PiRNA-4447944 promotes castration-resistant growth and metastasis of prostate cancer by inhibiting NEFH expression through forming the piRNA-4447944-PIWIL2-NEFH complex.

Castration-resistant prostate cancer (CRPC) is the leading cause of prostate cancer (PCa)-related death in males, which occurs after the failure of androgen deprivation therapy (ADT). PIWI-interacting RNAs (piRNAs) are crucial regulators in many human cancers, but their expression patterns and roles in CRPC remain unknown. In this study, we performed small RNA sequencing to explore CRPC-associated piRNAs using 10 benign prostate tissues, and 9 paired hormone-sensitive PCa (HSPCa) and CRPC tissues from the same patients. PiRNA-4447944 (piR-4447944) was discovered to be highly expressed in CRPC group compared with HSPCa and benign groups. Functional analyses revealed that piR-4447944 overexpression endowed PCa cells with castration resistance ability in vitro and in vivo, whereas knockdown of piR-4447944 using anti-sense RNA suppressed the proliferation, migration and invasion of CRPC cells. Additionally, enforced piR-4447944 expression promoted in vitro migration and invasion of PCa cells, and reduced cell apoptosis. Mechanistically, piR-4447944 bound to PIWIL2 to form a piR-4447944/PIWIL2 complex and inhibited tumor suppressor NEFH through direct interaction at the post-transcriptional level. Collectively, our study indicates that piR-4447944 is essential for prostate tumor-propagating cells and mediates androgen-independent growth of PCa, which extends current understanding of piRNAs in cancer biology and provides a potential approach for CRPC treatment.

Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

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.

A 2-year prospective evaluation of the Prostate Health Index in guiding biopsy decisions in a large cohort.

OBJECTIVES: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. PATIENTS AND METHODS: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. RESULTS: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow-up of 2.4 years. CONCLUSION: In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.

Outcomes and considerations for retrograde intrarenal surgery (RIRS) in the setting of multiple and large renal stones (>15 mm) in children: Findings from multicentre and real-world setting.

Purpose: The aim of this study is to evaluate the outcomes of retrograde intra renal surgery (RIRS) in the setting of large or multiple stones in children (<18 years). Materials and Methods: Retrospective analysis was performed of paediatric RIRS cases at nine centres worldwide over a 6-year period. Patients were divided into two groups: Group 1 had a single stone <15 mm. Group 2 had either multiple stones, maximum stone diameter of >15 mm, or both. Outcomes included stone free rate (SFR) and complications within 30 days. Results: In total, 344 patients were included with 197 and 147 in Groups 1 and 2, respectively. Ureteric access sheaths were more frequently used in Group 2 (39.5% vs. 56.8%, p = 0.021). The operation time was significantly longer in Group 2 (p < 0.001). SFR after a single procedure was 84.7% in Group 1 and 63.7% in Group 2. Overall complication rates in Groups 1 and 2 were 7.6% and 33.3%, respectively. The most frequently reported complication in both groups was post-operative fever (4.4% vs. 14%, p = 0.004). The rate of Clavien I/II complications in groups 1 and 2 was 6% and 25.1%, respectively (p < 0.05). The rate of Clavien ≥ III complications in groups 1 and 2 was 1.6% and 8.1%, respectively (p < 0.05). On multivariate analysis, total operation time, stone size and multiplicity were significant predictors of residual fragments. Conclusions: RIRS can be performed in paediatric cases with large and multiple stone burdens, but the complication rate is significantly higher when compared to smaller stones.

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.

The establishment of kidney cancer organoid line in drug testing.

INTRODUCTION: Kidney cancer is a common urological malignancy worldwide with an increasing incidence in recent years. Among all subtypes, renal cell carcinoma (RCC) represents the most predominant malignancy in kidney. Clinicians faced a major challenge to select the most effective and suitable treatment regime for patients from a wide range of modalities, despite improved understanding and diagnosis of RCC. OBJECTIVE: Recently, organoid culture gained more interest as the 3D model is shown to be highly patient specific which is hypothetically beneficial to the investigation of precision medicine. Nonetheless, the development and application of organotypic culture in RCC is still immature, therefore, the primary objective of this study was to establish an organoid model for RCC. MATERIALS AND METHODS: Patients diagnosed with renal tumor and underwent surgical intervention were recruited. RCC specimen was collected and derived into organoids. Derived organoids were validated by histological examminations, sequencing and xenograft. Drug response of organoids were compared with resistance cell line and patients' clinical outcomes. RESULTS: Our results demonstrated that organoids could be successfully derived from renal tumor and they exhibited high concordance in terms of immunoexpressional patterns. Sequencing results also depicted concordant mutations of driver genes in both organoids and parental tumor tissues. Critical and novel growth factors were discovered during the establishment of organoid model. Besides, organoids derived from renal tumor exhibited tumorigenic properties in vivo. In addition, organoids recapitulated patient's in vivo drug resistance and served as a platform to predict responsiveness of other therapeutic agents. CONCLUSION: Our RCC organoid model recaptiluated histological and genetic features observed in primary tumors. It also served as a potential platform in drug screening for RCC patients, though future studies are necessary before translating the outcomes into clinical practices.

Preoperative Plasma Insulin-Like Growth Factor-I and Its Binding Proteins-Based Risk Stratification of Patients Treated With Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.

Kidney-Sparing Surgery Has Equivalent Oncological Outcomes to Radical Nephroureterectomy for Ureteral Urothelial Carcinoma.

Introduction and Objective: Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large, prospective international UTUC registry. Methods: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included patients with UTUC who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumor features' differences between groups. Results: Of the 391 patients with ureteral UTUC, 309 (79.0%) received RNU and 82 (21.0%) received KSS by ureteroscopy with laser ablation (n = 28) or segmental resection (n = 54). After PSM, there were no differences in OS (p = 0.525), CSS (p = 0.487), upper tract RFS (p = 0.147), intravesical RFS (p = 0.989), PFS (p = 0.617), and MFS (p = 0.336) between KSS and RNU. There were no significant differences between ureteroscopic ablation and segmental resection in OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumor locations following segmental resection. Conclusions: In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumor locations following segmental resection.

Safety and Efficacy of Immediate Hyperthermic Intravesical Chemotherapy Following Transurethral Resection of Bladder Tumour (I-HIVEC).

The recurrence rate following endoscopic treatment of non-muscle-invasive bladder cancer (NMIBC) remains high. Standard treatment includes intravesical instillation of chemotoxic agents such as mitomycin C (MMC) to reduce recurrence. It is postulated that upfront administration of hyperthermic intravesical MMC (HIVEC) immediately after transurethral resection of bladder tumour (TURBT) may enhance its efficacy, but evidence from human trials is scant. This pilot study explored the safety of immediate intravesical MMC instillation following TURBT using a conductive HIVEC system (Combat BRS). Patients diagnosed with papillary bladder tumours scheduled for TURBT were recruited. Among 29 patients treated with HIVEC, there was minimal additional postoperative morbidity. The majority (79.3%) were discharged after a hospital stay of 1 d, and no patient required bladder irrigation. There were six grade I-II adverse events (20.7%) and one grade III event (3.4%). No recurrences were observed within 3 mo, and the 12-mo recurrence rate was 4.5%. The study findings demonstrate that immediate HIVEC MMC instillation following TURBT is safe. Further research is needed to assess long-term efficacy in comparison to standard cold MMC. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is treated with tumour removal via a telescope inserted into the bladder through the urethra (called TURBT). We tested the safety of treating the bladder with a warm solution of a chemotherapy drug (mitomycin C) immediately after TURBT, as this may prevent tumour recurrence. The treatment was safe and well tolerated. Further trials are needed with more patients and longer follow-up to confirm the results.

Long-Term Outcomes of Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion in Robot-Assisted Radical Cystectomy (RARC): Multicenter Results from the Asian RARC Consortium.

PURPOSE: Robot-assisted radical cystectomy (RARC) has gained traction in the management of muscle invasive bladder cancer. Urinary diversion for RARC was achieved with orthotopic neobladder and ileal conduit. Evidence on the optimal method of urinary diversion was limited. Long-term outcomes were not reported before. This study was designed to compare the perioperative and oncological outcomes of ileal conduit versus orthotopic neobladder cases of nonmetastatic bladder cancer treated with RARC. PATIENTS AND METHODS: The Asian RARC consortium was a multicenter registry involving nine Asian centers. Consecutive patients receiving RARC were included. Cases were divided into the ileal conduit and neobladder groups. Background characteristics, operative details, perioperative outcomes, recurrence information, and survival outcomes were reviewed and compared. Primary outcomes include disease-free and overall survival. Secondary outcomes were perioperative results. Multivariate regression analyses were performed. RESULTS: From 2007 to 2020, 521 patients who underwent radical cystectomy were analyzed. Overall, 314 (60.3%) had ileal conduit and 207 (39.7%) had neobladder. The use of neobladder was found to be protective in terms of disease-free survival [Hazard ratio (HR) = 0.870, p = 0.037] and overall survival (HR = 0.670, p = 0.044) compared with ileal conduit. The difference became statistically nonsignificant after being adjusted in multivariate cox-regression analysis. Moreover, neobladder reconstruction was not associated with increased blood loss, nor additional risk of major complications. CONCLUSIONS: Orthotopic neobladder urinary diversion is not inferior to ileal conduit in terms of perioperative safety profile and long-term oncological outcomes. Further prospective studies are warranted for further investigation.

"Seeing Is Believing": Additive Utility of 68Ga-PSMA-11 PET/CT in Prostate Cancer Diagnosis.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study.

BACKGROUND: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. RESULTS: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. CONCLUSION: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.

Reoperation Rate for Residual/Regrowth Adenoma Following Transurethral Interventions for Benign Prostatic Enlargement: Results from a Systematic Review and Meta-Analysis of Comparative Randomized Studies.

Objective: To perform a systematic review to assess the incidence of reoperation rate for residual/regrowth adenoma after transurethral surgeries for benign prostatic enlargement. Materials and Methods: A systematic literature search was performed on November 12, 2023, using Cochrane Central Register of Controlled Trials, PubMed, and Scopus. We only included randomized studies comparing monopolar (M)/bipolar (B) transurethral resection of the prostate (TURP) vs ablation vs enucleation procedures. Incidence of reoperation was assessed using the Cochran-Mantel-Haenszel Method and reported as risk ratio (RR), 95% confidence interval (CI), and p-values. Statistical significance was set at p < 0.05. Evidence synthesis: Forty-eight studies were included. Six studies compared enucleation vs TURP, 41 ablation vs TURP, and 1 study enucleation vs ablation vs TURP, encompassing 457 patients in enucleation, 2259 in ablation, and 2517 in the TURP group. The pooled incidence of reoperation was 6.2%, 0.7%, 2.3%, and 4.3% after ablation, enucleation, M-TURP, and B-TURP, respectively. Meta-analysis showed that the incidence of reoperation was significantly lower in the enucleation group (RR 0.28, 95% CI 0.10-0.81, p = 0.02), but the difference accounted only in studies with follow-up between 1 and 3 years (RR 0.18, 95% CI 0.04-0.85, p = 0.03). The incidence of reoperation was significantly lower in the enucleation compared with the B-TURP group (RR 0.14, 95% CI 0.03-0.77, p = 0.02). Meta-analysis showed that the incidence of reoperation was significantly higher in the ablation group (RR 1.81, 95% CI 1.33-2.47, p = 0.0002), but there was no difference in studies with follow-up up to 1 year (odds ratio 1.78 95% CI 0.97-3.29, p = 0.06) longer than 5 years (RR 2.02, 95% CI 0.71-5.79, p = 0.19). The incidence of reoperation was significantly higher in the ablation compared with the M-TURP group (RR 1.91, 95% CI 1.44-2.54, p < 0.0001). Conclusions: In mid-term follow-up, reoperation rate for residual/regrowth adenoma was significantly lower after enucleation, although was significantly higher after ablation compared with TURP.

Patient Preference of Apalutamide Versus Enzalutamide for Recurrent or Metastatic Hormone-sensitive Prostate Cancer: An Open-label, Randomized, Crossover Trial.

BACKGROUND AND OBJECTIVE: Treatment preference regarding apalutamide versus enzalutamide in prostate cancer (PCa) and the factors influencing decisions are largely unknown. Our aim was to investigate the preference for apalutamide versus enzalutamide among prostate cancer patients and their physicians and caregivers, and factors influencing their decision. METHODS: This was a prospective, open-label, randomized, crossover trial. Patients with recurrence of localized PCa or with metastatic disease not considered as high-risk or high-volume and on continued androgen deprivation therapy were recruited. All subjects received a trial of two agents, apalutamide (A) and enzalutamide (E), for 12 wk each, with a 5-wk washout period in between. The sequencing of the drugs was randomized. The primary outcome was patient preference for one the drugs, assessed at the end of the study. Other outcomes included factors influencing patient preference, a comparison of side-effect profiles, and patients' quality of life (QoL). Physician and caregiver preferences for the drugs and factors affecting their choice were also assessed. KEY FINDINGS AND LIMITATIONS: A total of 74 patients met the eligibility criteria and were randomized to the A â†’ E or E â†’ A arm. Of these, 66 patients (89.1%; 32 A â†’ E, 34 E â†’ A) completed the study. Baseline characteristics were comparable between the two groups, and ∼90% of the patients had low-volume metastatic disease. After completion of both treatments for 12 wk each, the difference in preference for A over E was 17.8%, with similar trends for preference of A over E among physicians (18.2%) and caregivers (22.4%). Fewer side effect was the most critical factor influencing the preference of patients. Among the side effects, less fatigue was the benefit of A over E most frequently reported. No notable difference in QoL was observed between the two drugs. However, the study was terminated on interim analysis and the results might not be conclusive. CONCLUSIONS: There was a trend for preference of A over E among patients with predominantly low-volume recurrent or metastatic PCa and their physicians and caregivers. Fewer side effects was the most critical factor influencing their choice. PATIENT SUMMARY: Patients with low-volume recurrent or metastatic prostate cancer tended to prefer treatment with apalutamide over enzalutamide. Side effects were the most critical factor influencing treatment preference.

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.

The Utility and Safety of Ureteral Access Sheath During Retrograde Intrarenal Surgery in Children.

OBJECTIVE: To compare retrograde intrarenal surgery (RIRS) with and without ureteral access sheath (UAS) in different pediatric age groups. METHODS: The data of RIRS for kidney stone in children were obtained from 9 institutions. Demographic characteristics of patients and stones, intraoperative and postoperative results were recorded. While analyzing the data, patients who underwent RIRS without UAS (group 1) (n = 195) and RIRS with UAS (group 2) (n = 194) were compared. RESULTS: Group 1 was found to be young, thin, and short (P <.001, P = .021, P <.001), but there was no gender difference and similar symptoms were present except hematuria, which was predominant in group 2 (10.6% vs 17.3%, P <.001). Group 1 had smaller stone diameter (9.91 ± 4.46 vs 11.59 ± 4.85 mm, P = .001), shorter operation time (P = .040), less stenting (35.7% vs 72.7%, P = .003). Re-intervention rates and stone-free rates (SFR) were similar between groups (P = .5 and P = .374). However, group 1 had significantly high re-RIRS (P = .009). SFR had a positive correlation with smaller stone size and thulium fiber laser usage compared to holmium fiber laser (HFL) (P <.001 and P = .020), but multivariate analysis revealed only large stone size as a risk factor for residual fragments (P = .001). CONCLUSION: RIRS can be performed safely in children with and without UAS. In children of smaller size or younger age (<5 years), limited use of UAS was observed. UAS may be of greater utility in stones larger than 1 cm, regardless of the age, and using smaller diameter UAS and ureteroscopes can decrease the complications.

Influence of Early Apical Release on Outcomes in Endoscopic Enucleation of the Prostate: Results From a Multicenter Series of 4392 Patients.

OBJECTIVE: To evaluate outcomes after laser endoscopic enucleation of the prostate (EEP) stratified by whether early apical release (EAR) was performed or not. METHODS: We retrospectively reviewed patients with clinical benign prostatic hyperplasia who underwent EEP with holmium or thulium fiber laser in 8 centers (January 2020-January 2022). EXCLUSION CRITERIA: previous prostate/urethral surgery, prostate cancer, pelvic radiotherapy, concomitant lower urinary tract surgery. One-to-one propensity score-matching was performed between patients with EAR vs no EAR, with covariates including age, prostate volume, diabetes mellitus, hypertension, preoperative indwelling catheter, IPSS, Qmax, enucleation, and laser types. Multivariable logistic regression analyses were performed to evaluate independent predictors of 30-day postoperative complications and urinary incontinence. RESULTS: EAR was performed in 2094 of 4392 included patients. The matched cohort consisted of 787 patients per arm. Total operation time was significantly longer in the EAR group (median 75 vs 67 minutes, P = .004). Early complications were higher in the EAR group (18.6% vs 12.5%, P = .001), while postoperative incontinence rates were similar (14.1% vs 13.1%, P = .61). Multivariable regression analysis showed that 3-lobe enucleation and operation time were significant predictors of postoperative complications; preoperative indwelling catheterization, higher prostate volume, and en-bloc enucleation were associated with higher odds of postoperative incontinence. LIMITATION: retrospective nature. CONCLUSION: Performing EAR during EEP is associated with a greater incidence of early complications, which was mainly driven by higher rates of postoperative hematuria and perioperative transfusion. The risk of postoperative incontinence and its duration are not affected by EAR.

A novel mortality risk score for emphysematous pyelonephritis: A multicenter study of the Global Research in the Emphysematous Pyelonephritis group.

Background: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the kidney and the surrounding tissues associated with considerable mortality. We aimed to formulate a score that classifies the risk of mortality in patients with EPN at hospital admission. Materials and methods: Patients diagnosed with EPN between 2013 and 2020 were retrospectively included. Data from 15 centers (70%) were used to develop the scoring system, and data from 7 centers (30%) were used to validate it. Univariable and multivariable logistic regression analyses were performed to identify independent factors related to mortality. Receiver operating characteristic curve analysis was performed to construct the scoring system and calculate the risk of mortality. A standardized regression coefficient was used to quantify the discriminating power of each factor to convert the individual coefficients into points. The area under the curve was used to quantify the scoring system performance. An 8-point scoring system for the mortality risk was created (range, 0-7). Results: In total, 570 patients were included (400 in the test group and 170 in the validation group). Independent predictors of mortality in the multivariable logistic regression were included in the scoring system: quick Sepsis-related Organ Failure Assessment score ≥2 (2 points), anemia, paranephric gas extension, leukocyte count >22,000/µL, thrombocytopenia, and hyperglycemia (1 point each). The mortality rate was <5% for scores ≤3, 83.3% for scores 6, and 100% for scores 7. The area under the curve was 0.90 (95% confidence interval, 0.84-0.95) for test and 0.91 (95% confidence interval, 0.84-0.97) for the validation group. Conclusions: Our score predicts the risk of mortality in patients with EPN at presentation and may help clinicians identify patients at a higher risk of death.