Surveillance of non-muscle-invasive bladder cancer with blue-light cystoscopy: a meta-analysis.

OBJECTIVE: To compare the value of flexible blue-light cystoscopy (BLC) vs flexible white-light cystoscopy (WLC) in the surveillance setting of non-muscle-invasive bladder cancer (NMIBC). METHODS: All major databases were searched for articles published before May 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the accuracy of flexible BLC vs WLC in detecting bladder cancer recurrence among suspicious bladder lesions. RESULTS: A total of 10 articles, comprising 1634 patients, were deemed eligible for the quantitative synthesis. In the meta-analysis focusing on the detection of disease recurrence, there was no difference between flexible BLC and WLC (odds ratio [OR] 1.08, 95% confidence interval [CI] 0.82-1.41)]; the risk difference (RD) showed 1% of flexible BLC, corresponding to a number needed to treat (NNT) of 100. In the subgroup meta-analysis of detection of carcinoma in situ (CIS) only, there was again no significant difference between flexible BLC and WLC (OR 1.19, 95% CI 0.82-1.69), BLC was associated with a RD of 2% (NNT = 50). The positive predictive values for flexible BLC and WLC in detecting all types of recurrence were 72% and 66%, respectively, and for CIS they were 39% and 29%, respectively. CONCLUSION: Surveillance of NMIBC with flexible BLC could detect more suspicious lesions and consequently more tumour recurrences compared to flexible WLC, with a increase in the rate of false positives leading to overtreatment. A total of 100 and 50 flexible BLC procedures would need to be performed to find on additional tumor and CIS recurences, respectively. A risk-stratified strategy for patient selection could be considered when using flexible BLC for the surveillance of NMIBC patients.

[Large Language Models for Rapid Simplification of Quality Assurance Data Input: Field Trial with Real Data in the Context of Tumour Documentation in Urology]. / Large Language Modelle zur schnellen Vereinfachung der Eingabe von Qualitätssicherungsdaten: Performance-Test mit Echtdaten am Beispiel der Tumordokumentation in der Urologie.

INTRODUCTION: Large Language Models (LLMs) such as ChatGPT have rapidly brought the application of artificial intelligence into widespread use. Among many different use cases for text generation and processing, one application is the extraction of data from existing documents and conversations for simplified and automated form-filling. OBJECTIVE: In the field of quality assurance and documentation of cancer diseases, there is currently a significant workload involved in transferring data under various aspects into slightly varying formats and applying interpretations such as the TNM classification of tumours. However, there is a lack of trials with real data to assess the applicability of LLM-supported processes in this area, which would enable an evaluation of efficiency and practicality. This study aims to implement and assess such a trial. METHODOLOGY: A trial was conducted with N=153 privacy-compliant and ethics committee-cleared medical reports from 25 patients. Using the publicly available version of ChatGPT 4.0, an automated script was used to extract the date of initial diagnosis and common tumor classifications. The results were then individually checked for accuracy. Based on this, the utility of a simple system for guided support in tasks related to tumour documentation was assessed. Additionally, the approach was evaluated in terms of operational costs for the model and its applicability. RESULTS: In summary, the study concludes that the use of generative AI in this field is promising and suitable as a tool even in an untrained state. In a simplified calculation, costs of 35 cents are offset by a value creation of 61,54 euros. However, it also becomes clear that AI can only act in a supportive role, and the correct integration with pre-made specific prompts and tools into the workflow is crucial for a relevant performance. CONCLUSION: The use of generative AI in the context of search, transfer, and interpretation tasks in the creation of tumor documentation is a promising approach. However, its implementation in practical applications must be closely monitored, and the optimal interaction between man and machine should continue to be evaluated and must be accompanied by tools and task-specific prompts.

Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

Targeting cancer-derived extracellular vesicles by combining CD147 inhibition with tissue factor pathway inhibitor for the management of urothelial cancer cells.

BACKGROUND: Extracellular vesicles (EVs), including microvesicles, hold promise for the management of bladder urothelial carcinoma (BLCA), particularly because of their utility in identifying therapeutic targets and their diagnostic potential using easily accessible urine samples. Among the transmembrane glycoproteins highly enriched in cancer-derived EVs, tissue factor (TF) and CD147 have been implicated in promoting tumor progression. In this in vitro study, we explored a novel approach to impede cancer cell migration and metastasis by simultaneously targeting these molecules on urothelial cancer-derived EVs. METHODS: Cell culture supernatants from invasive and non-invasive bladder cancer cell lines and urine samples from patients with BLCA were collected. Large, microvesicle-like EVs were isolated using sequential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and flow cytometry. The impact of urinary or cell supernatant-derived EVs on cellular phenotypes was evaluated using cell-based assays following combined treatment with a specific CD147 inhibitor alone or in combination with a tissue factor pathway inhibitor (TFPI), an endogenous anticoagulant protein that can be released by low-molecular-weight heparins. RESULTS: We observed that EVs obtained from the urine samples of patients with muscle-invasive BLCA and from the aggressive bladder cancer cell line J82 exhibited higher TF activity and CD147 expression levels than did their non-invasive counterparts. The shedding of GFP-tagged CD147 into isolated vesicles demonstrated that the vesicles originated from plasma cell membranes. EVs originating from invasive cancer cells were found to trigger migration, secretion of matrix metalloproteinases (MMPs), and invasion. The same induction of MMP activity was replicated using EVs obtained from urine samples of patients with invasive BLCA. EVs derived from cancer cell clones overexpressing TF and CD147 were produced in higher quantities and exhibited a higher invasive potential than those from control cancer cells. TFPI interfered with the effect when used in conjunction with the CD147 inhibitor, further suppressing homotypic EV-induced migration, MMP production, and invasion. CONCLUSIONS: Our findings suggest that combining a CD147 inhibitor with low molecular weight heparins to induce TFPI release may be a promising therapeutic approach for urothelial cancer management. This combination can potentially suppress the tumor-promoting actions of cancer-derived microvesicle-like EVs, including collective matrix invasion.

Small particles or vesicles released by cancer cells into their surroundings have the potential to stimulate the spread and growth of cancer cells. In this study, we focused on two specific molecules presented by these cancer cell-derived vesicles that could play a role in promoting the dissemination of cancer cells: a protein related to blood clotting and a protein on the cell surface.We found that large vesicles from bladder cancer cells that have the ability to spread had higher levels of these proteins than vesicles from nonspreading cancer cells. We also found that the former could make cancer cells move about more, produce more of a substance that helps cancer cells spread, and invade other tissues.To counteract the cancer-promoting actions of these vesicles, we examined the impact of combining a naturally occurring anticlotting protein that can be released by medications derived from heparin with an inhibitor targeting the cancer cell surface protein. We found that this combination stopped the vesicles from helping cancer cells move about more, produce more of the spreading substance, and invade other tissues.This approach of simultaneously targeting the two protein molecules present on cancer cell-derived vesicles might be a new way to treat bladder cancer.

The landscape of penile cancer research in Germany and Austria: a survey among professors in academic centers holding chair positions and results of a literature search.

BACKGROUND: Research on penile cancer (PeCa) is predominantly conducted in countries with centralized treatment of PeCa-patients. In Germany and Austria (G + A), no state-regulated centralization is established, and no information is available on how PeCa-research is organized. METHODS: Current research competence in PeCa was assessed by a 36-item questionnaire sent to all chairholders of urological academic centers in G + A. Based on PubMed records, all scientific PeCa-articles of 2012-2022 from G + A were identified. Current research trends were assessed by dividing the literature search into two periods (P1: 2012-2017, P2: 2018-2022). A bibliometric analysis was supplemented. RESULTS: Response rate of the questionnaire was 75%, a median of 13 (IQR: 9-26) PeCa-patients/center was observed in 2021. Retrospective case series were conducted by 38.9% of participating clinics, while involvement in randomized-controlled trials was stated in 8.3% and in basic/fundamental research in 19.4%. 77.8% declared an interest in future multicenter projects. 205 PeCa-articles were identified [median impact factor: 2.77 (IQR: 0.90-4.37)]. Compared to P1, P2 showed a significant increase in the median annual publication count (29 (IQR: 13-17) vs. 15 (IQR: 19-29), p < 0.001), in multicenter studies (79.1% vs. 63.6%, p = 0.018), and in multinational studies (53% vs. 28.9%, p < 0.001); the proportion of basic/fundamental research articles significantly declined (16.5% vs. 28.9%, p = 0.041). Four of the top-5 institutions publishing PeCa-articles are academic centers. Bibliometric analyses revealed author networks, primary research areas in PeCa, and dominant journals for publications. CONCLUSIONS: Given the lack of centralization in G + A, this analysis highlights the need for research coordination within multicenter PeCa-projects. The decline in basic/fundamental research should be effectively addressed by the allocation of funded research projects.

Impact of Peritoneal Interposition Flap on Patients Undergoing Robot-assisted Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

CONTEXT: Symptomatic lymphocele (sLC) occurs at a frequency of 2-10% after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). Construction of bilateral peritoneal interposition flaps (PIFs) subsequent to completion of RARP + PLND has been introduced to reduce the risk of lymphocele, and was initially evaluated on the basis of retrospective studies. OBJECTIVE: To conduct a systematic review and meta-analysis of only randomized controlled trials (RCTs) evaluating the impact of PIF on the rate of sLC (primary endpoint) and of overall lymphocele (oLC) and Clavien-Dindo grade ≥3 complications (secondary endpoints) to provide the best available evidence. EVIDENCE ACQUISITION: In accordance with the Preferred Reporting Items for Meta-Analyses statement for observational studies in epidemiology, a systematic literature search using the MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE databases up to February 3, 2023 was performed to identify RCTs. The risk of bias (RoB) was assessed using the revised Cochrane RoB tool for randomized trials. Meta-analysis used random-effect models to examine the impact of PIF on the primary and secondary endpoints. EVIDENCE SYNTHESIS: Four RCTs comparing outcomes for patients undergoing RARP + PLND with or without PIF were identified: PIANOFORTE, PerFix, ProLy, and PLUS. PIF was associated with odds ratios of 0.46 (95% confidence interval [CI] 0.23-0.93) for sLC, 0.51 (95% CI 0.38-0.68) for oLC, and 0.41 (95% CI 0.21-0.83) for Clavien-Dindo grade ≥3 complications. Functional impairment resulting from PIF construction was not observed. Heterogeneity was low to moderate, and RoB was low. CONCLUSIONS: PIF should be performed in patients undergoing RARP and simultaneous PLND to prevent or reduce postoperative sLC. PATIENT SUMMARY: A significant proportion of patients undergoing prostate cancer surgery have regional lymph nodes removed. This part of the surgery is associated with a risk of postoperative lymph collections (lymphocele). The risk of lymphocele can be halved via a complication-free surgical modification called a peritoneal interposition flap.

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Research protocol to identify progression and death amongst patients with metastatic hormone-sensitive prostate cancer treated with available treatments: PIONEER IMI's "big data for better outcomes" program.

Androgen deprivation therapy-based with or without first-generation anti-androgens, was the standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) for decades. However, the development of docetaxel chemotherapy and new androgen receptor-targeted agents, abiraterone acetate and prednisolone, apalutamide , enzalutamide and darolutamide (in combination with docetaxel chemotherapy) has proven that combination of treatments is more effective. Recently, intensification therapy, so-called "triplets", have emerged in the armamentarium of mHSPC treatment. Metastatic disease is a clinical state that remains poorly understood. The optimal diagnostic and management of patients with mHSPC are changing thanks to the development of new imaging techniques and therapies. The primary objective of this study is to develop and validate a predictive model for the occurrence of symptomatic progression, initiation of new treatments and death amongst patients with mHSPC treated with one of the approved treatment plans, on characteristics present at admission.

Enfortumab vedotin as a salvage option as 5th line therapy for metastatic urothelial bladder cancer.

A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion. After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab. Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control. The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).

Centralizing Penile Cancer Care in Germany and Austria: Just a Dream or a Fast-Approaching Reality? Results of a Survey Study among Urological Department Chairs and Modeling of Real Treatment Numbers of Penile Cancer Patients.

INTRODUCTION: In countries characterized by a centralization of therapy management, patients with penile cancer (PeCa) have shown improvements in guideline adherence and ultimately, improved carcinoma-specific survival. Germany and Austria (G + A) have no state-regulated centralization of PeCa management, and the perspectives of urological university department chairs (UUDCs) in these countries, who act as drivers of professional and political developments, on this topic are currently unknown. METHODS: Surveys containing 36 response options, including specific questions regarding perspectives on PeCa centralization, were sent to the 48 UUDC in G + A in January 2023. In addition to analyzing the responses, closely following the CROSS checklist, a modeling of the real healthcare situation of in-house PeCa patients in G + A was conducted. RESULTS: The response rate was 75% (36/48). 94% and 89% of the UUDCs considered PeCa centralization meaningful and feasible in the medium term, respectively. Among the UUDCs, 72% estimated centralization within university hospitals as appropriate, while 28% favored a geographically oriented approach. Additionally, 97% of the UUDCs emphasized the importance of bridging the gap until implementation of centralization by establishing PeCa second-opinion portals. No country-specific differences were observed. The median number of in-house PeCa cases at the university hospitals in G + A was 13 (interquartile range: 9-26). A significant positive correlation was observed between the annual number of in-house PeCa cases at a given university hospital and the perspective of the UUDCs that centralization as meaningful by its UUDC (0.024). Under assumptions permissible for modeling, the average number of in-house PeCa cases in academic hospitals in G + A was approximately 30 times higher than in nonacademic hospitals. CONCLUSION: This study provides the first data on the perspectives of UUDCs in G + A concerning centralization of PeCa therapy management. Even without state-regulated centralization in G + A, there is currently a clear focusing of PeCa treatments in university hospitals. Further necessary steps toward a structured PeCa centralization are discussed in this manuscript.

Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study.

BACKGROUND: Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. METHODS: These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models. RESULTS: Of 1052 patients, 63%, 81%, 54%, 27%, 5.7%, and 8.0% had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio = 0.68 [95% confidence interval: 0.53-0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40-1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33-1.44]; p = 0.32) and metachronous/low-volume (0.22 [0.09-0.55]; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease. CONCLUSION: TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC. CLINICAL TRIAL REGISTRATION: NCT02489318.

Real-world Outcomes and Predictive Biomarkers for 177Lutetium Prostate-specific Membrane Antigen Ligand Treatment in Metastatic Castration-resistant Prostate Cancer: A European Association of Urology Young Academic Urologists Prostate Cancer Working Group Multi-institutional Observational Study.

BACKGROUND: The European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers. OBJECTIVE: To assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models. RESULTS AND LIMITATIONS: A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046). CONCLUSIONS: 177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice. PATIENT SUMMARY: 177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.

Salvage high-dose-rate interventional radiotherapy (brachytherapy) for locally relapsed prostate cancer after radical prostatectomy and subsequent external irradiation.

Purpose: To report the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for macroscopic histologically confirmed local relapse of prostatic cancer after prostatectomy and subsequent external irradiation. Material and methods: A retrospective study of patients with prostate adenocarcinoma, treated with HDR-IRT for an isolated local relapse after prostatectomy and external irradiation at our institution (2010-2020). Treatment results and treatment related-toxicity were recorded. Clinical outcomes were analyzed. Results: Ten patients were identified. The median age was 63 years (range, 59-74 years), and the median follow-up time was 34 months (range, 10-68 months). Four patients had a biochemical relapse, and the mean time to prostate specific antigen (PSA) increase was 13 months. One-year biochemical failure-free survival (bFFS), 3-year bFFS, and 4-year bFFS were 80%, 60%, and 60%, respectively. Most of the treatment-related toxicities were grade 1-2. Two patients experienced grade 3 late genitourinary toxicity. Conclusions: HDR-IRT seems to be an effective treatment option showing acceptable toxicity for prostate cancer patients with isolated macroscopic histologically confirmed local relapse after prostatectomy and subsequent external irradiation.

The Role of Urine and Washing Cytology in Primary Transurethral Resection of Bladder Tumours.

INTRODUCTION: Urine cytology (UC) is a recommended tool for the diagnosis of urothelial malignancies. Thus far, no specific recommendations regarding the role of washing cytology (WC) have been included in the guidelines. The goal of our study was to analyse the relationship between the histology of transurethrally (transurethral resection of the bladder [TURBT]) resected bladder tumours (BCa) and intraoperative UC or WC findings. MATERIALS AND METHODS: Five hundred consecutive primary TURBT cases conducted between November 2010 and 2015 at our department of the University Hospital Luebeck were retrospectively analysed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of UC and WC were evaluated to detect BCa. Multivariate logistic regression models were fit to further examine associations between patient- and tumour-related factors and a bladder UC or WC positive for BCa. RESULTS: UC was performed in 297 patients, WC in 294 patients, and both in 261 patients. Sensitivity was 50.7% in UC, 58.1% in WC, and 62.1% for both tests combined. Specificity was 97.8% for UC, 98.0% for WC, and 96.4% for the combined tests. PPV was 98.0% for UC, 98.1% for WC, and 97.2% for combined tests. NPV was 47.8% for UC, 54.5% for WC, and 55.9% for the combined tests. The multivariate analyses revealed no association between positive UC or WC results and subsequent radical cystectomy (UC OR 1.35, 95% CI: 0.3-5.7; WC OR 2.0, 95% CI: 0.4-11.4). Neither UC nor WC was significantly correlated with local recurrence. CONCLUSIONS: Cytologic testing is an important diagnostic tool in BCa detection, showing acceptable sensitivity of around 60% and excellent specificity of over 90%. UC and WC present similar sensitivity. Our results advocate, however, against cytologic testing during primary TURBT, especially with regard to the lack of value in assessing the risk of recurrence. The clinical benefit of taking both types of samples at once is minimal. Furthermore, intraoperative WC collection does not reliably predict subsequent cystectomies.

Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study.

BACKGROUND: Initial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration. OBJECTIVE: To present the final data from TRITON2. DESIGN, SETTING, AND PARTICIPANTS: TRITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR; as per the modified Response Evaluation Criteria in Solid Tumor Version 1.1/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease by independent radiology review [IRR]); prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) was a key secondary endpoint. RESULTS AND LIMITATIONS: As of July 27, 2021 (study closure), TRITON2 had enrolled 277 patients, grouped by mutated gene: BRCA (n = 172), ATM (n = 59), CDK12 (n = 15), CHEK2 (n = 7), PALB2 (n = 11), or other DDR gene (Other; n = 13). ORR by IRR was 46% (37/81) in the BRCA subgroup (95% confidence interval [CI], 35-57%), 100% (4/4) in the PALB2 subgroup (95% CI, 40-100%), and 25% (3/12) in the Other subgroup (95% CI, 5.5-57%). No patients within the ATM, CDK12, or CHEK2 subgroups had an objective response by IRR. PSA50 response rates (95% CI) in the BRCA, PALB2, ATM, CDK12, CHEK2, and Other subgroups were 53% (46-61%), 55% (23-83%), 3.4% (0.4-12), 6.7% (0.2-32%), 14% (0.4-58%), and 23% (5.0-54%), respectively. CONCLUSIONS: The final TRITON2 results confirm the clinical benefit and manageable safety profile of rucaparib in patients with mCRPC, including those with an alteration in BRCA or select non-BRCA DDR gene. PATIENT SUMMARY: Almost half of TRITON2 patients with BRCA-mutated metastatic castration-resistant prostate cancer had a complete or partial tumor size reduction with rucaparib; clinical benefits were also observed with other DNA damage repair gene alterations.

[Are there any volume-related effects on treatment options for patients with penile cancer? Results of a survey among university hospitals in Germany and Austria]. / Gibt es fallzahlabhängige Effekte auf Behandlungsangebote für Patienten mit einem Peniskarzinom? Ergebnisse einer Umfrage an Universitätsklinika in Deutschland und Österreich.

BACKGROUND: Currently, 959 men in Germany and 67 in Austria are diagnosed with penile cancer each year, with an increase of approximately 20% in the last decade [RKI 2021, Statcube.at 2023]. Despite the rising incidence, the number of cases per hospital remains low. The median annual number of penile cancer cases at university hospitals in the DACH region was 7 patients (IQR 5-10) in 2017 [E-PROPS group 2021]. The compromised institutional expertise due to low case numbers is compounded with inadequate adherence to penile cancer guidelines, as shown in several studies. The centralization, which is rigorously implemented in countries such as the UK, enabled a significant increase in organ-preserving primary tumor surgery and stage-adapted lymphadenectomies, as well as improved patient survival in cases of penile cancer, resulting in a claim for a similar centralization in Germany and Austria. The aim of this study was to determine the current effects of case volume on penile cancer related treatment options at university hospitals in Germany and Austria. MATERIALS AND METHODS: In January 2023, a survey was sent to the heads of 48 urological university hospitals in Germany and Austria, including questions regarding case volume in 2021 (total number of inpatient and penile cancer cases), treatment options for primary tumors and inguinal lymphadenectomy (ILAE), the availability of a designated penile cancer surgeon, and the professional responsibility for systemic therapies in penile cancer. Correlations and differences related to case volume were statistically analyzed without adjustments. RESULTS: The response rate was 75% (n=36/48). In total, 626 penile cancer patients were treated at the 36 responding university hospitals in 2021, representing approximately 60% of the expected incidence in Germany and Austria. The annual median total number of cases was 2807 (IQR 1937-3653), and for penile cancer, it was 13 (IQR 9-26). There was no significant correlation between the total inpatient and penile cancer caseloads (p=0.34). The number of organ-preserving therapy procedures for the primary tumor, the availability of modern ILAE procedures, the presence of a designated penile cancer surgeon, and the responsibility for systemic therapies were not significantly influenced by the total inpatient or penile cancer case volume of the treating hospitals, regardless of whether the case volumes were dichotomized at the median or upper quartile. No significant differences between Germany and Austria were observed. CONCLUSION: Despite a significant increase in the annual number of penile cancer cases at university hospitals in Germany and Austria compared to 2017, we found no case volume-related effects on structural quality with respect to penile cancer therapy. In the light of the proven benefits of centralization, we interpret this result as an argument for the necessity of establishing nationally organized penile cancer centers with even higher case volumes compared to the status quo, in light of the proven benefits of centralization.

Definition and Diagnosis of Oligometastatic Bladder Cancer: A Delphi Consensus Study Endorsed by the European Association of Urology, European Society for Radiotherapy and Oncology, and European Society of Medical Oncology Genitourinary Faculty.

BACKGROUND: In contrast to other cancers, the concept of oligometastatic disease (OMD) has not been investigated in bladder cancer (BC). OBJECTIVE: To develop an acceptable definition, classification, and staging recommendations for oligometastatic BC (OMBC) spanning the issues of patient selection and the roles of systemic therapy and ablative local therapy. DESIGN, SETTING, AND PARTICIPANTS: A European consensus group of 29 experts, led by the European Association of Urology (EAU), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Medical Oncology (ESMO), and including members from all other relevant European societies, was established. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A modified Delphi method was used. A systematic review was used to build consensus questions. Consensus statements were extracted from two consecutive surveys. The statements were formulated during two consensus meetings. Agreement levels were measured to determine if consensus was achieved (≥75% agreement). RESULTS AND LIMITATIONS: The first survey included 14 questions and the second survey had 12. Owing to a considerable lack of evidence, which was the major limitation, definition was limited in the context of de novo OMBC, which was further classified as synchronous OMD, oligorecurrence, and oligoprogression. A maximum of three metastatic sites, all resectable or amenable to stereotactic therapy, was proposed as the definition of OMBC. Pelvic lymph nodes represented the only "organ" not included in the definition of OMBC. For staging, no consensus on the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography was reached. A favourable response to systemic treatment was proposed as the criterion for selection of patients for metastasis-directed therapy. CONCLUSIONS: A consensus statement on the definition and staging of OMBC has been formulated. This statement will help to standardise inclusion criteria in future trials, potentiate research on aspects of OMBC for which consensus was not achieved, and hopefully will lead to the development of guidelines on optimal management of OMBC. PATIENT SUMMARY: As an intermediate state between localised cancer and disease with extensive metastasis, oligometastatic bladder cancer (OMBC) might benefit from a combination of systemic treatment and local therapy. We report the first consensus statements on OMBC drawn up by an international expert group. These statements can provide a basis for standardisation of future research, which will lead to high-quality evidence in the field.

Radiomics vs radiologist in prostate cancer. Results from a systematic review.

PURPOSE: Radiomics in uro-oncology is a rapidly evolving science proving to be a novel approach for optimizing the analysis of massive data from medical images to provide auxiliary guidance in clinical issues. This scoping review aimed to identify key aspects wherein radiomics can potentially improve the accuracy of diagnosis, staging, and extraprostatic extension in prostate cancer (PCa). METHODS: The literature search was performed on June 2022 using PubMed, Embase, and Cochrane Central Controlled Register of Trials. Studies were included if radiomics were compared with radiological reports only. RESULTS: Seventeen papers were included. The combination of PIRADS and radiomics score models improves the PIRADS score reporting of 2 and 3 lesions even in the peripheral zone. Multiparametric MRI-based radiomics models suggest that by simply omitting diffusion contrast enhancement imaging in radiomics models can simplify the process of analysis of clinically significant PCa by PIRADS. Radiomics features correlated with the Gleason grade with excellent discriminative ability. Radiomics has higher accuracy in predicting not only the presence but also the side of extraprostatic extension. CONCLUSIONS: Radiomics research on PCa mainly uses MRI as an imaging modality and is focused on diagnosis and risk stratification and has the best future possibility of improving PIRADS reporting. Radiomics has established its superiority over radiologist-reported outcomes but the variability has to be taken into consideration before translating it to clinical practice.

[Prostate Cancer: Side-Effect Management for Androgen Deprivation Therapy]. / Prostatakarzinom: Nebenwirkungsmanagement unter Androgendeprivationstherapie.

Drug-based hormonal ablation is an essential component of therapy in hormone-sensitive advanced prostate cancer and as a backbone in castration resistance. LHRH agonists are among the most widely used medicinal products. Since these are usually given for life, therapy management is very important. Common side-effects typical of the substance class, such as weight gain, cardiovascular problems, hot flushes, erectile dysfunction or osteoporosis, can significantly reduce patients' quality of life and increase morbidity and mortality. This endangers adherence and, hence, treatment success. This paper provides an overview of how to deal with side-effects during LHRH therapy based on current data and practical experience.