; that is, persistently measurable prostate-specific antigen [PSA] values after robot-assisted laparoscopic radical prostatectomy [RARP]). Therefore, the aim of this study was to determine the role of PSMA (i.e.,18F-DCFPyL or 68Ga-PSMA-11) PET/CT imaging in patients who experience BCP after RARP and to evaluate the sites of persistent disease on PSMA PET/CT. Methods: In total, 150 consecutive patients with BCP after RARP who underwent radiolabeled PSMA PET/CT imaging were retrospectively evaluated. BCP was defined as any detectable first serum PSA value after RARP (≥0.1 ng/mL) at least 6 wk after surgery, in the absence of an undetectable PSA value after RARP. A multivariable logistic regression analysis was performed to identify predictors for the detection of metastases outside the prostatic fossa (≥miN1) on PSMA PET/CT. Results: PSMA PET/CT was performed at a median PSA value of 0.60 ng/mL (interquartile range, 0.3-2.4) after a median of 6 mo (interquartile range, 4-10) after RARP. In total, 101 of 150 patients (67%) had lesions with PSMA expression on PET/CT, and 89 of 150 (59%) had lesions with increased PSMA expression sites outside the prostatic fossa. Moreover, 39 of 150 patients (26%) had PSMA-positive lesions outside the pelvis. On multivariable analysis, higher PSA values after RARP (P = 0.004) and positive pathologic lymph node status (P = 0.006) were independent predictors for ≥miN1. Conclusion: In the presence of BCP, a high proportion of patients already had disease metastatic to the pelvic lymph nodes or showed evidence of distant metastases, as indicated by PSMA PET/CT. Higher PSA levels after RARP and positive pathologic lymph node status were significantly associated with metastases outside the prostatic fossa. In patients with BCP, PSMA PET/CT imaging is warranted to guide salvage treatment strategies.