Local salvage therapies in patients with radio-recurrent prostate cancer following external beam radiotherapy: a systematic review and meta-analysis.

INTRODUCTION: To date, radio-recurrent prostate cancer (PCa) ranks as the fourth most common urological malignancy when considering the number of men with localized PCa who undergo radiation treatment and subsequently experience a biochemical recurrence. This systematic review aimed to summarize available evidence about the outcomes of local salvage strategies in patients with local PCa recurrence following primary external-beam radiation therapy (EBRT). METHODS: We conducted a comprehensive bibliographic search on MEDLINE, Scopus, and Web of Science Core Collection databases in October 2023 to identify studies published in the last 20 years evaluating outcomes of local salvage procedures in patients with locally radio-recurrent PCa following EBRT. The meta-analysis was performed using ProMeta 3 software when two or more studies reported the same outcome. The effect size (ES) was estimated using rates reported with its 95% confidence interval (CI). RESULTS: Overall, 28 studies (6 prospective and 22 retrospective) including 1544 patients were included in the review. Two-year recurrence-free survival (RFS) was 84.0% (95% CI: 67.0-93.0%), 69.0% (95% CI: 42.0-87.0%), 58.0% (95% CI: 43.0-71.0%), and 45% (95% CI: 38.0-52.0%), for patients undergoing brachytherapy (BT), EBRT, Cryotherapy and High-Intensity Focused Ultrasound (HIFU), respectively. After salvage prostatectomy, RFS ranged from 75% to 78.5% at a median follow-up ranging from 18 to 35 months. Estimates for severe gastrointestinal toxicity were 2%, 3%, 3%, 4%, and 11% following cryotherapy, BT, HIFU, EBRT, and salvage radical prostatectomy, respectively. CONCLUSIONS: In patients who underwent EBRT as primary treatment, prostate salvage re-irradiation through BT or EBRT represents the modality providing the best balance between efficacy and safety. Unfortunately, due to the low level of evidence, strong recommendations regarding the choice of any of these techniques cannot be made.

Bladder sparing options for muscle-invasive bladder cancer.

PURPOSE OF REVIEW: This review critically evaluates the current state of bladder-sparing options in muscle-invasive bladder cancer (MIBC) and provides an overview of future directions in the field. RECENT FINDINGS: Bladder-sparing treatments have emerged as viable alternatives to radical cystectomy (RC) for selected patients with MIBC, especially in those who are unfit for RC or elect bladder preservation. Numerous studies have assessed the efficacy of trimodal therapy (TMT), with outcomes comparable to RC in a subgroup of well selected patients. Combining immunotherapy with conventional treatments in bladder-sparing approaches can yield promising outcomes. Current research is making significant progress in optimizing treatment protocols by exploring new combinations of systemic therapy agents, innovative drug delivery methods, and biomarker-based approaches. Furthermore, clinical markers of response are being tested to ensure adequate response assessment. SUMMARY: Bladder preservation promise to offer a viable alternative to RC for selected patients with MIBC with the potential to improve patient quality of life. Careful patient selection and ongoing research are essential to optimize patient selection, response assessment, and salvage strategies. As evidence continues to evolve, the role of bladder preservation in MIBC is likely to expand, providing patients with more treatment options tailored to their needs and preferences.

Cardiovascular events among men with prostate cancer treated with androgen receptor signaling inhibitors: a systematic review, meta-analysis, and network meta-analysis.

BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.

A novel assessment of whole-mount Gleason grading in prostate cancer to identify candidates for radical prostatectomy: a machine learning-based multiomics study.

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment. Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent 68Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics features from whole exome sequencing, and pathomics features derived from immunohistochemical staining of 11 biomarkers. Based on the multiomics dataset, five ML models were established and validated using 100-fold Monte Carlo cross-validation. Results: Among five ML models, the random forest (RF) model performed best in terms of the area under the curve (AUC). Compared to bxGG assessment alone, the RF model was superior in terms of AUC (0.87 vs 0.75), specificity (0.72 vs 0.61), positive predictive value (0.79 vs 0.75), and accuracy (0.78 vs 0.77) and showed slightly decreased sensitivity (0.83 vs 0.89) and negative predictive value (0.80 vs 0.81). Among the feature categories, bxGG was identified as the most important feature, followed by pathomics, clinical, radiomics and genomics features. The three important individual features were bxGG, PSA staining and one intensity-related radiomics feature. Conclusion: The findings demonstrate a superior assessment of the developed multiomics-based ML model in whole-mount GG compared to the current clinical baseline of bxGG. This enables personalized patient management by identifying high-risk PCa patients for RP.

Adverse In-Hospital Outcomes after Radical Prostatectomy in Leukemia History Patients.

INTRODUCTION: Leukemia history affects some radical prostatectomy (RP) patients. Although its prevalence and effect as an adverse risk factor are well known in cardiac surgery, the number of RP patients with a leukemia history, as well as their rate of adverse in-hospital outcomes, are unknown. METHODS: We identified RP patients (National Inpatient Sample 2000-2019), stratified according to the presence or absence of a leukemia history. Descriptive analyses, propensity score matching (PSM, ratio 1:10), and multivariable logistic regression models were used. RESULTS: Of 259,939 RP patients, 416 (0.2%) had a leukemia history. Their proportion increased from 0.1 to 0.2% covering the study span (p < 0.01). Leukemia history patients were older (median age, 64 vs. 62 years, p < 0.001). After PSM for age, insurance status, ethnicity, pelvic lymph node dissection, and Charlson Comorbidity Index, leukemia history RP patients exhibited higher rates of acute kidney injury (<2.6 vs. 0.9%; Odds Ratio [OR] 2.0, p = 0.02), more frequently underwent dialysis (3.6 vs. 1.9%; OR 1.9, p = 0.03), and more frequently had a length of stay exceeding one week (4.8 vs. 2.5%; OR 2.0, p = 0.006). CONCLUSIONS: Although leukemia history RP patients are rare, their numbers have increased. Renal complications and extended hospital stays are more frequent in those individuals.

Perineal Urethrostomy for Complex Urethral Strictures: Long-Term Patient-Reported Outcomes from a Reconstructive Referral Center and a Scoping Literature Review.

PURPOSE: There is a paucity of long-term objective and patient-reported outcomes after definitive perineal urethrostomy for complex urethral strictures. Our objective is to determine comprehensive long-term success of perineal urethrostomy with our 15-year experience at a reconstructive referral center. MATERIALS AND METHODS: Patients who underwent perineal urethrostomy between 2009 and 2023 were identified. A comprehensive long-term follow-up was conducted, evaluating both objective outcomes (retreatment-free survival) and subjective outcomes through the use of validated questionnaires. Additionally, to provide further context for our findings, we conducted a scoping review of all studies reporting outcomes following perineal urethrostomy. RESULTS: Among 76 patients, 55% had iatrogenic strictures, with 82% previously undergoing urethral interventions. At a median follow-up of 55 months, retreatment-free survival was 84%, with 16% of patients experiencing perineal urethrostomy recurrent stenosis. Patient-reported outcomes revealed a generally satisfactory voiding function (Urethral Stricture Surgery patient-reported outcome measure Lower Urinary Tract Symptoms score) and continence (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form), with median scores of 4 (range 0-24) and 0 (range 0-21), but with bimodal distributions of sexual function scores (median International Index of Erectile Function-Erectile Function domain: 3.5; median Male Sexual Health Questionnaire-Ejaculation Scale: 21). Treatment satisfaction was very high with a median International Consultation on Incontinence Questionnaire-Satisfaction outcome score of 21 (range 0-24). The scoping review revealed varying success rates ranging from 51% to 95%, highlighting difficulties in comparison due to variable success definitions and patient case mix. CONCLUSIONS: Perineal urethrostomy provides effective treatment for complex anterior urethral strictures, with high patient satisfaction, preserved continence function, and favorable voiding outcomes. It presents a viable option for older and comorbid patients, especially after thorough counseling on expected outcomes and potential risks.

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.

Evidence and emerging trends in local therapy for metastatic hormone-sensitive prostate cancer: a narrative review.

Introduction: Metastatic hormone-sensitive prostate cancer (mHSPC) displays both simultaneous and sequential patterns of metastasis, emphasizing a comprehensive treatment approach that integrates both local therapy and systemic treatment strategies. The increasing use of molecular imaging has led to a rise in mHSPC diagnoses, underscoring the importance of identifying the right patient population and effective treatment concepts for this disease state. Results: Two prospective trials, HORRAD and STAMP EDE, investigated prostate radiotherapy (RT) for mHSPC; however, they did not show an overall survival (OS) benefit in the unselected cohort. Nonetheless, RT showed favorable outcomes in patients with fewer than five bone metastases, resulting in a 7% 3-year survival improvement and supporting the integration of RT in multimodal treatment for men with oligometastatic mHSPC. Regarding cytoreductive prostatectomy (cRP), the TRoMbone Trial confirmed its feasibility and safety. In addition, findings from the FUSCC-OMPCa Trial demonstrated improved 3-year radiographic progression-free survival and OS rates with acceptable rates of complications and incontinence. Recent data from the LoMP registry have further supported superior OS and cancer-specific survival (CSS) in patients undergoing cRP compared to systemic therapy alone. Notably, no significant differences in OS and CSS were observed between the cRP and RT groups. However, cRP-treated patients exhibited superior 2-year local event-free survival when compared to those treated with RT. Conclusion: RT in combination with systemic therapy remains the established first-line treatment for low-burden mHSPC, though the exact definition of low metastatic burden remains contentious. Precise assessment of metastatic burden is vital to identify patients who would derive the greatest benefit from RT. As treatment paradigms evolve, embracing multimodal approaches holds potential for optimizing outcomes in patients with mHSPC. Further research is needed to solidify the role of cRP as a standard therapeutic approach and to refine treatment strategies for improved patient outcomes.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Prostate Biopsy: A Systematic Review and Meta-analysis of Prospective Studies.

BACKGROUND AND OBJECTIVE: The benefits of the detection of clinically significant prostate cancer (csPCa) and safety of magnetic resonance imaging (MRI)-targeted transperineal (TP) prostate biopsy (TP-Tbx) versus transrectal (TR) approaches are still a matter of debate. This review aims to compare the efficacy and safety of TP-Tbx and MRI-targeted TR biopsy (TR-Tbx). METHODS: A systematic literature search was performed in PubMed/Medline, Scopus, and Web of Science to identify records of prospective randomized controlled trials (RCTs) comparing TP-Tbx and TR-Tbx published until May 2024. The primary outcomes included detection rates of csPCa (International Society of Urological Pathology [ISUP] ≥2) and rates of complications. KEY FINDINGS AND LIMITATIONS: Three RCTs (PREVENT, ProBE-PC, and PERFECT) met the inclusion criteria. The TR technique was commonly administered with antibiotic prophylaxis to mitigate infection risks or after a rectal swab. No difference was found between TP-Tbx and TR-Tbx in terms of either csPCa (odds ratio [OR] 0.9, 95% confidence interval [CI]: 0.7-1.1) or ISUP 1 prostate cancer (PCa; OR 1.1, 95% CI: 0.8-1.4) detection. Postprocedural infection (OR 0.8, 95% CI: 0.4-1.8), sepsis (OR 0.6, 95% CI: 0.1-4.5), and urinary retention rates (OR 0.5, 95% CI: 0.1-1.6) were similar. Pain during the TP approach was slightly higher than during the TR approach, but after 7 d of follow-up, the differences between the two approaches were minimal. Variations in biopsy numbers per patient, patient selection, use of 5-alpha reductase inhibitors, needle sizes, TP techniques, and pain scores (reported in only one RCT), along with the multicenter nature of RCTs, limit the study. CONCLUSIONS AND CLINICAL IMPLICATIONS: TP-Tbx and TR-Tbx show similar results in detecting PCa, with comparable rates of infections, urinary retention, and effectiveness in managing biopsy-associated pain. TP-Tbx can safely omit antibiotics without increasing infection risk, unlike TR-Tbx. The tendency to exclude from practice TR-Tbx with prophylactic antibiotics due to infection concerns could be moderated; however, the directionality of some key outcomes, as infections and sepsis, favor the TP approach despite a lack of statistical significance. PATIENT SUMMARY: There were no significant differences in the prostate biopsy approaches (transperineal [TP] vs transrectal [TR]) for prostate cancer detection and complications. However, the MRI-targeted TP prostate biopsy approach may be advantageous as it can be performed safely without antibiotics, potentially reducing antibiotic resistance.

Artificial intelligence for predicting response to neoadjuvant chemotherapy for bladder cancer: A comprehensive systematic review and meta-analysis.

INTRODUCTION: Neoadjuvant cisplatinbased combination chemotherapy (NAC) followed by radical cystectomy is the standard of care for cisplatin-fit patients harboring muscle-invasive bladder cancer (MIBC). Prediction of response to NAC is essential for clinical decision-making regarding alternatives in case of non-response and bladder-sparing in case of complete response. This research aimed to assess the performance of machine learning in predicting therapeutic response following NAC treatment in patients with MIBC. METHODS: A systematic review adhering to the PRISMA guidelines was conducted until July 2023. The study integrated articles relating to artificial intelligence and NAC response in MIBC from various databases. The quality of articles was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 (QUADAS-2). A meta-analysis was subsequently performed on selected studies to determine the sensitivity and specificity of machine learning algorithms in predicting NAC response. RESULTS: Of 655 articles identified, 12 studies comprising 1523 patients were included, and four studies were eligible for meta-analysis. The sensitivity and specificity of the studies were 0.62 (95% confidence interval [CI] 0.50-0.72) and 0.82 (95% CI 0.72-0.89), respectively, with a heterogeneity score (I2) of 38.5%. The machine learning algorithms used computed tomography, genetic, and anatomopathological data as input and exhibited promising potential for predicting NAC response. CONCLUSIONS: Machine-learning algorithms, especially those using computed tomography, genetic, and pathologic data, demonstrate significant potential for predicting NAC response in MIBC. Standardization of methodologic data analysis and response criteria are needed as validation studies.

The association of type and number of high-risk criteria with cancer-specific mortality in prostate cancer patients treated with radical prostatectomy.

Objectives: This study aimed to test the association between of type and number of D'Amico high-risk criteria (DHRCs) with cancer-specific mortality (CSM) in high-risk prostate cancer patients treated with radical prostatectomy. Materials and methods: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 31,281 radical prostatectomy patients with at least 1 DHRC, namely, prostate-specific antigen (PSA) >20 ng/mL (hrPSA), biopsy Gleason Grade Group (hrGGG) score of 4 and 5, or clinical tumor stage ≥T3 (hrcT). Multivariable Cox regression models and competing risks regression models (adjusting for other cause mortality) tested the association between DHRCs and 5-year CSM. Results: Of 31,281 patients, 14,394 (67%) exclusively harbored hrGGG, 3189 (15%) harbored hrPSA, and 1781 (8.2%) harbored hrcT. Only 2132 patients (6.8%) harbored a combination of the 2 DHRCs, and 138 (0.6%) had all 3 DHRCs. Five-year CSM rates ranged from 0.9% to 3.0% when any individual DHRC was present (hrcT, hrPSA, and hrGGG, in that order), 1.6% to 5.9% when 2 DHRCs were present (hrPSA-hrcT, hrcT-hrGGG, and hrPSA-hrGGG, in that order), and 8.1% when all 3 DHRCs were present. Cox regression models and competing risks regression confirmed the independent predictor status of DHRCs for 5-year CSM that was observed in univariable analyses, with hazard ratios from 1.00 to 2.83 for 1 DHRC, 2.35 to 5.88 for combinations of 2 DHRCs, and 7.13 for all 3 DHRCs. Conclusions: Within individual DHRCs, hrcT and hrPSA exhibited weaker effects than hrGGG did. Moreover, a dose-response effect was identified according to the number of DHRCs. Accordingly, the type and number of DHRCs allow further risk stratification within the high-risk subgroup.

Effect of race/ethnicity on survival in surgically treated intermediate/high risk non-metastatic clear cell renal carcinoma.

PURPOSE: It is unknown to what extent 10-year overall survival of radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients differs from age- and sex-matched population-based controls, especially when race/ethnicity is considered (Caucasian vs. African American vs. Hispanic vs. Asian/Pacific Islander). METHODS: We relied on the SEER database (2004-2018) to identify newly diagnosed radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients. For each case, we simulated an age- and sex-matched control relying on Social Security Administration Life Tables with 10 years of follow-up. We compared overall survival between renal carcinoma cases and population-based controls. Multivariable competing risks regression models tested for predictors of cancer-specific mortality versus other-cause mortality. RESULTS: Of 6877 radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients, 5050 (73%) were Caucasian versus 433 (6%) African American versus 1002 (15%) Hispanic versus 392 (6%) Asian/Pacific Islanders. At 10 years, overall survival difference between radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients versus population-based controls was greatest in African Americans (51% vs. 81%, Δ = 30%), followed by Hispanics (54% vs. 80%, Δ = 26%), Asian/Pacific Islanders (56% vs. 80%, Δ = 24%) and Caucasians (52% vs. 74%, Δ = 22%). In competing risks regression, only African Americans exhibited significantly higher other cause mortality (hazard ratio = 1.3; 95% confidence interval = 1.1 - 1.6; p = 0.01) than others. CONCLUSION: Relative to Life Tables' derived sex- and age-matched controls, radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients exhibit worse overall survival, with worst overall survival recorded in African Americans of all race/ethnicity groups.

Race/Ethnicity Affects Access and Survival Differences After Neoadjuvant or Adjuvant Chemotherapy at Radical Cystectomy in Urothelial Carcinoma Patients.

INTRODUCTION: It is unknown whether race/ethnicity affects access and/or survival after neoadjuvant (NAC) or adjuvant chemotherapy (ADJ) at radical cystectomy (RC). We addressed these knowledge gaps. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified NAC candidates (T2-T4N0M0) and ADJ candidates (T3-T4 and/or N1-3). We focused on the four most prevalent race/ethnicities: Caucasians, Hispanics, African American (AA), and Asian/Pacific Islanders (API). Multivariable logistic regression models (MLR) tested access to NAC and ADJ. Subsequently, within NAC-exposed patients, survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression models addressed CSM according to race/ethnicity were fitted. We repeated the same methodology in ADJ-exposed patients. RESULTS: In 6418 NAC candidates, NAC was administered in 1011 (19.0%) Caucasians, 88 (21.0%) Hispanics, 65 (17.0%) AA, and 53 (18.0%) API. In MLR, AA exhibited lower access rates to NAC (OR 0.83, p = 0.04). In NAC-exposed patients, AA independently predicted higher CSM (HR 1.3, p < 0.001) and API independently predicted lower CSM (HR 0.83, p = 0.03). Similarly, in 5195 ADJ candidates, ADJ was administered to 1387 (33.0%) Caucasians, 100 (28.0%) Hispanics, 105 (29.0%) AA, and 90 (37.0%) API. In MLR, AA (OR 68, p = 0.003) and Hispanics (OR 0.69, p = 0.004) exhibited lower access rates to ADJ. In ADJ-exposed patients, AA independently predicted lower CSM (HR 1.32, p < 0.001), while API showed better CSM (HR 0.82, p = 0.01). CONCLUSION: Relative to Caucasians, AA are less likely to receive either NAC or ADJ. Moreover, relative to Caucasians, AA exhibit higher CSM even when treated with either NAC or ADJ.

FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies.

In this review, we revisit the pivotal role of fibroblast growth factor receptor 3 (FGFR3) in bladder cancer (BLCA), underscoring its prevalence in both non-muscle-invasive and muscle-invasive forms of the disease. FGFR3 mutations in up to half of BLCAs play a well-established role in tumorigenesis, shaping distinct tumor initiation patterns and impacting the tumor microenvironment (TME). Emphasizing the importance of considering epithelial-mesenchymal transition profile and TME status, we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3-mutated BLCAs. This writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3-mutated BLCA, stressing the pressing need to unravel resistance mechanisms and identify co-targets for future combinatorial studies. A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms, including secondary mutations, epigenetic alterations in pathway effectors, phenotypic heterogeneity, and population-specific variations within FGFR3 mutational status. Lastly, we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3-mutated BLCA.

The effect of adrenalectomy on overall survival in metastatic adrenocortical carcinoma.

CONTEXT: Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown. OBJECTIVE: To assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting. DESIGN AND SETTING: Patients with mACC were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020) and we tested for differences according to adrenalectomy status. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between 2004-2020. INTERVENTION: Primary tumor resection status (Adrenalectomy vs no-adrenalectomy). MAIN OUTCOME AND MEASURES: Kaplan-Meier plots, multivariable Cox regression models and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs. historical (2004-2011), single vs. multiple metastatic sites and assessable specific solitary metastatic sites (lung only and liver only). RESULTS: Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; p<0.001), as well as with three months' landmark analyses (HR: 0.57, p=0.002). The same association effect with three months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49, p<0.001), contemporary patients (HR: 0.57, p=0.004), historical patients (HR: 0.42 , p<0.001), and in those with lung only solitary metastasis (HR: 0.50, p=0.02). In contrast, no significant association was recorded in patients naïve to systemic therapy (HR: 0.68, p=0.3), those with multiple metastatic sites (HR: 0.55, p=0.07) and those with liver only solitary metastasis (HR: 0.98, p=0.9). CONCLUSIONS: The current results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.

Rates of Systemic Therapy for Metastatic Bladder Cancer Are Lower in Unmarried Males and Females.

OBJECTIVE: Systemic therapy is guideline-recommended for metastatic urothelial carcinoma of the urinary bladder (UCUB). Unmarried status represents an important barrier to treatment access in many primaries. The importance of married status is unknown in the context of systemic therapy in metastatic UCUB and was addressed in the current study. METHODS: We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify patients with metastatic UCUB. Univariable and multivariable logistic regression models were fitted to address systemic therapy rates. Additionally, temporal trends were plotted. RESULTS: Overall, 6873 patients with stage IV UCUB were identified. Of those, 4853 (71%) were male. Of males, 2993 (62%) were married vs. 797 (39%) of females. The rates of systemic therapy were 55% in both married males and married females. Married males and females differed from their unmarried counterparts regarding age and race/ethnicity. In males, prior to any adjustment, married status was associated with an odds ratio of 1.46 (P < .001). After adjustment for age and race/ethnicity, the odds ratio increased to 1.73 (P < .001). In females, prior to any adjustment, married status was associated with an odds ratio of 1.94 (P < .001). After adjustment for age and race/ethnicity, the odds ratio decreased to 1.57 (P < .001). CONCLUSION: Unmarried males and unmarried females are significantly exposed to lower access to systemic therapy compared to their married counterparts. In consequence, both unmarried men and unmarried women should be given very careful consideration when use of systemic therapy in metastatic UCUB is contemplated.

Regional Differences in Stage III Nonseminoma Germ Cell Tumor Patients Across SEER Registries.

PURPOSE: We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used. RESULTS: In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004). CONCLUSION: We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management.

European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)-A Summary of the 2024 Guidelines Update.

BACKGROUND AND OBJECTIVE: This publication represents a summary of the updated 2024 European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ. The information presented herein is limited to urothelial carcinoma, unless specified otherwise. The aim is to provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation. METHODS: For the 2024 guidelines on NMIBC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with NMIBC. The guidelines stress the importance of defining patients' risk stratification and treating them appropriately. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into risk factors, diagnosis, classification, prognostic factors, treatment, and follow-up of NMIBC. These guidelines are designed for effective integration into clinical practice.