Global burden, risk factors, and temporal trends of ureteral cancer: a comprehensive analysis of cancer registries.

BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

Learning curve for fusion magnetic resonance imaging targeted prostate biopsy and three-dimensional transrectal ultrasonography segmentation.

OBJECTIVE: To report the learning curve of multiple operators for fusion magnetic resonance imaging (MRI) targeted biopsy and to determine the number of cases needed to achieve proficiency. MATERIALS AND METHODS: All adult males who underwent fusion MRI targeted biopsy between February 2012 and July 2021 for clinically suspected prostate cancer (PCa) in a single centre were included. Fusion transrectal MRI targeted biopsy was performed under local anaesthesia using the Koelis platform. Learning curves for segmentation of transrectal ultrasonography (TRUS) images and the overall MRI targeted biopsy procedure were estimated with locally weighted scatterplot smoothing by computing each operator's timestamps for consecutive procedures. Non-risk-adjusted cumulative sum (CUSUM) methods were used to create learning curves for clinically significant (i.e., International Society of Urological Pathology grade ≥ 2) PCa detection. RESULTS: Overall, 1721 patients underwent MRI targeted biopsy in our centre during the study period. The median (interquartile range) times for TRUS segmentation and for the MRI targeted biopsy procedure were 4.5 (3.5, 6.0) min and 13.2 (10.6, 16.9) min, respectively. Among the 14 operators with experience of more than 50 cases, a plateau was reached after 40 cases for TRUS segmentation time and 50 cases for overall MRI targeted biopsy procedure time. CUSUM analysis showed that the learning curve for clinically significant PCa detection required 25 to 45 procedures to achieve clinical proficiency. Pain scores ranged between 0 and 1 for 84% of patients, and a plateau phase was reached after 20 to 100 cases. CONCLUSIONS: A minimum of 50 cases of MRI targeted biopsy are necessary to achieve clinical and technical proficiency and to reach reproducibility in terms of timing, clinically significant PCa detection, and pain.

Adjuvant intravesical therapy in intermediate-risk non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

A collaborative review of the microsatellite instability/deficient mismatch repair phenotype in patients with upper tract urothelial carcinoma.

OBJECTIVE: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC). METHOD: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients. RESULTS: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy. CONCLUSION: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence.

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Patients and general practitioner knowledge and perception of testicular self-examination for cancer.

PURPOSE: Testicular cancer (TC) predominantly affects young men and early detection enhances survival. However, uncertainty surrounds the impact of population-wide screening. Testicular self-examination (TSE) is a simple detection method but there is a gap in current practices that needs to be assessed. Our goal was to assess the perceptions and knowledge of male subjects in the general population (MP) and general practitioners (GPs) regarding TSE for TC. METHODS: Two distinct surveys evaluating knowledge and perceptions of TSE for TC were administered to GPs and MP, aged 15‒45-years. Factors that could favour the realisation of TSE or improve the knowledge of TC were evaluated by multivariable logistic regression. RESULTS: Overall, 1048 GPs (mean (SD) age: 35.1 ± 10.3 years) and 1032 MP (mean (SD) age: 27 ± 8.2 years) answered the survey. Among the GPs, only 93 (8.9%) performed scrotal examination for TC screening. Although the majority (n = 993, 94.8%) were aware of the age of onset of TC, most (n = 768, 73.3%) did not know the overall survival rate from TC. GPs familiar with the guidelines were more likely to explain TSE to their patients (OR = 2.5 [95% CI 1.5‒4.1]; p < 0.01). Among the MP, 800 (77.5%) admitted that they did not know how to perform TSE and 486 (47.1%) did not know the main symptoms associated with TC. MP who had already undergone TC screening were more likely to be familiar with the main symptoms (OR = 2.1 [95% CI 1.6‒2.7]; p < 0.001) and MP who knew someone with TC or who had already undergone TC screening were more likely to be aware of the correct prevalence of TC (OR = 1.9 [95% CI 1.3‒2.7], p < 0.01; and OR = 1.6 [95% CI 1.2‒2.1], p < 0.01; respectively). CONCLUSION: The knowledge of both GPs and MP regarding TC could be improved. TSE screening and knowing someone close with TC improved the awareness of our subjects.

Open versus robotic partial nephrectomy in obese patients: a multi-institutional propensity score-matched analysis (UroCCR 43-Robese study).

INTRODUCTION: There is limited evidence on the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN) in obese patients (BMI ≥ 30 kg/m2). In this study, we aimed to compare perioperative and oncological outcomes of RPN and OPN. METHODS: We relied on data from patients who underwent PN from 2009 to 2017 at 16 departments of urology participating in the UroCCR network, which were collected prospectively. In an effort to adjust for potential confounders, a propensity-score matching was performed. Perioperative outcomes were compared between OPN and RPN patients. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Overall, 1277 obese patients (932 robotic and 345 open were included. After propensity score matching, 166 OPN and 166 RPN individuals were considered for the study purposes; no statistically significant difference among baseline demographic or tumor-specific characteristics was present. A higher overall complication rate and major complications rate were recorded in the OPN group (37 vs. 25%, p = 0.01 and 21 vs. 10%, p = 0.007; respectively). The length of stay was also significantly longer in the OPN group, before and after propensity-score matching (p < 0.001). There were no significant differences in Warm ischemia time (p = 0.66), absolute change in eGFR (p = 0.45) and positive surgical margins (p = 0.12). At a median postoperative follow-up period of 24 (8-40) months, DFS and OS were similar in the two groups (all p > 0.05). CONCLUSIONS: In this study, RPN was associated with better perioperative outcomes (improvement of major complications rate and LOS) than OPN. The oncological outcomes were found to be similar between the two approaches.

Differential effect of surgical technique on intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial cancer: a systematic review and Meta-analysis.

CONTEXT: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. OBJECTIVE: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. EVIDENCE ACQUISITION: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. EVIDENCE SYNTHESIS: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively). CONCLUSIONS: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

Salvage procedures for infected penile implants: A comprehensive review and analysis of functional outcomes.

BACKGROUND: The salvage procedure for infected penile implants (IPs) has been a subject of interest since its inception in the late 1980s, yet its widespread adoption remains limited. The aim of this study was to realize a systematic literature review to provide a comprehensive analysis of salvage techniques for IPs and assess their efficacy, specifically focusing on functional success. METHODS: A systematic literature review was conducted using PubMed, employing Mesh terms related to penile prosthesis, penile implant, infection, and salvage procedures. Articles in French or English were considered for the final analysis, with exclusion of literature reviews. RESULTS: Fifteen articles detailing various salvage techniques for IPs were identified. Mulcahy's initial technique was described in 1996, and consisted of complete removal of infected components, extensive lavage, and subsequent replacement with a similar implant. Success rates ranged from 80% to 100%, with emerging trends favoring the use of malleable implants during salvage. Unfortunately, functional data remained limited. When salvage penile prosthesis placement involved a malleable prosthesis, between 20% and 33% of patients underwent conversion to hydraulic prosthesis. CONCLUSION: The salvage procedure for infected penile implants is a reliable method, with success rates surpassing 80%. The need for comparative studies assessing the type of implant used during salvage is required to tailor conservative management strategies for optimal patient outcomes. Finally, few data have been published regarding subsequent conversions from malleable penile implants to hydraulic penile implants after salvage.

Radiotherapy Combined with a Radiosensitizer for Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Carcinoma In Situ Bladder Cancer: An Open-label, Single-arm, Multicenter, Phase 2 European Organisation for Research and Treatment of Cancer Trial.

Radical cystectomy with pelvic lymph node dissection and urinary diversion is the standard of care for patients with bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). However, many patients are unwilling or unable to undergo such major surgery associated with high morbidity and a negative impact on quality of life. Chemoradiotherapy is an established treatment option for muscle-invasive bladder cancer. However, it has not been investigated adequately in NMIBC until now. The European Organisation for Research and Treatment of Cancer (EORTC) 2235 study (NCT06310369) is designed as a multicenter, prospective, international, phase 2 trial of moderate hypofractionated radiotherapy combined with a radiosensitizer in BCG-unresponsive NMIBC patients with carcinoma in situ (CIS) who are not eligible for or declined to undergo radical cystectomy. Patients who have received nadofaragene firadenovec or TAR-200 are eligible. The primary endpoint is the 6-mo complete response (CR) rate defined by the absence of CIS proven by a control biopsy of the bladder. The secondary endpoints include overall survival, progression-free survival, durability of CR, grade 3-4 adverse events rate, patients' quality of life, and organ preservation rate. PATIENT SUMMARY: Intravesical instillation of bacillus Calmette-Guérin is the standard treatment of non-muscle-invasive, also coined as superficial, bladder cancer. In case the cancer recurs, even superficially, there is no other proven treatment than a radical cystectomy-the surgical removal of the bladder. Although the surgical technique has improved dramatically over the past few years, it remains contraindicated in patients with severe comorbidities. In addition, because it affects the quality of life, patients may reject this option. This study will assess the efficacy of external beam radiotherapy, a robust alternative to surgery in muscle-invasive bladder cancer. Radiotherapy will be administered 5 d a week for 4 wk. It will be associated with a "radiosensitizer," an intravenous or oral drug, during the radiotherapy treatment. The study will measure the proportion of patients remaining recurrence free at 6 mo and thereafter. It will also evaluate the safety of the treatment and its impact on quality of life.

The State of Intermediate Clinical Endpoints as Surrogates for Overall Survival in Prostate Cancer in 2024.

In the past, selection of intermediate clinical endpoints (ICEs) in prostate cancer (PCa) trials largely depended on qualitative assessments; however, the advancing quality of research necessitates a robust correlation with overall survival (OS). This review summarises the results from several high-quality meta-analyses that explored the validity of ICEs as surrogates for OS. We found strong evidence that metastasis-free survival can serve as an ICE in localized PCa. In advanced disease, valid ICEs were identified only within the context of metastatic hormone-sensitive PCa, including radiological and clinical progression-free survival; however, concerns remain regarding their use owing to the limited generalisability of the data used to validate their surrogacy. PATIENT SUMMARY: Intermediate clinical endpoints can reduce the costs of trials and allow earlier introduction of new treatment methods. This article summarises results from studies verifying the validity of these endpoints as surrogates for overall survival.

A Comprehensive National Survey of Prostate-specific Antigen Testing and Prostate Cancer Management in France: Uncovering Regional and Temporal Disparities.

We report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men. All prostate-specific antigen (PSA) blood tests performed between 2006 and 2018 were recorded in a National Health registry, which allowed to identify 692516 men diagnosed with PC and a control population consisting of 3899509 men without PC. PSA tests, age at diagnosis, treatments, and survival were analysed. Their management was analysed by age range and compared in the different French regions. Disparities were found in age at PSA testing and management approaches (surveillance, and local and systemic therapies). We found that 50% of men had received five PSA blood tests, but the first PSA test was taken late in life, with a peak in the decade between 65 and 75 yr of age. Adoption of monitoring was low (12%). Older men appeared to receive a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality, but cautious interpretation of our data is warranted in view of competing morbidities and other causes of death. The incidence of metastases at diagnosis, indicated by the use of systemic therapies, increased progressively from 2011 onwards. PATIENT SUMMARY: In this study, we report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men, including 692516 patients with PC. We found that the first prostate-specific antigen test is taken too late in life, leading to a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality.

Novel Delivery Systems and Pharmacotherapeutic Approaches for the Treatment of Non-muscle-invasive Bladder Cancer.

BACKGROUND AND OBJECTIVE: Therapeutic options for patients with non-muscle-invasive bladder cancer (NMIBC) have traditionally been limited to intravesical immunotherapy or chemotherapy. A considerable number of new options have been investigated in recent years. Our aim was to review the efficacy and toxicity of novel therapeutic options (results already reported or currently under investigation) for patients with NMIBC. METHODS: We assessed the efficacy of various novel therapeutic options by examining key endpoints in diverse settings, including recurrence, progression, overall survival, disease-specific survival, and complete response. We identified the principal advantages and limitations for each option. Safety was predominantly evaluated as the incidence of grade ≥3 adverse events. Our investigation focused on evidence from scientific articles and congress abstracts published in English within the past 5 yr. KEY FINDINGS AND LIMITATIONS: To date, pembrolizumab, nadofaragene firadenovec, and the combination of BCG with N-803 have received US Food and Drug administration approval for the treatment of BCG-unresponsive carcinoma in situ of the bladder (with or without papillary tumours). Five phase 3 trials are recruiting BCG-naïve patients with high-risk NMIBC. There is increasing interest in an ablative rather than an adjuvant approach for patients with intermediate-risk NMIBC. CONCLUSIONS AND CLINICAL IMPLICATIONS: Novel drugs and device-assisted drug delivery systems are on the verge of changing the treatment of NMIBC. Novel intravesical options seem to have the same efficacy with fewer adverse events in comparison to systemic therapies. PATIENT SUMMARY: We reviewed new therapy options for non-muscle-invasive bladder cancer. Two agents (pembrolizumab and nadofaragene firadenovec) have been approved to date. Ongoing trials are assessing direct delivery of drugs in solution into the bladder. This route seems to have similar efficacy and fewer side effects than intravenous immunotherapy.

Management of patients with muscle-invasive bladder cancer with clinical evidence of pelvic lymph node metastases.

Identification of clinically positive pelvic lymph node metastases (cN+) in patients with muscle-invasive bladder cancer is currently challenging, as the diagnostic accuracy of available imaging modalities is limited. Conventional CT is still considered the gold-standard approach to diagnose lymph node metastases in these patients. The development of innovative diagnostic methods including radiomics, artificial intelligence-based models and molecular biomarkers might offer new perspectives for the diagnosis of cN+ disease. With regard to the treatment of these patients, multimodal strategies are likely to provide the best oncological outcomes, especially using induction chemotherapy followed by radical cystectomy and pelvic lymph node dissection in responders to chemotherapy. Additionally, the use of adjuvant nivolumab has been shown to decrease the risk of recurrence in patients who still harbour ypT2-T4a and/or ypN+ disease after surgery. Alternatively, the use of avelumab maintenance therapy can be offered to patients with unresectable cN+ tumours who have at least stable disease after induction chemotherapy alone. Lastly, patients with cN+ tumours who are not responding to induction chemotherapy are potential candidates for receiving second-line treatment with pembrolizumab.

Short-term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients with Unfavorable Intermediate-risk Prostate Cancer: The Darius (AFU-GETUG P15) Phase 2 Trial Protocol.

BACKGROUND: Combination of androgen deprivation therapy (ADT) with external beam radiation therapy (EBRT) is a standard of care for patients with intermediate-risk prostate cancer (PCa). However, 6 months of ADT generates multiple side effects impacting quality of life (QoL). Darolutamide (an androgen receptor targeting agent [ARTA]) is associated with low blood-brain barrier penetrance and less drug-drug interaction. OBJECTIVE: To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa. DESIGN, SETTING, AND PARTICIPANTS: The DARIUS trial is a multicenter randomized non comparative phase 2 trial, randomizing the 6-months darolutamide + EBRT arm versus 6-months ADT + EBRT in patients with unfavorable intermediate-risk PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint is a biological response defined as prostate-specific antigen ≤0.1 ng/ml at month six of darolutamide or ADT. The key secondary endpoints are biochemical recurrence-free survival, disease-free survival, safety, and QoL. Ancillary studies using radiomics and genomic classifier are planned. Sixty-two patients will be included. RESULTS AND LIMITATIONS: In this population of patients requiring ADT combined with EBRT, the use of an ARTA alone, such as darolutamide, may demonstrate antitumoral efficacy while minimizing toxicity and maintaining QoL. Limitations are mainly inherent to the open-label design of this study. CONCLUSIONS: Six months of darolutamide + EBRT compared with 6 months of ADT + EBRT may be efficient in terms of a biological response, avoiding toxicity and altered QoL attributable to ADT in patients with unfavorable intermediate-risk PCa. PATIENT SUMMARY: The ongoing DARIUS clinical trial assesses short-term (6 months) darolutamide treatment in association with external beam radiation therapy in men with localized prostate cancer. The trial investigates whether single-agent darolutamide can improve the biological response while maintaining a favorable tolerability profile.

Primary urethral carcinoma: Recommendations of the oncology committee of the French Urology Association.

Primary urethral carcinoma (PUC) is defined as a tumor process arising within the urethra, with no history of other urinary tract localization or synchronous tumor of the urinary tract. The most common histological types are urothelial carcinoma (UC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). In men, UC predominates, while AC is rare. In women, AC affects around one in two patients, while EC and UC are equally divided between the remaining cases. Diagnosis is often delayed, and requires endoscopic examination with biopsies. MRI is the gold standard for local staging. FDG-PET scan can help in cases of doubt about regional or distant extension. The prognosis remains unfavorable despite aggressive surgical treatment. Multimodal management combining surgery, radiotherapy and chemotherapy appears to improve prognosis in severe forms.

Continent cutaneous diversion: Unveiling the interplay of neuro-urology and oncological challenges.

OBJECTIVES: The objective of our study is to demonstrate the practical application of continent cutaneous urinary diversion (CCUD) in oncological patients, with a focus on various aspects of the procedure: surgical challenges, functional outcomes, and quality of life. MATERIALS AND METHODS: We studied the perioperative and follow-up data of patients who underwent cystectomy for cancer associated with CCUD (Mitrofanoff, Monti or Casale). We retrospectively analyzed complications within 30days and beyond 30days post-surgery. We evaluated oncological outcomes. Patients' quality of life was assessed using the Bladder Cancer Index (BCI) questionnaire. Results are given on an intention-to-treat basis. RESULTS: A total of 24 patients were included in the study (July 2001 and May 2022), with a median follow-up of 62.5months. We report three deaths due to neoplasic recurrence. Forty-six percent had an early postoperative complication, two of whom required revision surgery. Overall, the medium-term complication rate was 70% and the reoperation rate was 62%. There were 8 stomal cutaneous stenoses (33%) and 3 uretero-ileal stenoses (12.5%). Overall satisfaction was rated at 9.2/10 on average, and body image was unaltered or slightly altered in 62.5% of patients. Of the patients who responded to the BCI, 75% had complete continence. DISCUSSION: The experience gained with continent stomas in neuro-urology has allowed, in carefully selected cases, to offer patients an alternative that can improve their quality of life in a context already burdened by the shadow of cancer. CCUD can be proposed as an alternative to Bricker diversion in cases of urethral invasion or a high risk of neobladder incontinence, in selected patients.

UroPredict: Machine learning model on real-world data for prediction of kidney cancer recurrence (UroCCR-120).

Renal cell carcinoma (RCC) is most often diagnosed at a localized stage, where surgery is the standard of care. Existing prognostic scores provide moderate predictive performance, leading to challenges in establishing follow-up recommendations after surgery and in selecting patients who could benefit from adjuvant therapy. In this study, we developed a model for individual postoperative disease-free survival (DFS) prediction using machine learning (ML) on real-world prospective data. Using the French kidney cancer research network database, UroCCR, we analyzed a cohort of surgically treated RCC patients. Participating sites were randomly assigned to either the training or testing cohort, and several ML models were trained on the training dataset. The predictive performance of the best ML model was then evaluated on the test dataset and compared with the usual risk scores. In total, 3372 patients were included, with a median follow-up of 30 months. The best results in predicting DFS were achieved using Cox PH models that included 24 variables, resulting in an iAUC of 0.81 [IC95% 0.77-0.85]. The ML model surpassed the predictive performance of the most commonly used risk scores while handling incomplete data in predictors. Lastly, patients were stratified into four prognostic groups with good discrimination (iAUC = 0.79 [IC95% 0.74-0.83]). Our study suggests that applying ML to real-world prospective data from patients undergoing surgery for localized or locally advanced RCC can provide accurate individual DFS prediction, outperforming traditional prognostic scores.

A Systematic Review and Meta-analysis of the Impact of Local Therapies on Local Event Suppression in Metastatic Hormone-sensitive Prostate Cancer.

CONTEXT: It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression. OBJECTIVE: To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP). EVIDENCE ACQUISITION: Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT). EVIDENCE SYNTHESIS: Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract. CONCLUSIONS: In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting. PATIENT SUMMARY: Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.

PARP inhibitors in prostate cancers, is it time for combinations?

Despite several improvements in outcomes, metastatic prostate cancer remains deadly. Alterations in the homologous recombination repair (HRR) pathway are associated with more aggressive disease. Olaparib and rucaparib, two poly-ADP-ribose polymerase (PARP) inhibitors, have received approval from the authorities of several countries for their anti-tumoral effects in patients with metastatic castration-resistant prostate cancers harboring HRR gene alterations, in particular BRCA2. More recently, it has been hypothesized that new hormonal therapies (NHTs) and PARP inhibitors (PARPi) could have synergistic actions and act independently of HRR deficiency. This review proposes to discuss the advantages and disadvantages of PARPi used as monotherapy or in combination with NHTs and whether there is a need for molecular selection.