Management of the Devastated Bladder Outlet after Prostate CANCER Treatment.

PURPOSE OF REVIEW: Devastating complications of the bladder outlet resulting from prostate cancer treatments are relatively uncommon. However, the combination of the high incidence of prostate cancer and patient longevity after treatment have raised awareness of adverse outcomes deteriorating patients' quality of life. This narrative review discusses the diagnostic work-up and management options for bladder outlet obstruction resulting from prostate cancer treatments, including those that require urinary diversion. RECENT FINDINGS: The devastated bladder outlet can be a consequence of the treatment of benign conditions, but more frequently from complications of pelvic cancer treatments. Regardless of etiology, the initial treatment ladder involves endoluminal options such as dilation and direct vision internal urethrotomy, with or without intralesional injection of anti-fibrotic agents. If these conservative strategies fail, surgical reconstruction should be considered. Although surgical reconstruction provides the best prospect of durable success, reconstructive procedures are also associated with serious complications. In the worst circumstances, such as prior radiotherapy, failed reconstruction, devastated bladder outlet with end-stage bladders, or patient's severe comorbidities, reconstruction may neither be realistic nor justified. Urinary diversion with or without cystectomy may be the best option for these patients. Thorough patient counseling before treatment selection is of utmost importance. Outcomes and repercussions on quality of life vary extensively with management options. Meticulous preoperative diagnostic evaluation is paramount in selecting the right treatment strategy for each individual patient. The risk of bladder outlet obstruction, and its severest form, devastated bladder outlet, after treatment of prostate cancer is not negligible, especially following radiation. Management includes endoluminal treatment, open or robot-assisted laparoscopic reconstruction, and urinary diversion in the worst circumstances, with varying success rates.

The Association between Urine N-Glycome and Prognosis after Initial Therapy for Primary Prostate Cancer.

Next to prostate-specific antigen, no biochemical biomarkers have been implemented to guide patient follow-up after primary therapy for localized prostate cancer (PCa). We evaluated the prognostic potential of urine N-glycome in terms of event-free survival (EFS) in patients undergoing primary therapy for PCa. The prognostic features of the urine N-glycosylation profile at diagnosis, assessed in 77 PCa patients, were determined in terms of EFS next to standard clinical parameters. The majority of patients were diagnosed with International Society of Urological Pathology grade ≤ 3 (82%) T1-2 tumors (79%) and without pelvic lymph node invasion (96%). The patients underwent active surveillance (14%), robot-assisted laparoscopic prostatectomy (48%), or external beam radiotherapy (37%). Decreased ratios of biantennary core-fucosylation were noted in patients who developed an event, which was linked to a shorter EFS in both the intention-to-treat cohort and all subcohort analyses. Combining the urine N-glycan biomarker with the D'Amico Risk Classification for PCa resulted in an improved nomogram for patient classification after primary therapy. The rate of urine N-glycan biantennary core-fucosylation, typically linked to more aggressive disease status, is lower in patients who eventually developed an event following primary therapy and subsequently in patients with a worse EFS. The combination of urine N-glycan biomarkers together with clinical parameters could, therefore, improve the post-therapy follow-up of patients with PCa.

A unified strategy to focal brachytherapy incorporating transperineal biopsy, image fusion, and real-time implantation with and without rectal spacer simulated in prostate phantoms.

Purpose: To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer. Material and methods: Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (125I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer. Results: The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D2cc) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively. Conclusions: Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the non-spacer implants. Further validation of this concept is warranted in clinical trials.

Radical cystectomy or trimodality therapy for muscle-invasive bladder cancer: a qualitative study exploring patient priorities and counselling needs when making a treatment choice.

BACKGROUND: This study aims to explore the priorities and counselling needs of patients with muscle-invasive bladder cancer faced with a decision between radical cystectomy and trimodality therapy. METHODS: We performed a qualitative study according to the phenomenological approach. Sixteen muscle-invasive bladder cancer survivors who underwent radical cystectomy or trimodality therapy completed a semi-structured interview between May 2022 and February 2023. Patients were recruited via Ghent University Hospital and a patient organisation. Data were analysed with inductive thematic analysis by a multi-disciplinary team using an iterative approach and investigators' triangulation. RESULTS: Four main priorities determining the treatment decision were identified. (1) curing the disease; (2) health-related quality of life (physical, mental and social); (3) confidence in the treatment, which was mainly based on trust in the clinician; and (4) personal attributes. Trust in the clinician can be achieved by fulfilling the patient's information needs (accurate, complete, clear, impartial, personalised, realistic, and transparent information), ensuring accessibility of the clinician, and creating a clear and personalised treatment plan, involving patients to the extend they desire. Many patients considered a patient decision aid as a valuable asset in this process. CONCLUSION: Priorities vary between patients with muscle-invasive bladder cancer. Identifying individual priorities and offering personalised information about them is crucial for ensuring trust in the clinician and confidence in the treatment. Use of a patient decision aid can be beneficial in this process.

Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genotyping.

De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely collected tissue has hindered genomic stratification and precision oncology. Here, we leveraged a rare study of surgical intervention in 43 de novo metastatic prostate cancers to assess somatic genotypes across 607 synchronous primary and metastatic tissue regions plus circulating tumor DNA. Intra-prostate heterogeneity was pervasive and impacted clinically relevant genes, resulting in discordant genotypes between select primary restricted regions and synchronous metastases. Additional complexity was driven by polyclonal metastatic seeding from phylogenetically related primary populations. When simulating clinical practice relying on a single tissue region, genomic heterogeneity plus variable tumor fraction across samples caused inaccurate genotyping of dominant disease; however, pooling extracted DNA from multiple biopsy cores before sequencing can rescue misassigned somatic genotypes. Our results define the relationship between synchronous treatment-sensitive primary and metastatic lesions in men with de novo metastatic prostate cancer and provide a framework for implementing genomics-guided patient management.

Comparison of different estimated glomerular filtration rates for monitoring of kidney function in oncology patients.

Background: Tyrosine kinase inhibitors (TKIs) are associated with kidney function deterioration. A shift is ongoing towards glomerular filtration rate (GFR) equations based on other protein markers, such as cystatin C (CSTC) and ß-trace protein (BTP). We evaluated various GFR equations for monitoring of kidney function in actively treated oncology patients. Methods: We monitored 110 patients receiving a TKI. Blood and urine were collected during therapy. Serum analysis included creatinine (Cr), CSTC and BTP; for consequent GFR determination. Urine was analysed for protein, albumin, immunoglobulin G, and α-1-microglobulin. A similar analysis was done in a patient subgroup receiving immune checkpoint inhibitors (ICI) as prior or subsequent line of therapy. Results: Cr remained constant during TKI treatment (P = 0.7753), whereas a significant decrease in CSTC (from week 2 onward, P < 0.0001) and BTP (at weeks 2 and 4, P = 0.0100) were noticed. Consequently, GFR estimations, using CSTC and/or BTP as a biochemical parameter, showed an apparent increase in GFR, whereas this was not observed for Cr-related GFR estimations. As a result, the GFR gap (ΔGFR) was significantly different from week 2 onward between Cr-based and CSTC-based GFR and between BTP-based and CSTC-based GFR. Glomerular damage was noticed with significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio and immunoglobulin G (all P < 0.0001). No change in α-1-microglobulin was seen. ICI treatment had no effect on Cr (P = 0.2262), CSTC (P = 0.7341), and BTP concentrations (P = 0.3592). Conclusion: GFR equations, in which CSTC is incorporated, fail to correctly estimate the GFR in oncology patients treated with TKIs. As TKI-treated patients show clear signs of glomerular injury, further assessment is needed on how to correctly monitor the kidney function in actively treated oncology patients.

Clinical Application of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation Score for Reporting Magnetic Resonance Imaging in Men on Active Surveillance for Prostate Cancer.

Background: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) score has been developed to standardise prostate magnetic resonance imaging (MRI) reporting in men on active surveillance (AS) for prostate cancer (PCa). Objective: To evaluate the feasibility of PRECISE scoring and assess its diagnostic accuracy. Design setting and participants: All PCa patients on AS with a baseline MRI and at least one follow-up MRI scan between January 2008 and September 2022 at a single tertiary referral centre were included in a database. The follow-up protocol of the Prostate Cancer International Active Surveillance (PRIAS) study was used. All scans were retrospectively re-reported by a dedicated uroradiologist and appointed a Prostate Imaging Reporting and Data System (version 2.1) and PRECISE score. Outcome measurements and statistical analysis: Clinically significant progression was defined by histopathological upgrading (on biopsy or radical prostatectomy) to grade group ≥3 and/or evolution to T3 stage. A survival analysis was performed to assess differential progression-free survival (PFS) according to the PRECISE score. Results and limitations: A total of 188 patients were included for an analysis with a total of 358 repeat MRI scans and 144 repeat biopsies. The median follow-up was 46 mo (interquartile range 21-74). Radiological progression (PRECISE 4-5) had sensitivity, specificity, negative predictive value, and positive predictive value of, respectively, 78%, 70%, 90%, and 49% for clinically significant progression. Four-year PFS was 91% for PRECISE 1-3 versus 66% for PRECISE 4-5 (p < 0.001). In total, 137 patients underwent a confirmation MRI scan within 18 mo after diagnosis. Four-year PFS in this group was 81% for PRECISE 1-3 versus 43% for PRECISE 4-5 (p < 0.001). Limitations include retrospective design and no strict adherence to AS protocol. Conclusions: Implementation of PRECISE scoring for PCa patients on AS is feasible and offers a prognostic value. Patients with PRECISE score 4-5 on confirmation MRI within 18 mo after diagnosis have a three-fold higher risk of clinically significant progression after 4 yr. Patient summary: Patients with low-risk prostate cancer can be followed up carefully. In this study, we evaluate the standardised reporting of repeat magnetic resonance imaging scans (using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation [PRECISE] recommendations). PRECISE scoring is feasible and helps identify patients in need of further treatment.

Whole Slide Imaging-Based Prediction of TP53 Mutations Identifies an Aggressive Disease Phenotype in Prostate Cancer.

In prostate cancer, there is an urgent need for objective prognostic biomarkers that identify the metastatic potential of a tumor at an early stage. While recent analyses indicated TP53 mutations as candidate biomarkers, molecular profiling in a clinical setting is complicated by tumor heterogeneity. Deep learning models that predict the spatial presence of TP53 mutations in whole slide images (WSI) offer the potential to mitigate this issue. To assess the potential of WSIs as proxies for spatially resolved profiling and as biomarkers for aggressive disease, we developed TiDo, a deep learning model that achieves state-of-the-art performance in predicting TP53 mutations from WSIs of primary prostate tumors. In an independent multifocal cohort, the model showed successful generalization at both the patient and lesion level. Analysis of model predictions revealed that false positive (FP) predictions could at least partially be explained by TP53 deletions, suggesting that some FP carry an alteration that leads to the same histological phenotype as TP53 mutations. Comparative expression and histologic cell type analyses identified a TP53-like cellular phenotype triggered by expression of pathways affecting stromal composition. Together, these findings indicate that WSI-based models might not be able to perfectly predict the spatial presence of individual TP53 mutations but they have the potential to elucidate the prognosis of a tumor by depicting a downstream phenotype associated with aggressive disease biomarkers. SIGNIFICANCE: Deep learning models predicting TP53 mutations from whole slide images of prostate cancer capture histologic phenotypes associated with stromal composition, lymph node metastasis, and biochemical recurrence, indicating their potential as in silico prognostic biomarkers. See related commentary by Bordeleau, p. 2809.

Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer.

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.

Benchmarking blood collection tubes and processing intervals for extracellular vesicle performance metrics.

The analysis of extracellular vesicles (EV) in blood samples is under intense investigation and holds the potential to deliver clinically meaningful biomarkers for health and disease. Technical variation must be minimized to confidently assess EV-associated biomarkers, but the impact of pre-analytics on EV characteristics in blood samples remains minimally explored. We present the results from the first large-scale EV Blood Benchmarking (EVBB) study in which we systematically compared 11 blood collection tubes (BCT; six preservation and five non-preservation) and three blood processing intervals (BPI; 1, 8 and 72 h) on defined performance metrics (n = 9). The EVBB study identifies a significant impact of multiple BCT and BPI on a diverse set of metrics reflecting blood sample quality, ex-vivo generation of blood-cell derived EV, EV recovery and EV-associated molecular signatures. The results assist the informed selection of the optimal BCT and BPI for EV analysis. The proposed metrics serve as a framework to guide future research on pre-analytics and further support methodological standardization of EV studies.

Is a Course of Intermittent Self-dilatation with Topical Corticosteroids Superior at Stabilising Urethral Stricture Disease in Men and Improving Functional Outcomes over a Course of Intermittent Self-dilatation Alone? A Systematic Review and Meta-analysis.

Context: Intermittent self-dilatation (ISD) is a therapeutic strategy used to stabilise a urethral stricture and postpone or avoid further treatment. Adding corticosteroids to this mode of management might further enhance its outcomes by downregulation of collagen deposition and excessive scar tissue formation. Objective: To explore whether a course of ISD with topical corticosteroids is superior at stabilising urethral stricture disease in men and improving functional outcomes over a course of ISD alone. Evidence acquisition: This systematic review and meta-analysis was undertaken by the European Association of Urology Urethral Strictures Guideline Panel according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (CRD42021256744). The primary benefit outcome was successful stabilisation of the urethral stricture. Treatment-related complications were the primary harm outcome. Evidence synthesis: In total, 978 records were screened for eligibility, ultimately leading to five included studies, all randomised controlled trials, comprising 250 patients, of whom 124 underwent a course of ISD with corticosteroids and 126 underwent a course of ISD alone, all after direct vision internal urethrotomy (DVIU). Successful stabilisation of the stricture was achieved in 77% and 64% of patients in the group with and without corticosteroids, respectively (p = 0.04). No extra complications related to the addition of corticosteroids to the ISD regimen were reported. The risk of bias of the included studies was generally unclear to high. Conclusions: Based on the currently available data, a course of ISD with topical corticosteroids appears to be safe and superior at stabilising a urethral stricture after DVIU in the short term to a course of ISD alone. However, given the unclear to high risk of bias in the included studies, further high-quality studies are needed to fully underpin this. Patient summary: This study shows that addition of topical corticosteroids to intermittent self-dilatation after direct vision internal urethrotomy can better stabilise the stricture in the short term.

Is It Safe to Switch from a Standard Anterior to Retzius-Sparing Approach in Robot-Assisted Radical Prostatectomy?

BACKGROUND: Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has been shown to lead to better outcomes regarding early continence compared to standard anterior RARP (SA-RARP). The goal of this study was to assess the feasibility and safety of implementing RS-RARP in a tertiary center with experience in SA-RARP. METHODS: From February 2020, all newly diagnosed non-metastatic prostate cancer patients for whom RARP was indicated were evaluated for RS-RARP. Data from the first 100 RS-RARP patients were prospectively collected and compared with data from the last 100 SA-RARP patients. Patients were evaluated for Clavien Dindo grade ≥3a complications, urinary continence after 2 and 6 weeks, 3, 6 and 12 months, erectile function, positive surgical margins (PSMs) and biochemical recurrence (BCR). RESULTS: There was no significant difference in postoperative complications at Clavien-Dindo grade ≥3a (SA-RARP: 6, RS-RARP: 4; p = 0.292). At all time points, significantly higher proportions of RS-RARP patients were continent (p < 0.001). No significant differences in postoperative potency were observed (52% vs. 59%, respectively, p = 0.608). PSMs were more frequent in the RS-RARP group (43% vs. 29%, p = 0.034), especially in locally advanced tumors (pT3: 64.6% vs. 43.8%, p = 0.041-pT2: 23.5% vs. 15.4%, p = 0.329). The one-year BCR-free survival was 82.6% vs. 81.6% in the SA-RARP and RS-RARP groups, respectively (p = 0.567). The median follow-up was 22 [18-27] vs. 24.5 [17-35] months in the RS-RARP and SA-RARP groups, respectively (p = 0.008). CONCLUSIONS: The transition from SA-RARP to RS-RARP can be safely performed by surgeons proficient in SA-RARP. Continence results after RS-RARP were significantly better at any time point. A higher proportion of PSMs was observed, although it did not result in a worse BCR-free survival.

Experiences of Men With Prostate Cancer Participating in a Clinical Pathway With a Supervised Group-based Exercise Program to Combat Androgen Deprivation-Induced Side Effects: A Qualitative Focus Group Study.

OBJECTIVES: A clinical pathway in daily practice improved implementation of evidence-based strategies for the management of androgen deprivation-induced side effects in men with prostate cancer. This study aimed to explore patients' expectations and reasons to start with the clinical pathway; explore patients' experiences and attitudes toward the pathway; and identify key pathway ingredients and examine patients' attitudes about a possible transition toward the home environment after a hospital-based pathway participation. DATA SOURCES: Focus group interviews were conducted through purposeful sampling, consisting of former and current participants of the clinical pathway at Ghent University Hospital. Data was audiotaped and transcribed verbatim, coded in NVivo12, and thematically and inductively analyzed through constant comparisons. CONCLUSION: Men with prostate cancer have positive experiences toward the use of a holistic multidisciplinary approach (ie, clinical pathway) to combat androgen deprivation therapy-induced side effects in practice. Patients identified several key ingredients of the pathway, such as peer support, physiotherapist involvement, and availability of a multidisciplinary team. Patients were, however, reluctant to continue the exercise component at home because of negative attitudes toward a public gym, practical issues, absence of known facilitators, and other priorities. IMPLICATIONS FOR NURSING PRACTICE: Referral by a health care provider remains an important motivator for pathway participation. Peer support, physiotherapist involvement, and availability of a multidisciplinary team are crucial components of the clinical pathway and should be taken into account when developing and implementing similar pathways to increase program uptake in daily practice.

Mapping European Association of Urology Guideline Practice Across Europe: An Audit of Androgen Deprivation Therapy Use Before Prostate Cancer Surgery in 6598 Cases in 187 Hospitals Across 31 European Countries.

BACKGROUND: Evidence-practice gaps exist in urology. We previously surveyed European Association of Urology (EAU) guidelines for strong recommendations underpinned by high-certainty evidence that impact patient experience for which practice variations were suspected. The recommendation "Do not offer neoadjuvant androgen deprivation therapy (ADT) before surgery for patients with prostate cancer" was prioritised for further investigation. ADT before surgery is neither clinically effective nor cost effective and has serious side effects. The first step in improving implementation problems is to understand their extent. A clear picture of practice regarding ADT before surgery across Europe is not available. OBJECTIVE: To assess current ADT use before prostate cancer surgery in Europe. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cross-sectional study. We retrospectively audited recent ADT practices in a multicentre international setting. We used nonprobability purposive sampling, aiming for breadth in terms of low- versus high-volume, academic, versus community and public versus private centres. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome was adherence to the ADT recommendation. Descriptive statistics and a multilevel model were used to investigate differences between countries across different factors (volume, centre type, and funding type). Subgroup analyses were performed for patients with low, intermediate, and high risk, and for those with locally advanced prostate cancer. We also collected reasons for nonadherence. RESULTS AND LIMITATIONS: We included 6598 patients with prostate cancer from 187 hospitals in 31 countries from January 1, 2017 to May 1, 2020. Overall, nonadherence was 2%, (range 0-32%). Most of the variability was found in the high-risk subgroup, for which nonadherence was 4% (range 0-43%). Reasons for nonadherence included attempts to improve oncological outcomes or preoperative tumour parameters; attempts to control the cancer because of long waiting lists; and patient preference (changing one's mind from radiotherapy to surgery after neoadjuvant ADT had commenced or feeling that the side effects were intolerable). Although we purposively sampled for variety within countries (public/private, academic/community, high/low-volume), a selection bias toward centres with awareness of guidelines is possible, so adherence rates may be overestimated. CONCLUSIONS: EAU guidelines recommend against ADT use before prostate cancer surgery, yet some guideline-discordant ADT use remains at the cost of patient experience and an additional payer and provider burden. Strategies towards discontinuation of inappropriate preoperative ADT use should be pursued. PATIENT SUMMARY: Androgen deprivation therapy (ADT) is sometimes used in men with prostate cancer who will not benefit from it. ADT causes side effects such as weight gain and emotional changes and increases the risk of cardiovascular disease, diabetes, and osteoporosis. Guidelines strongly recommend that men opting for surgery should not receive ADT, but it is unclear how well the guidance is followed. We asked urologists across Europe how patients in their institutions were treated over the past few years. Most do not use ADT before surgery, but this still happens in some places. More research is needed to help doctors to stop using ADT in patients who will not benefit from it.

The Changing Landscape of Systemic Therapy in the Treatment of Synchronous Metastatic Hormone-sensitive Prostate Cancer.

INTRODUCTION: To describe the changes in systemic treatments (ST) of synchronous metastatic hormone-sensitive prostate cancer (mHSPC) patients in a "real-world" setting and to explore reasons why contemporary standard of care (SOC) was not administrated to the patient. PATIENTS AND METHODS: Since 2014, we prospectively register mHSPCpatients. Patients were grouped in 4 time periods: group 1 (Time period 1, January 2014-July 2015), group 2 after introduction of docetaxel (Time period 2, August 2015-July 2017), group 3 after introduction of abiraterone acetate (Time period 3, August 2017-February 2018) and group 4 after introduction of apalutamide (Time period 4, March 2018-October 2021). For every time period, we evaluated the initiated additional ST. In case patients received treatment that differed from contemporary SOC according to guidelines, reasons for this difference were explored. RESULTS: In total, 243 patients were included. A progressive decline in ADT monotherapy from 85% to 29% over time was observed. The proportion of patients receiving additional STs increased from 34% to 59%. Forty percent of patients were not treated according to contemporary SOC, but this percentage varied strongly per time period (10%, 67%, 53%, and 32% from time period 1 to time period 4 respectively). Reasons for these variations were heterogenous and varied across the 4 time periods. Patients being unfit for treatment and treating physicians failing to consider additional STs were the most prevalent reasons. The proportion of patients unfit for additional ST decreased from 18% to 4% over time. CONCLUSION: Use of ADT monotherapy declined gradually after the introduction of additional systemic treatments. The proportion of patients unfit for additional ST declined as more treatments became available. Although compliance to SOC increased over time, these real-world data show that adherence to clinical practice guidelines remains suboptimal. Efforts should be made by clinicians to increase the adherence to practice guidelines.

The self-assessment of genital anatomy, sexual function, and genital sensation (SAGASF-M) questionnaire in a Belgian Dutch-speaking male population: A validating study.

INTRODUCTION: Penile and genital surgery for congenital or acquired conditions is daily practice in reconstructive urology. These procedures, which carry the risk of disrupting nerves and blood vessels, may impair the genital sensation, and affect the capacity for sexual pleasure. Self-reported tools are needed to systematically assess the male genitalia before and after reconstructive surgeries in terms of genital sensation and sexual experience. AIM: This study validated the Dutch translation of the "self-assessment of genital anatomy and sexual functioning in male" (SAGASF-M) questionnaire and investigated the perceptions of healthy men regarding their genital anatomy and sensory function. METHODS: Eight hundred and eight sexually active men with a median age of 39 years (18-79 years) and no history of genital procedures other than circumcision filled out an online version of the questionnaire. Twenty-four participants were randomly recruited to confirm the responses of the "self-assessment of genital anatomy and sexual functioning in male" questionnaire by a clinical evaluation. MAIN OUTCOME MEASURES: The "self-assessment of genital anatomy and sexual functioning in male" questionnaire comprises of multiple-choice questions and clarifying illustrations asking men to rate their genital appearance, overall sexual sensitivity, and pain perception as well as the intensity and the effort to reach orgasm. Prespecified regions of the glans, penile shaft, scrotum, perineum, and anus are evaluated through this questionnaire. RESULTS: Only slight variability in anatomical ratings was observed. Overall discrimination between different genital areas in terms of genital sensation was significant. The bottom of the glans or frenular area was rated the highest contributor to "sexual pleasure," followed by the other regions of the glans and shaft. The same distribution was found for "orgasm intensity" and "orgasm effort." The anal region was generally rated the lowest. "Discomfort/pain" was rated lower than any of the other sensory function indicators and the top of the glans and anal region were rated most likely to perceive this unpleasant sensation. Participants reported significantly more sexual pleasure and intense orgasms when stimulated by a sexual partner than self-stimulation. Homosexual and bisexual men reported a higher contribution of the perineal and anal regions in sexual pleasure and orgasm. No significant difference between circumcised and uncircumcised individuals regarding overall genital sensation could be found. CONCLUSION: The Dutch translation of the SAGASF-M questionnaire is a valuable and reliable tool for self-assessment of genital anatomy and sensation, providing a site-specific attribution of a patient's perceived sexual function. Further prospective research with this questionnaire could aid in the patient-centered improvement of genital surgery.

Vulvar pagetoid urothelial intraepithelial neoplasia: a case report.

BACKGROUND: Pagetoid urothelial intraepithelial neoplasia (PUIN) is a form of secondary Extramammary Paget Disease (EMPD). It is a rare malignant condition seen on the female genitalia synchronous or metachronous with bladder cancer (BC). CASE PRESENTATION: A 66-year-old female presented with PUIN at the labia minora 2 years after an open anterior pelvic exenteration with ileal conduit urinary diversion for carcinoma in situ (CIS) of the bladder. PUIN of the vulva and vagina was confirmed by a punch biopsy and the patient underwent a radical vaginectomy with urethrectomy and inguinal sentinel node procedure. Immunohistochemically EMPD was identified by the expression tumor protein 63 (p63), cytokeratin 7, and cytokeratin 20 (CK20). CONCLUSIONS: PUIN is a rare but distinct clinical entity as a form of secondary EMPD which can be differentiated from primary EMPD based on medical history, histology, and immunohistochemistry.

Evaluating the Impact of Prostate Only Versus Pelvic Radiotherapy for Pathological Node-positive Prostate Cancer: First Results from the Multicenter Phase 3 PROPER Trial.

BACKGROUND: The optimal treatment for patients with pathological node-positive (pN1) prostate cancer (PCa) is unclear. OBJECTIVE: To evaluate whether whole-pelvis radiotherapy (WPRT) improves clinical relapse-free survival (cRFS) in comparison to prostate-only radiotherapy (PORT) in pN1 PCa. DESIGN, SETTING, AND PARTICIPANTS: PROPER was a phase 3 trial randomizing patients to WPRT or PORT. All patients had pN1cM0 PCa with fewer than five lymph nodes involved. INTERVENTION: All patients underwent pelvic lymph node dissection followed by radical prostatectomy/primary radiotherapy + 2 yr of androgen deprivation therapy (ADT). Patients were randomized to PORT (arm A) or WPRT (arm B). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was cRFS. The secondary endpoints were overall survival (OS), biochemical relapse-free survival (bRFS), and toxicity. The study was stopped because of poor accrual in June 2021 after the inclusion of 69 patients. We report on OS, bRFS, cRFS, and acute and late toxicity. RESULTS AND LIMITATIONS: The median follow-up was 30 mo in arm A (n = 33) and 36 mo in arm B (n = 31). The 3-yr OS rate was 92% ± 5% in arm A and 93% ± 5% in arm B (p = 0.61). None of the patients died of PCa. The 3-yr bRFS was 79% ± 9% in arm A and 92% ± 5% in arm B (p = 0.08). The 3-yr cRFS rate was 88% ± 6% in arm A and 92% ± 5% in arm B (p = 0.31). No pelvic recurrence was observed in arm B. Acute grade 2 gastrointestinal toxicity was higher with WPRT (15% in arm A vs 45% in arm B; p = 0.03). Limitations are the early closure because of poor accrual and the limited follow-up. CONCLUSIONS: The results of our trial are hypothesis-generating but add evidence supporting the recommendation to offer WPRT to patients with pN1 PCa. However, WPRT is associated with more acute gastrointestinal toxicity. PATIENT SUMMARY: We looked at the impact of radiotherapy to the whole pelvis (WPRT) for patients with prostate cancer that had spread to the lymph nodes. Although the trial was closed early because of poor enrolment, we found that WPRT improves survival free from relapse, and no recurrences were observed in the pelvis. WPRT is associated with more acute side effects on the gastrointestinal system in comparison to radiotherapy to just the prostate.

Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

Retzius-Sparing Robot-Assisted Radical Prostatectomy.

The technique of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) and initial experience with it at a single center are provided. The technique is described step-by-step and further illustrated by a video to enhance reproducibility. Early oncological and functional results were evaluated. In total, 77 patients were included with a median follow-up of 11 months (range: 3-21 months). Fifty-one percent of patients had local high-risk or locally advanced prostate cancer. There were no intra-operative complications, and all high-grade complications (2.6%) were related to pelvic lymph node dissection performed concomitant with RS-RARP. Median operation time was 160 min (range: 122-265 min) and median hospital stay was 3 (range: 3-8) days. A positive surgical margin was reported in 42.9%. One-year biochemical recurrence-free survival was 90.1%. After 6 months, all patients were socially continent and after 1 year, 94.3% were fully continent. Of sexually active patients who underwent at least unilateral nerve-sparing, 43.3% were able to have sexual intercourse. This series underlines the surgical safety of performing RS-RARP by a standardized technique and confirms the beneficial effect on the early return of continence. The patient needs to be informed about the risk of a positive surgical margin.