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BACKGROUND: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment. METHODS: Post-hoc analysis assessed patients receiving 240 mg/day apalutamide (525 TITAN and 806 SPARTAN) or placebo (527 TITAN and 401 SPARTAN) with ongoing ADT, stratified by age groups. Prostate-specific antigen declines, radiographic progression-free survival, metastasis-free survival, overall survival (OS), HRQoL and safety were assessed using descriptive statistics, Kaplan-Meier method, Cox proportional-hazards model and mixed-effects model for repeated measures. RESULTS: Hazard ratios (95% confidence intervals) generally favoured apalutamide plus ADT versus ADT alone across all endpoints regardless of age; e.g., OS values were 0.57 (0.40-0.80), 0.70 (0.54-0.91) and 0.74 (0.40-1.39) (TITAN) and 0.39 (0.19-0.78), 0.89 (0.69-1.16) and 0.81 (0.58-1.15) (SPARTAN) in patients aged

Simple Summary: Worldwide, prostate cancer is the second most common cancer affecting men. Both the disease and treatments like surgery, radiotherapy, or drug therapy can cause unpleasant side effects, such as fatigue, muscle loss, and reduced quality of life. Exercise, particularly strength training and aerobic workouts, has been suggested to help reduce these effects. This study reviewed findings from controlled trials to evaluate how strength training, aerobic exercise, or a combination of both, affected men receiving prostate cancer treatment. The results show that combining strength and aerobic exercise significantly improves quality of life, especially in general health, mental clarity, and sexual wellbeing. Strength training alone helped by increasing muscle mass and lowering body fat. Both types of exercise improved physical strength and fitness. However, the training had no impact on laboratory results like PSA or cholesterol levels. More research is needed on long-term effects, particularly of aerobic exercise alone. Background: Prostate cancer (PC) and its treatment are often associated with side effects such as fatigue, muscle loss, and diminished quality of life (QoL). Physical exercise, particularly resistance training (RT) and aerobic training (AT), has been suggested as a strategy to mitigate these effects. However, the comparative efficacy of RT, AT, and combined RT/AT on QoL, body composition, physical fitness, and laboratory markers in PC patients is still insufficiently understood. Methods: Randomized controlled trials (RCTs) investigating structured RT, AT, or combined RT/AT programs in PC patients undergoing various treatments were included. The primary outcome was QoL, assessed using EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Secondary outcomes included body composition, fitness, and laboratory parameters. The studies were sourced from PubMed, Embase, and CENTRAL through May 2024. The effect sizes were pooled using random-effects models, and the risk of bias was systematically assessed following the GRADE approach. Results: A total of 30 RCTs, encompassing 2216 PC patients, were analyzed. Combined RT/AT significantly improved QoL subdomains, including global health, and cognitive and sexual function, while reducing fatigue and urinary symptoms. RT alone improved body composition by increasing lean body mass and reducing body fat percentage. Both RT and combined RT/AT enhanced strength (chest and leg press) and VO2peak. No significant changes were observed in laboratory markers, such as PSA or lipid levels. The effects of isolated AT remain unclear due to limited data. Conclusions: RT and combined RT/AT significantly improve QoL, fitness, and body composition in PC patients, with no detectable effect on PSA or lipid levels. Further research is needed to elucidate the specific effects of AT and to investigate long-term outcomes. [ABSTRACT FROM AUTHOR]

What is this summary about? This is a summary of a paper that describes the results of the SPARTAN and TITAN studies, which looked at whether a treatment called apalutamide can help treat individuals with advanced prostate cancer. The SPARTAN study included 1207 participants with nonmetastatic castration-resistant prostate cancer (or nmCRPC). The TITAN study included 1052 participants with metastatic castration-sensitive prostate cancer (or mCSPC). Treatment with apalutamide was compared with treatment with placebo. In both studies, all participants were also given androgen deprivation therapy (or ADT), which has been used for many years for the treatment of prostate cancer. The results showed that treatment with apalutamide plus ADT increased participants' survival time while their health-related quality of life stayed the same, compared with placebo plus ADT. Also, apalutamide plus ADT increased the length of time that the cancer did not spread to other parts of the body (metastasize) or did not continue to grow. In both studies, treatment with apalutamide plus ADT was associated with a deep decline in blood prostate-specific antigen (or PSA) levels (called a deep PSA decline). This additional analysis of the SPARTAN and TITAN studies was performed to understand whether the deep PSA decline in participants who received apalutamide plus ADT was linked to their overall health-related quality of life. What were the results of the additional analysis? In participants who received apalutamide plus ADT, those who achieved a deep PSA decline after the start of treatment had a greater chance that their health-related quality of life would remain stable. When participants achieved a deep PSA decline at 3 months after the start of treatment, the benefit to their health-related quality of life, including physical wellbeing, was even greater. What do these results mean for individuals with advanced prostate cancer? For individuals with advanced prostate cancer, it is important to monitor both PSA decline and any impacts on health-related quality of life. These results will help doctors and other healthcare professionals have a better understanding of patients' cancer experience and the impact of their treatment. Clinical Trial Registration:NCT01946204 (SPARTAN) and, NCT02489318 (TITAN) (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Objectives: To compare Uromonitor® (U‐Monitor Lda, Porto, Portugal), a multitarget DNA assay that detects mutated proto‐oncogenes (telomerase reverse transcriptase [TERT], fibroblast growth factor receptor 3 [FGFR‐3], Kirsten rat sarcoma viral oncogene homologue [KRAS]), with urine cytology in the urine‐based diagnosis of urothelial carcinoma of the bladder (UCB) within a multicentre real‐world setting. Patients and Methods: This multicentre, prospective, double‐blind study was conducted across four German urological centres from 2019 to 2024. We evaluated the diagnostic performance of Uromonitor compared to urine cytology in a cohort of patients with UCB and in healthy controls within a real‐world setting. Sensitivity, specificity, positive‐predictive value (PPV), negative‐predictive value (NPV), and accuracy of the tests were measured, in addition to multivariate analyses to assess the ability of individual proto‐oncogene mutations in detecting UCB. The biometric sample size was designed to achieve a 10% difference in sensitivity. Results: Patients with UCB comprised 63.7% (339/532) of the study group. Uromonitor showed a sensitivity, specificity, PPV, NPV, accuracy, and an area‐under‐the‐curve of 49.3%, 93.3%, 92.8%, 51.1%, 65.2%, and 0.713%, respectively. These metrics did not demonstrate statistical superiority over urine cytology in terms of sensitivity (44.6%; P = 0.316). Moreover, the comparison of additional test parameters, as well as the comparison within various sensitivity analyses, yielded no significant disparity between the two urinary tests. Multivariate logistic regression underscored the significant predictive value of a positive Uromonitor for detecting UCB (odds ratio [OR] 9.03; P < 0.001). Furthermore, mutations in TERT and FGFR‐3 were independently associated with high odds of UCB detection (OR 13.30 and 7.04, respectively), while KRAS mutations did not exhibit predictive capability. Conclusion: Despite its innovative approach, Uromonitor fell short of confirming the superior results anticipated from previous studies in this real‐world setting. The search for an optimal urine‐based biomarker for detecting and monitoring UCB remains ongoing. Results from this study highlight the complexity of developing non‐invasive diagnostic tools and emphasise the importance of continued research efforts to refine these technologies. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between achievement of prostate‐specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti‐androgen' (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration‐sensitive prostate cancer (mCSPC). Patients and Methods: Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen‐deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2–>0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression‐free survival (rPFS), overall survival (OS), time to castration‐resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan–Meier methods were used. Results: By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide‐treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14–0.54), OS (HR 0.24, 95% CI 0.13–0.43), TTCRPC (HR 0.2, 95% CI 0.11–0.38), and TTPP (HR 0.11, 95% CI 0.04–0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06–0.22; P < 0.001) in apalutamide‐treated patients. Conclusions: In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy. Patient Summary: Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit. [ABSTRACT FROM AUTHOR]

The integration of artificial intelligence, particularly Large Language Models (LLMs), has the potential to significantly enhance therapeutic decision-making in clinical oncology. Initial studies across various disciplines have demonstrated that LLM-based treatment recommendations can rival those of multidisciplinary tumor boards (MTBs); however, such data are currently lacking for urological cancers. This preparatory study establishes a robust methodological foundation for the forthcoming CONCORDIA trial, including the validation of the System Causability Scale (SCS) and its modified version (mSCS), as well as the selection of LLMs for urological cancer treatment recommendations based on recommendations from ChatGPT-4 and an MTB for 40 urological cancer scenarios. Both scales demonstrated strong validity, reliability (all aggregated Cohen's K > 0.74), and internal consistency (all Cronbach's Alpha > 0.9), with the mSCS showing superior reliability, internal consistency, and clinical applicability (p < 0.01). Two Delphi processes were used to define the LLMs to be tested in the CONCORDIA study (ChatGPT-4 and Claude 3.5 Sonnet) and to establish the acceptable non-inferiority margin for LLM recommendations compared to MTB recommendations. The forthcoming ethics-approved and registered CONCORDIA non-inferiority trial will require 110 urological cancer scenarios, with an mSCS difference threshold of 0.15, a Bonferroni corrected alpha of 0.025, and a beta of 0.1. Blinded mSCS assessments of MTB recommendations will then be compared to those of the LLMs. In summary, this work establishes the necessary prerequisites prior to initiating the CONCORDIA study and validates a modified score with high applicability and reliability for this and future trials. [ABSTRACT FROM AUTHOR]

Defining meaningful endpoints for research of early-stage high-risk prostate cancer is challenging, with established measures such as overall survival and metastasis-free survival facing limitations related to feasibility and adequate reflection of patient relevance. Developing endpoints must cater to diverse perspectives across scientific, clinical, regulatory, and patient viewpoints. Endpoints such as pathological complete response, no evidence of disease, and prevention of prostate-specific antigen relapse may reflect patient benefit by accounting for diagnostic and treatment burdens. [ABSTRACT FROM AUTHOR]

Introduction: This study assessed the potential of large language models (LLMs) as educational tools by evaluating their accuracy in answering questions across urological subtopics. Methods: Three LLMs (ChatGPT-3.5, ChatGPT-4, and Bing AI) were examined in two testing rounds, separated by 48 h, using 100 Multiple-Choice Questions (MCQs) from the 2022 European Board of Urology (EBU) In-Service Assessment (ISA), covering five different subtopics. The correct answer was defined as "formal accuracy" (FA) representing the designated single best answer (SBA) among four options. Alternative answers selected from LLMs, which may not necessarily be the SBA but are still deemed correct, were labeled as "extended accuracy" (EA). Their capacity to enhance the overall accuracy rate when combined with FA was examined. Results: In two rounds of testing, the FA scores were achieved as follows: ChatGPT-3.5: 58% and 62%, ChatGPT-4: 63% and 77%, and BING AI: 81% and 73%. The incorporation of EA did not yield a significant enhancement in overall performance. The achieved gains for ChatGPT-3.5, ChatGPT-4, and BING AI were as a result 7% and 5%, 5% and 2%, and 3% and 1%, respectively (p > 0.3). Within urological subtopics, LLMs showcased best performance in Pediatrics/Congenital and comparatively less effectiveness in Functional/BPS/Incontinence. Conclusion: LLMs exhibit suboptimal urology knowledge and unsatisfactory proficiency for educational purposes. The overall accuracy did not significantly improve when combining EA to FA. The error rates remained high ranging from 16 to 35%. Proficiency levels vary substantially across subtopics. Further development of medicine-specific LLMs is required before integration into urological training programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Better tests are needed to detect serious bladder cancer (BC), additionally avoiding unnecessary follow-up tests. This study looked at Uromonitor®, a urine-based test, which checks for specific changes in DNA related to BC. Previous tests were good but not perfect, and more information is needed to use this new one in daily routine. We gathered and analyzed data from four studies using Uromonitor®, involving nearly 1200 urine tests. Results showed that Uromonitor® detects existing BC with an accuracy of over 90%. It rarely indicates BC in cases where BC is absent (reaching 97% accuracy). In comparison with urinary cytology, Uromonitor® spotted BC better. If applied in a group of 1000 people including around 15% with active BC, this test could prevent about 825 unnecessary cystoscopies while missing around 30 BC cases. However, more studies are needed to finally confirm the performance of Uromonitor®. Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately detecting high-grade bladder-cancer without false-negative results. Such UBDTs have not been comprehensively described upon a broad, validated dataset, resulting in cautious guideline recommendations. Uromonitor®, a urine-based DNA-assay detecting hotspot alterations in TERT, FGFR3, and KRAS, shows promising initial results. However, a systematic review merging all available data is lacking. Studies investigating the diagnostic performance of Uromonitor® in NMIBC until November 2023 were identified in PubMed, Embase, Web-of-Science, Cochrane, Scopus, and medRxiv databases. Within aggregated analyses, test performance and area under the curve/AUC were calculated. This project fully implemented the PRISMA statement. Four qualifying studies comprised a total of 1190 urinary tests (bladder-cancer prevalence: 14.9%). Based on comprehensive analyses, sensitivity, specificity, positive-predictive value/PPV, negative-predictive value/NPV, and test accuracy of Uromonitor® were 80.2%, 96.9%, 82.1%, 96.6%, and 94.5%, respectively, with an AUC of 0.886 (95%-CI: 0.851–0.921). In a meta-analysis of two studies comparing test performance with urinary cytology, Uromonitor® significantly outperformed urinary cytology in sensitivity, PPV, and test accuracy, while no significant differences were observed for specificity and NPV. This systematic review supports the use of Uromonitor® considering its favorable diagnostic performance. In a cohort of 1000 patients with a bladder-cancer prevalence of ~15%, this UBDT would avert 825 unnecessary cystoscopies (true-negatives) while missing 30 bladder-cancer cases (false-negatives). Due to currently limited aggregated data from only four studies with heterogeneous quality, confirmatory studies are needed. [ABSTRACT FROM AUTHOR]