Prior male sling does not affect outcomes of artificial urinary sphincter.

OBJECTIVE: To investigate the outcomes of artificial urinary sphincter (AUS) placement in patients with post-prostatectomy urinary incontinence (PPUI) with or without a prior male sling. PATIENTS AND METHODS: We performed a retrospective chart review of patients who underwent AUS for PPUI from 2007 to 2022. The primary endpoint was to determine the proportion of patients who achieved social continence, defined as self-reported use of 0-1 pad/day. The secondary endpoints were device failure rates and device failure-free survival. RESULTS: The analysis included 210 patients, with 30 (14.3%) having had prior slings and 180 (85.7%) without prior slings. After AUS insertion, 80.0% of patients with prior slings and 76.7% of those without prior slings achieved continence (0-1 pad/day). There were six (20.0%) and 53 (29.4%) device failures in patients with and without prior slings, respectively. The median device failure-free survival was not reached in patients with prior slings and was 8.9 years in patients without prior slings (P = 0.048). Limitations include retrospective nature and small sample size. CONCLUSIONS: The efficacy and safety of AUS in patients with prior slings are similar to those without. Prior sling is associated with a longer device failure-free survival. AUS remains a viable option in patients who have persistent PPI after prior slings.

The impact of diabetes on overactive bladder presentations and associations with health-seeking behavior in China, South Korea, and Taiwan: Results from a cross-sectional, population-based study.

BACKGROUND: This study aimed to explore the impact of diabetes on overactive bladder (OAB) presentations and related predictors of healthcare-seeking behavior among adults aged ≥ 40 years in China, Taiwan, and South Korea. METHODS: An internet-based survey was conducted to assess the prevalence of diabetes, OAB presentations, and self-perceived urinary symptoms by a multi-national sample of 8284 individuals who completed the survey between June 2, 2015 and July 31, 2015. Independent associations with health-seeking behavior for urinary symptoms were estimated with odds ratio (OR) with 95% confidence interval (95% CI) using multivariate logistic regression. RESULTS: Diabetes was reported in 13.6% of participants and OAB was 20.8%. Diabetic participants were older than non-diabetic participants in both sexes. Participants with diabetes reported a higher rate of OAB (43.1%) and increased bothersome symptoms associated with OAB than those without diabetes. Participants with diabetes (OR, 3.07 [2.39-3.96]], urgent incontinence (OR, 2.38 [1.86-3.03]), frequency (OR, 1.86 [1.45-2.38]), and nocturia (OR, 1.14 [1.05-1.24]) were associated with healthcare-seeking behavior. CONCLUSION: The proportion of diabetic participants with OAB was 2.5-fold higher than those without diabetes. Diabetes, urinary frequency, nocturia, and urgent incontinence are predictors of medical treatment-seeking behavior, but the key symptom of OAB-urgency is not a predictor of treatment-seeking behavior. It is important for clinicians to recognize the interplay between diabetes and OAB and to early identify various bothersome urinary symptoms for better health outcomes in daily practice.

Active Surveillance for Taiwanese Men with Localized Prostate Cancer: Intermediate-Term Outcomes and Predictive Factors.

PURPOSE: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS. MATERIALS AND METHODS: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model. RESULTS: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years). CONCLUSIONS: AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.

Anti-tumor effects of deubiquitinating enzyme inhibitor PR-619 in human chondrosarcoma through reduced cell proliferation and endoplasmic reticulum stress-related apoptosis.

Chondrosarcoma, a treatment-resistant cancer with limited therapeutic options, lacks significant advancements in treatment methods. However, PR-619, a novel inhibitor of deubiquitinating enzymes, has demonstrated anti-tumor effects in various malignancies. This study aimed to investigate the impact of PR-619 on chondrosarcoma both in vitro and in vivo. Two human chondrosarcoma cell lines, SW11353 and JJ012, were utilized. Cell viability was assessed using an MTT assay, while flow cytometry enabled the detection of apoptosis and cell cycle progression. Western blotting analyses were conducted to evaluate apoptosis, cell stress, and endoplasmic reticulum (ER) stress. Furthermore, the in vivo anti-tumor effects of PR-619 were examined using a xenograft mouse model. The results revealed that PR-619 induced cytotoxicity, apoptosis, and cell cycle arrest at the G0/G1 stage by activating caspases, PARP cleavage, and p21. Moreover, PR-619 increased the accumulation of polyubiquitinated proteins and ER stress by activating IRE1, GRP78, caspase-4, CHOP, and other cellular stress responses, including JNK activation. In vivo analysis demonstrated that PR-619 effectively inhibited tumor growth with minimal toxicity in the xenograft mouse model. These findings provide evidence of the anti-tumor effects and induction of cellular and ER stress by PR-619 in human chondrosarcoma, suggesting its potential as a novel therapeutic strategy for in human chondrosarcoma.

Current Surgical Treatment for Neurogenic Lower Urinary Tract Dysfunction in Patients with Chronic Spinal Cord Injury.

This study aimed to present a comprehensive literature review of the efforts of a spinal cord injury workgroup in Taiwan regarding urologic surgery for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI). Surgical procedures should be viewed as a final option for managing patients with SCI who have persistent symptoms and complications that cannot be resolved by other means. Surgeries can be grouped according to their purpose: reducing bladder pressures, reducing urethra resistance, increasing urethra resistance, and urinary diversion. The choice of surgery depends on the type of LUTD based on urodynamic tests. Additionally, cognitive function, hand motility, comorbidities, efficacy of surgery, and related complications should be considered.

Botulinum Toxin A Injection for Autonomic Dysreflexia-Detrusor Injection or Urethral Sphincter Injection?

Spinal cord injuries (SCI) have a profound impact on autonomic systems, sometimes resulting in multi-organ dysfunction, including of the neurogenic bladder. Autonomic dysreflexia (AD) is commonly seen in patients with SCI above T6 when the injured cord develops a deregulated sympathetic reflex, which can be induced by bladder sensation and can cause hypertensive crisis. While intravesical injection of botulinum toxin A (Botox) is a standard therapy for neurogenic detrusor overactivity, the role of Botox for AD has rarely been described. This study reviewed the medical records of SCI patients who reported AD and received either detrusor or urethral sphincter injection with Botox. The primary endpoint is the subjective improvement of AD. The secondary endpoint is a change in videourodynamic parameters before and after Botox injection. A total of 200 patients were enrolled for analysis. There were 125 (62.5%) patients in the detrusor injection group, and 75 (37.5%) in the urethral sphincter injection group. There were 79 (63.2%) patients in the detrusor injection group and 43 (57.3%) in the urethral sphincter injection group reporting moderate or marked improvement. Detrusor injection leads to a greater improvement in AD, probably because of decreased detrusor pressure and increased compliance after Botox injection. Urethral sphincter injection appears to have a modest effect on AD, despite general improvements in the voiding parameters of videourodynamic study.

The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma.

Urothelial carcinoma (UC) comprises the majority of bladder cancers. Standard platinum-based chemotherapy has a response rate of approximately 50%, but drug resistance develops after short-term treatment. Deubiquitinating (DUB) enzyme inhibitors increase protein polyubiquitination and endoplasmic reticulum (ER) stress, which might further suppress cancer stemness and overcome cisplatin resistance. Therefore, we investigated the cytotoxic effect and potential mechanisms of b-AP15 on urothelial carcinoma. Our results revealed that b-AP15 induced ER stress and apoptosis in BFTC905, T24, T24/R (cisplatin-resistant), and RT4 urothelial carcinoma cell lines. Inhibition of the MYC signaling pathway and cancer stemness by b-AP15 was confirmed by RNA sequencing, RT-PCR, immunoblotting, and sphere-forming assays. In the mouse xenograft model, the combination of b-AP15 and cisplatin showed superior therapeutic effects compared with either monotherapy.

Clinical Implications of Nadir Serum Prostate-Specific Antigen Levels After Transurethral Enucleation of the Prostate.

Objective: Prostate-specific antigen levels after transurethral enucleation of the prostate may serve as indicators of residual cancer foci. The objective of this study was to investigate the association between the post-transurethral enucleation of the prostate nadir prostate-specific antigen level and prostate cancer. Materials and Methods: We retrospectively reviewed the data of 428 men who underwent transurethral enucleation of the prostate between March 2015 and April 2021. Based on the following exclusion criteria, we excluded 106 men from our analysis: men with metastatic prostate cancer, incomplete transurethral enucleation of the prostate, and missing prostate-specific antigen or prostate size data. Three hundred and twenty-two patients were finally enrolled in our study. These patients were classified into four groups according to the surgical pathology: benign, transition zone (cancer only in the adenoma or transition zone), peripheral zone, and transition and peripheral zones. The optimal cutoff post-transurethral enucleation of the prostate nadir prostate-specific antigen level that predicted residual prostate cancer was determined using receiver operating characteristic curve analysis. Results: In total, 71 (22.0%) men exhibited prostate cancer (median follow-up, 38.0 months). The benign and combined cancer groups showed similar adenoma removal rates (103.0% and 106.7%, respectively). The median nadir prostate-specific antigen levels after transurethral enucleation of the prostate were 0.76, 0.63, 1.79, and 1.70 ng/ml in the benign, transition zone, peripheral zone, and transition and peripheral zone groups, respectively (p < 0.001), with no difference between the benign and transition zone groups (p = 0.458); this suggested that complete transurethral enucleation of the prostate removed all cancer nests in the adenoma in the transition zone group. Receiver operating characteristic curve analysis showed that nadir prostate-specific antigen ≧1.7 ng/ml predicted residual cancer (area under the curve: 0.787) or cancer with a Gleason score of ≧7 (area under the curve: 0.816) in the remaining prostate. Limitations include the retrospective design and the perioperative peripheral zone biopsy rate. Conclusions: The post-transurethral enucleation of the prostate nadir prostate-specific antigen ≧1.7 ng/ml after complete transurethral enucleation of the prostate can predict significant residual cancer. Prostate cancer patients with low post-transurethral enucleation of the prostate prostate-specific antigen levels can be conservatively managed.

Propensity score matching analysis comparing radical prostatectomy and radiotherapy with androgen deprivation therapy in locally advanced prostate cancer.

To compare clinical outcomes between the use of robotic-assisted laparoscopic radical prostatectomy (RP) and radiotherapy (RT) with long-term androgen deprivation therapy (ADT) in locally advanced prostate cancer (PC), 315 patients with locally advanced PC (clinical T-stage 3/4) were considered for analysis retrospectively. Propensity score-matching at a 1:1 ratio was performed. The median follow-up period was 59.2 months (IQR 39.8-87.4). There were 117 (37.1%) patients in the RP group and 198 (62.9%) patients in the RT group. RT patients were older and had higher PSA at diagnosis, higher Gleason score grade group and more advanced T-stage (all p < 0.001). After propensity score-matching, there were 68 patients in each group. Among locally advanced PC patients, treatment with RP had a higher risk of biochemical recurrence compared to the RT group. In multivariate Cox regression analysis, treatment with RT plus ADT significantly decreased the risk of biochemical failure (HR 0.162, p < 0.001), but there was no significant difference in local recurrence, distant metastasis and overall survival (p = 0.470, p = 0.268 and p = 0.509, respectively). This information supported a clinical benefit in BCR control for patients undergoing RT plus long-term ADT compared to RP.

Performance of urinary biomarkers in differentiating dysfunctional voiding in women with overactive bladder syndrome: a prospective pilot study.

PURPOSE: Dysfunctional voiding (DV) in women is a common disorder that causes bladder outlet obstruction (BOO) and may aggravate overactive bladder (OAB) symptoms. The diagnosis of DV relies on clinical alertness and videourodynamic study (VUDS). In this pilot study, we aimed to explore the diagnostic potential of urinary biomarkers in women with DV. METHODS: Women who visited our institute for the management of OAB were enrolled in this prospective study. Urine samples were collected before treatment and urinary proteins were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Patients with DV and patients with normal tracings were included in the study and control group, respectively. The patients with DV were further divided into two subgroups: those with and those without detrusor overactivity (DO). VUDS parameters and urinary protein levels were compared between each subgroup. RESULTS: A total of 67 women were enrolled. There were 47 patients with VUDS-diagnosed DV and 20 patients in the control group. Urinary 8-OHdG level (32.65 vs. 15.59, p < 0.001) and urinary TNF-α level (1.43 vs. 0.83, p = 0.031) were significantly higher in the DV group, and urinary IL-2 level (0.29 vs. 0.83, p < 0.001) was significantly lower in the DV group. Among the DV patients, urinary PGE2 level was higher in the DO group (240.4 vs 149.6, p = 0.049). CONCLUSIONS: In women with DV, urinary 8-OHdG level is elevated compared to women with normal VUDS. Urinary PGE2 level is elevated in patients with DV and DO. These finding suggests increased reactive-oxidative stress response and detrusor hyperactivity in DV patients. Urinary biomarkers can serve as potential non-invasive diagnostic tools in women with OAB.

Prevalence and impacts of male urinary incontinence on quality of life, mental health, work limitation, and health care seeking in China, Taiwan, and South Korea (LUTS Asia): Results from a cross-sectional, population-based study.

PURPOSE: Male urinary incontinence (UI) is a global health issue associated with bothersome symptoms which affect daily life. This study aims to evaluate the prevalence of male UI in China, Taiwan, and South Korea and to determine if UI is an independent risk factor affecting the health-related quality of life (HRQoL), mental health, work limitations, and healthcare seeking behavior. MATERIALS AND METHODS: A post-hoc analysis was conducted on the LUTS Asia database which was collated from a cross-sectional, population-based internet survey in China, Taiwan, and South Korea. Prevalence of male UI was assessed, and the effect on HRQoL, Hospital Anxiety and Depression Scale (HADS) depression and anxiety scores, work performance, and healthcare seeking behaviors was determined using univariate and multivariate analyses. RESULTS: A total of 4,076 male participants were surveyed. Prevalence of male UI was 17.3%. UI adversely affected the HRQoL in both physical and mental domains. Both multivariate and univariate analyses showed that male UI could be correlated with a negative effect on the HADS anxiety and depression scores. Multivariate analysis suggested that work difficulties were correlated to the presence of UI. Up to 28% of participants who reported urge UI only did not adopt any management measures. CONCLUSIONS: UI is common in men over 40 years and adversely impacts HRQoL. It is an independent risk factor for anxiety and depression and may cause significant work limitations. Despite these negative effects, many men still do not seek any intervention.

Impact of Female Stress Urinary Incontinence on Quality of Life, Mental Health, Work Limitation, and Healthcare Seeking in China, Taiwan, and South Korea (LUTS Asia): Results from a Cross-Sectional, Population-Based Study.

Background: Stress urinary incontinence (SUI) is common among adult women with negative effects on psychosocial well-being, mental health, and health-related quality of life. The purpose of the research is to determine if SUI in women is a factor implicated in changes in health-related quality of life (HRQoL) in both physical and mental health domains and in work difficulties. Methods: Data of women 40 years or older from a cross-sectional, population-based, internet survey were examined post-hoc. The effect of SUI frequency on HRQoL (SF12 score), in physical and mental health domains, was assessed. In addition, multivariate and univariate analyses were used to show the influence of SUI on HADS (Hospital Anxiety and Depression Scale) depression score and HADS anxiety score. The effects of demographic factors and physical ailments and SUI on work difficulties were similarly analyzed using multivariate logistic regression. Results: A total of 4208 women with mean age of 60 were included in the analysis. The more frequent SUI episodes were associated with a greater reduction of HRQoL in both physical and mental health domains. In addition, both multivariate and univariate analyses showed that SUI could be correlated with a negative effect on HADS anxiety score (OR 1.617, CI 1.335-1.958, p=0.000) and HADS depression score (OR 1.263, CI 1.044-1.527, p=0.016). Univariate analyses suggested that work difficulties were correlated with SUI. Available data revealed that many sufferers, including up to 40% of individuals with SUI frequency rating 1 (less than once a month) to 3 (a few times a week), failed to seek treatment. Conclusion: SUI, common in women ≥40 years of age, impairs quality of life in both physical and mental health domains. SUI is an independent risk factor for anxiety and depression and has been linked to significant work dysfunctions. Trial Registration: This study is registered at ClinicalTrials.gov: NCT02618421 (Date of registration: December 1, 2015).

Impacts of nocturia on quality of life, mental health, work limitation, and health care seeking in China, Taiwan and South Korea (LUTS Asia): Results from a cross-sectional, population-based study.

BACKGROUND: While nocturia has been proposed to be related to various systemic diseases and even mortality, there has been little information of the impact of nocturia in other aspects of physical and mental well-being. We evaluated the impact of nocturia on quality of life (QoL), mental health, work limitation, and health-care seeking behavior. METHODS: An internet-based self-administered survey was distributed among individuals aged ≥40 years with the ability to use a computer and to read the local language. Survey questions included demographic details, International Continence Society symptom definitions and the international prostate symptom score. Impact on nocturia on health-related QoL physical and mental health domain, Hospital Anxiety and Depression Scale (HADS) score and Work Limitations Questionnaire (WLQ) measures was evaluated. RESULTS: There were 8284 participants (women, 51%) of whom 34% were aged ≥60 years. Prevalence of nocturia ≥2 was 35% in men and 37% in women. Across both genders, QoL decreased with increasing frequency of nocturia. Besides nocturia, hypertension, presence of neurological disorder, lower urinary tract symptom measures and female gender were also associated with HADS anxiety and depression scores of ≥8. Nocturia significantly impacted work ability across WLQ measures. Though the utilization of prescription medications increased with the increase in frequency of nocturia, it was also noted that up to 30% of participants who reported nocturia frequency of ≥3 did not seek any treatment for their complaints. CONCLUSION: Nocturia significantly affects QoL, work productivity, and mental well-being. However, healthcare utilization remains low and warrants increased awareness and education in the patients, caregivers and physicians.

Outcomes of stratified transurethral resection of bladder tumor: A propensity score-matched analysis.

BACKGROUND/PURPOSE: Several strategies have been reported for improving the integrity of transurethral resection of bladder tumor (TURBT). However, no standard has been established. Stratified TURBT (SR) is one of protocols for TURBT, wherein exophytic tumors are first resected and retrieved, and tumor bases are then resected. In this study, we aimed to evaluate the outcomes of SR in patients with nonmuscle invasive bladder cancer (NMIBC). METHODS: From January 2012 to December 2017, patients newly diagnosed as having NMIBC with a follow-up period of more than 2 years were enrolled and categorized into SR and conventional TURBT (CR) groups. Propensity score matching at a 2:1 ratio was performed. Outcomes were the detrusor muscle sampling rate, recurrence-free survival (RFS), and progression-free survival (PFS). RESULTS: In total, 205 patients were included in our study. The detrusor muscle sampling rate was higher in the SR group (P = 0.043). After propensity score matching, 162 patients were selected for outcome analysis, with 108 and 54 patients undergoing SR and CR, respectively. Compared with the CR group, the SR group showed a lower recurrence rate (P = 0.015) and better RFS in univariate (P = 0.010) and multivariate (P = 0.006) Cox proportional hazards regression. Progression rate and PFS were not significantly different between the two groups. CONCLUSION: SR results in a higher detrusor muscle sampling rate and better disease outcomes. Our findings suggest that SR is a promising strategy for TURBT in patients with NMIBC.

Identifying occult bladder outlet obstruction in women with detrusor-underactivity-like urodynamic profiles.

Voiding dysfunction can result from detrusor underactivity (DU), bladder outlet obstruction (BOO), or both. Conceptually, women with high-pressure low-flow urodynamic profiles are diagnosed with BOO without DU. However, the possibility of BOO is often neglected in women with DU-like (low-pressure low-flow) urodynamic (UDS) profiles. By reviewing the videourodynamic studies (VUDS) of 1678 women, our study identified the key factors suggesting urodynamic BOO (determined by radiographic evidence of obstruction) in women with DU-like UDS profiles (Pdet.Qmax < 20 cmH2O and Qmax < 15 mL/s). In 355 women with DU-like UDS profiles, there were 70 (19.7%) with BOO and 285 (80.3%) without BOO. The BOO group had predominantly obstructive symptoms. The BOO group showed significantly decreased bladder sensation, lower detrusor pressure (Pdet.Qmax), lower flow rate (Qmax), smaller voided volume, and larger post-voiding residual (PVR) compared to the non-BOO group. In multivariate analysis, volume at first sensation, Qmax, PVR, and detrusor overactivity (DO) remained independent factors for BOO. The receiver operating characteristic (ROC) areas for the parameters were largest for PVR (area = 0.786) and Qmax (area = 0.742). The best cut-off points were 220 mL for PVR and 4 mL/s for Qmax. Our findings provide simple indicators for BOO in women with DU.

Outcomes and Prediction Models for Exclusive Prostate Bed Salvage Radiotherapy among Patients with Biochemical Recurrence after Radical Prostatectomy.

BACKGROUND: The addition of androgen-deprivation therapy (ADT) or pelvic radiation to prostate bed salvage radiotherapy (SRT) has been debated for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy. This study aimed to assess the outcomes and propose prediction models for exclusive prostate bed SRT. METHODS: This is a prospective observational cohort study with patients who underwent SRT with a pre-SRT PSA < 1.5 ng/mL after radical prostatectomy. Patients were treated with 70-Gy SRT to the prostate bed exclusively. Kaplan-Meier survival analyses and Cox regression analyses were applied for depicting and predicting BCR-free survival, ADT-free survival, and metastasis-free survival (MFS). Regression-based coefficients were used to develop nomograms. RESULTS: A total of 105 patients were included and 91 patients were eligible. The median follow-up period was 39 months. The 5-year BCR-free survival, ADT-free survival, and MFS were 37%, 50%, and 66%, respectively. Multivariable analysis showed that a pre-SRT PSA < 0.45 ng/mL was the only independent factor associated with longer BCR-free survival (p = 0.034), while a PSA-DT > 8 months had better ADT-free survival (p = 0.008). Patients with a PSA-DT > 8 months showed a 100% MFS and a 43% 5-year absolute benefit in MFS than a PSA-DT ≤ 8 months. All patients with a pre-SRT PSA < 0.45 ng/mL and PSA-DT > 8 months were free from subsequent ADT and any metastasis. CONCLUSIONS: In patients with a PSA < 0.45 ng/mL and PSA-DT > 8 months for post-prostatectomy BCR, prostate bed SRT provided excellent outcomes without the need for concomitant ADT or pelvic radiotherapy.

CDK7 inhibition by THZ1 suppresses cancer stemness in both chemonaïve and chemoresistant urothelial carcinoma via the hedgehog signaling pathway.

Urothelial carcinoma (UC) is the most common type of bladder cancer, with a 5-year survival rate of only 4.6% in metastatic UC. Despite the advances related to immune-checkpoint inhibitor therapy, chemotherapy remains the standard of care for metastatic diseases, with a 50% response rate. The covalent cyclin-dependent kinase 7 (CDK7) inhibitor THZ1 interferes with transcription machinery and is reported to be effective in cancers without targetable mutations. Therefore, we investigated the therapeutic effect of THZ1 on UC and examined possible mechanisms underlying its effects in both chemonaïve and chemosensitive cancers. CDK7 expression is increased in bladder cancer tissues, especially in patients with chemoresistance. THZ1 induced apoptosis and decreased viability in RT4, BFTC905, HT1376, T24, and T24/R UC cell lines. RNA-sequencing, immunoblotting, and sphere-formation assays confirmed that THZ1 suppressed cancer stemness. In the mouse xenograft model, THZ1 suppressed both chemonaïve and chemoresistant tumors. These results indicate that CDK7 inhibition-related cancer stemness suppression is a potential therapeutic strategy for both chemonaïve and chemoresistant UC.

Risk Factors for Primary Failure of Metallic Ureteral Stents: Experience from a Tertiary Center.

Introduction: We provide primary patency rate of metallic ureteral stents in cancer patients and investigate the factors affecting primary patency. Methods: All cancer patients who had received metallic stents for malignant ureteral obstruction between July 2009 and November 2012 in our institute were included. No patients were excluded. Patient profiles, imaging studies, and laboratory data were collected. Patient profiles included age, gender, body height, body weight, body mass index, cancer types, treatment for cancer, response to cancer treatment, methods of stent insertion, and prior ordinary stents. Imaging studies included renal ultrasonography, antegrade pyelography, CT, and MRI. Laboratory data included urinalysis, urine culture, and serum creatinine. Complications were defined according to the Clavien-Dindo classification. Primary patency was defined as a complete resolution or downgrading of hydronephrosis shown by imaging studies or success in the removal of a preexisting nephrostomy tube; otherwise the procedure was considered a primary failure. The primary endpoint was the primary patency rate of the stents. The secondary endpoints were risk factors for primary stent failure. Results: A total of 124 stents were inserted into 96 patients with malignant ureteral obstruction. There were no grade 3/4 complications. The overall primary patency rate was 87.9% (109/124). In univariate analysis, antegrade insertion (OR = 24.15, p-value = 0.0086) and urinary tract cancer (OR = 4.18, p-value = 0.0164) were significantly associated with primary failure. Those with prior ordinary stents (OR = 0.20, p-value = 0.0158) or response to cancer treatment (OR = 0.25, p-value = 0.0228) were associated with stent patency. In multivariate analysis, antegrade insertion (OR = 22.04, p-value = 0.0041) and response to cancer treatment (OR = 0.15, p-value = 0.01081) remained significant factors. Conclusions: In this large cohort of cancer patients requiring urinary diversion to preserve renal function, several factors were associated with the success rate of metallic stents.

Association between low prostate-specific antigen levels and greater disease progression in high-grade locally-advanced prostate cancer.

PURPOSE: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). METHODS: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis: <5.0, 5.0-9.9, and ≥10.0. The patients' related parameters were compared among these groups. RESULTS: The median follow-up period was 33.1 months (IQR: 12.1-48.1). There was no difference in biochemical recurrence (BCR) between the 3 groups (Log-rank test, p = 0.484). We found a higher risk of biochemical recurrence in patients with positive surgical margins (HR: 5.04, 95% CI: 1.64-15.50, p = 0.005). In addition, patients with low iPSA levels (<5.0 ng/mL) had poor radiographic progression-free survival (Log-rank test, p = 0.001) and a higher risk of disease progression (HR: 12.2, 95% CI: 1.18-1260.99, p = 0.036) compared with patients with higher iPSA levels (≥10 ng/mL). CONCLUSION: In patients with high-grade locally-advanced PCa, a low iPSA level was associated with a higher risk of disease progression, but not with biochemical recurrence. In this unique population, serum PSA may not be a reliable marker to detect disease progression. Monitoring of these patients may warrant other biomarkers or imaging.