The detection rate for prostate cancer in systematic and targeted prostate biopsy in biopsy-naive patients, according to the localization of the lesion at the mpMRI: A single-center retrospective observational study.

OBJECTIVE: Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients. MATERIAL AND METHODS: A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy. RESULTS: Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018. CONCLUSION: A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores.

Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

A New Approach for On-Chip Production of Biological Microgels Using Photochemical Cross-Linking.

Photochemical cross-linking is a key step for manufacturing microgels in numerous applications, including drug delivery, tissue engineering, material production, and wound healing. Existing photochemical cross-linking techniques in microfluidic devices rely on UV curing, which can cause cell and DNA damage. We address this challenge by developing a microfluidic workflow for producing microgels using visible light-driven photochemical cross-linking of aqueous droplets dispersed in a continuous oil phase. We report a proof-of-concept to construct microgels from the protein Bovine Serum Albumin (BSA) with [Ru(bpy)3]2+ mediated cross-linking. By controlling the capillary number of the continuous and dispersed phases, the volumetric flow rate, and the photochemical reaction time within the microfluidic tubing, we demonstrate the construction of protein microgels with controllable and uniform dimensions. Our technique can, in principle, be applied to a wide range of different proteins with biological and responsive properties. This work therefore bridges the gap between hydrogel manufacturing using visible light and microfluidic microgel templating, facilitating numerous biomedical applications.

Instant messaging in cancer care.

Instant messaging applications, such as WhatsApp® and Telegram®, have transformed global communication, offering unique business models and minimal user expenses. Unlike traditional SMS, these apps facilitate unlimited, multimedia-rich communication globally, driven by widespread smartphone adoption. This shift not only broadens communication horizons but also enhances privacy compared to conventional voice calls. In healthcare, instant messaging, particularly unidirectional communication, proves impactful, evidenced by trials like TEXT ME and Healthy Text. These studies highlight text messages' efficacy in cardiovascular disease prevention and cancer prevention, demonstrating improved patient outcomes and behavioral changes. Bidirectional communication through instant messaging holds promise in cancer care, facilitating patient-doctor interactions, adverse event management, and medication compliance. Studies on pharmacist-run tele-oncology services and WeChat-based doctor-patient communication showcase positive impacts on chemotherapy monitoring, patient adherence, and overall survival rates. Despite these advantages, challenges arise from the use of widely available apps like WhatsApp and WeChat, including a lack of structure, constant message influx, and potential physician burnout. Innovative solutions, exemplified by the Esperto in chat® platform, introduce structured approaches to doctor-patient communication, addressing financial considerations, scheduling, and maintaining work-life balance for healthcare professionals. In conclusion, while instant messaging revolutionizes healthcare communication, challenges necessitate innovative solutions. Striking a balance between accessibility and safeguarding healthcare professionals' well-being is crucial as the digital transformation of healthcare continues.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Morphology, repulsion, and ordering of red blood cells in viscoelastic flows under confinement.

Red blood cells (RBC), the primary carriers of oxygen in the body, play a crucial role across several biomedical applications, while also being an essential model system of a deformable object in the microfluidics and soft matter fields. However, RBC behavior in viscoelastic liquids, which holds promise in enhancing microfluidic diagnostic applications, remains poorly studied. We here show that using viscoelastic polymer solutions as a suspending carrier causes changes in the clustering and shape of flowing RBC in microfluidic flows when compared to a standard Newtonian suspending liquid. Additionally, when the local RBC concentration increases to a point where hydrodynamic interactions take place, we observe the formation of equally-spaced RBC structures, resembling the viscoelasticity-driven ordered particles observed previously in the literature, thus providing the first experimental evidence of viscoelasticity-driven cell ordering. The observed RBC ordering, unaffected by polymer molecular architecture, persists as long as the surrounding medium exhibits shear-thinning, viscoelastic properties. Complementary numerical simulations reveal that viscoelasticity-induced repulsion between RBCs leads to equidistant structures, with shear-thinning modulating this effect. Our results open the way for the development of new biomedical technologies based on the use of viscoelastic liquids while also clarifying fundamental aspects related to multibody hydrodynamic interactions in viscoelastic microfluidic flows.

Adjuvant immunotherapy in patients with renal cell carcinoma and urothelial carcinoma: A systematic review and network meta-analysis.

Adjuvant immune checkpoint inhibitor therapies have radically altered the treatment landscape for renal cell carcinoma and urothelial carcinoma. However, studies have reported negative data regarding adjuvant immune checkpoint inhibitor therapies. Thus, this study aimed to assess the role of adjuvant immune checkpoint inhibitor therapy for both renal cell carcinoma and urothelial carcinoma. A systematic review and network meta-analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases were searched for articles published as of February 2023. Studies were deemed eligible if they evaluated disease-free survival in patients with renal cell carcinoma and urothelial carcinoma receiving adjuvant immune checkpoint inhibitor therapy. Five studies met the inclusion criteria. In a network meta-analysis, pembrolizumab was shown to be the most effective regimen for patients with renal cell carcinoma, whereas nivolumab was found to be the most effective regimen for patients with urothelial carcinoma. Additionally, these results were consistently observed in a sub-analysis of the T stage. The present analysis provides findings that support the usefulness of adjuvant nivolumab therapy in urothelial carcinoma and adjuvant pembrolizumab therapy in renal cell carcinoma, in agreement with the currently available guidelines. However, the caveat is that the randomized controlled trials included in this analysis differed in important respects despite being similar in study design. Therefore, with these differences in mind, care needs to be taken when selecting patients for these immune checkpoint inhibitor therapies to maximize their benefits.

Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.

Characteristics of recurrent acute urinary retention in BPH patients in the United States: Retrospective analysis of US-based insurance claims database.

PURPOSE: The objective of this study is to analyze characteristics of recurrent acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH), utilizing a population based data set. Also, we sought to report on how AUR was treated, specifically regarding the need and length of catheterization and types of procedures utilized for mitigation. MATERIALS & METHODS: A retrospective observational cohort study was performed using Optum's deidentified Clinformatics® Data Mart Database. We compared two groups, BPH patients with AUR (n = 180,737) and BPH patients without AUR (n = 1,139,760) from January 1, 2003 to December 31, 2017. Also, we analyzed the factors affecting the development of multiple episodes of AUR through age-adjusted multivariate analysis. RESULTS: In contrast to the 47.7% of patients who had a single AUR episode, 33.5% of AUR patients developed 3 or more subsequent episodes of retention. For age matched patients, the risks of additional episodes of retention increase significantly with older age, Caucasian race, diabetes, neurologic conditions, or low income. Overall, the rate of BPH surgery in AUR patients over the study period decreased and the most common procedure was transurethral resection of the prostate. CONCLUSIONS: Risk factors for multiple episodes of AUR included age (60 and older), Caucasian race, lower income socioeconomic status, diabetes, and neurological disorders. Patients with a high probability of developing recurrent episodes of AUR are recommended to receive preemptive BPH medication before such AUR occurrences. Also, more expeditious surgical treatment should be considered rather than temporary catheterization when AUR occurs.

The Risk of Cardiovascular and Cerebrovascular Disease in Men With a History of Priapism.

PURPOSE: Priapism is a debilitating condition that affects sexual function. As a majority of cases are idiopathic, investigators have hypothesized underlying vascular dysfunction which may predispose men to priapism. We sought to determine if men are at risk for other sequelae of vascular dysfunction such as cardiovascular and thromboembolic disease after a priapism event. MATERIALS AND METHODS: Using a large commercial insurance claims data warehouse, we evaluated all men (age ≥20) with a diagnosis of priapism from 2003-2020 and matched them to a cohort of men with other urological disorders of sexual dysfunction (erectile dysfunction, Peyronie's disease, and premature ejaculation). We identified incident disease (cardiovascular disease, heart disease, embolism, thrombosis, cerebrovascular disease) for all cohorts. RESULTS: A total of 10,459 men with priapism were identified and were matched to men with erectile dysfunction, Peyronie's disease, or premature ejaculation. The mean age was 51.1 years old. Men with priapism showed increased incidence of heart disease, both ischemic (HR 1.24, 95% CI 1.09-1.42) and other heart disease (HR 1.24, 95% CI 1.12-1.38) in the years following the priapism diagnosis. Incident cerebrovascular disease was also more likely in men with a history of priapism (HR 1.33, 95% CI 1.15-1.55). Men requiring treatment for ischemic priapism had a higher hazard of cardiovascular and cerebrovascular disease. In addition, men with more priapism episodes had a higher rate of cardiovascular disease and thromboembolic events. CONCLUSIONS: Men with priapism are at increased risk for cardiovascular and cerebrovascular events in the years following a priapism.

Diagnostic Accuracy of Clinical Lymph Node Staging for Upper Tract Urothelial Cancer Patients: A Multicenter, Retrospective, Observational Study.

PURPOSE: Treatment options for the management of upper tract urothelial cancer are based on accurate staging. However, the performance of conventional cross-sectional imaging for clinical lymph node staging (N-staging) remains poorly investigated. This study aims to evaluate the diagnostic accuracy of conventional cross-sectional imaging for upper tract urothelial cancer N-staging. MATERIALS AND METHODS: This study was a multicenter, retrospective, observational study. We included 865 nonmetastatic (M0) upper tract urothelial cancer patients treated with curative intended surgery and lymph node dissection who had been staged with conventional cross-sectional imaging before surgery. We compared clinical (c) and pathological (p) N-staging results to evaluate the concordance of node-positive (N+) and node-negative (N0) disease and calculate cN-staging's diagnostic accuracy. RESULTS: Conventional cross-sectional imaging categorized 750 patients cN0 and 115 cN+. Lymph node dissection categorized 641 patients pN0 and 224 pN+. The cN-stage was pathologically downstaged in 6.8% of patients, upstaged in 19%, and found concordant in 74%. The sensitivity and specificity of cN-staging were 25% (95% CI 20; 31) and 91% (95% CI 88; 93). Positive and negative likelihood ratios were 2.7 (95% CI 2.0; 3.8) and 0.83 (95% CI 0.76; 0.89). The area under the receiver operating characteristics curve (0.58, 95% CI 0.55; 0.61) revealed low diagnostic accuracy. CONCLUSIONS: Conventional cross-sectional imaging had low sensitivity in detecting upper tract urothelial cancer pN+ disease. However, cN+ increased the likelihood of pN+ by almost threefold. Thus, conventional cross-sectional imaging is a rule-in but not a rule-out test. Lymph node dissection should remain the standard during extirpative upper tract urothelial cancer surgery to obtain accurate N-staging. cN+ could be a strong argument for early systemic treatment.

Surgical checklist adherence across urology expertise levels impacts transurethral resection of bladder tumour quality indicators.

OBJECTIVES: To address the association of perioperative surgical checklist across variable surgical expertise with transurethral resection of bladder tumour (TURBT) accuracy and oncological outcomes in non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We relied on our prospective collaborative database of patients treated with TURBT between 2012 and 2017. Surgical experience was stratified into three groups: resident vs young vs expert consultants. The association of surgical experience with detrusor muscle (DM) presence and adherence to the standardised peri-procedural nine-items TURBT checklist was evaluated with logistic regression models. A Cox regression model was used to investigate the association of surgical experience with recurrence-free survival (RFS). RESULTS: A total of 503 patients were available for analysis. TURBT was performed by expert consultants in 265 (52.7%) patients, by young consultants in 149 (29.6%) and by residents in 89 (17.7%). Residents were more likely to have DM in the TURBT specimen than expert consultants (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.99, P = 0.04). Conversely, no differences in DM presence were seen between young vs expert consultants (OR 1.09, 95% CI 0.71-1.70, P = 0.69). The median checklist completion rate was higher for both residents and young consultants when compared to experts' counterparts (56% and 56% vs 44%, P = 0.009). When focusing on patients receiving a second-look TURBT, the persistent disease was associated with resident status (OR 4.24, 95% CI 1.14-17.70, P = 0.037) at initial TURBT. Surgical experience was not associated with 5-years RFS. CONCLUSION: Surgeon's experience in the case of adequate perioperative surgical checklist implementation was inversely associated with the presence of DM in the specimen but directly linked to higher probability of persistent disease at re-TURBT, although no 5-year RFS differences were noted.

Association between priapism and HIV disease and treatment.

BACKGROUND: Priapism, a urologic emergency, has known associations with certain medical conditions. Many cases are idiopathic, suggesting an opportunity to identify novel risk factors. AIM: We sought to identify medical conditions and pharmaceutical treatments that are associated with priapism using data-mining techniques. METHODS: Using deidentified data in a large insurance claims database, we identified all men (age ≥20 years) with a diagnosis of priapism from 2003 to 2020 and matched them to cohorts of men with other diseases of male genitalia: erectile dysfunction, Peyronie disease, and premature ejaculation. All medical diagnoses and prescriptions used prior to first disease diagnosis were examined. Predictors were selected by random forest, and conditional multivariate logistic regressions were applied to assess the risks of each predictor. OUTCOMES: We identified novel relationships of HIV and some HIV treatments with priapism and confirmed existing associations. RESULTS: An overall 10 459 men with priapism were identified and matched 1:1 to the 3 control groups. After multivariable adjustment, men with priapism had high associations of hereditary anemias (odds ratio [OR], 3.99; 95% CI, 2.73-5.82), use of vasodilating agents (OR, 2.45; 95% CI, 2.01-2.98), use of HIV medications (OR, 1.95; 95% CI, 1.36-2.79), and use of antipsychotic medications (OR, 1.90; 95% CI, 1.52-2.38) as compared with erectile dysfunction controls. Similar patterns were noted when compared with premature ejaculation and Peyronie disease controls. CLINICAL IMPLICATIONS: HIV and its treatment are associated with priapism, which may affect patient counseling. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first study to identify risk factors for priapism utilizing machine learning. All men in our series were commercially insured, which limits the generalizability of our findings. CONCLUSION: Using data-mining techniques, we confirmed existing associations with priapism (eg, hemolytic anemias, antipsychotics) and identified novel relationships (eg, HIV disease and treatment).

Use of phosphodiesterase 5 inhibitors is not associated with ocular adverse events.

BACKGROUND: Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). AIM: We investigated the risk for SRD, RVO, and ION in patients using PDE5is. METHODS: We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.0) for this analysis. To estimate overall events risk, Cox proportional hazard models were applied to calculate the hazard ratios (HRs) for erectile dysfunction (ED) diagnosis and the different treatments, adjusting for region, median age, obesity, diabetes mellitus, hyperlipidemia, smoking, hypertension, coronary artery disease, and sleep apnea. Additionally, the same analyses were performed to calculate the HRs for benign prostatic hyperplasia (BPH) diagnosis and the different treatments. OUTCOMES: HRs for SRD, RVO, and ION. RESULTS: In total, 1 938 262 men with an ED diagnosis were observed during the study period. Among them, 615 838 (31.8%) were treated with PDE5is. In total, 2 175 439 men with a BPH diagnosis were observed during the study period. Among them, 175 725 (8.1%) were treated with PDE5is. On adjusted Cox regression analysis, PDE5i use was not associated with SRD, RVO, ION, and any ocular event when compared with ED diagnosis and other ED treatments. Importantly, as the intensity of ED treatment increased, so did the risk of ocular events. In addition, PDE5i use was not associated with SRD and ION when compared with BPH diagnosis and other BPH treatments. In contrast, in patients with BPH, PDE5i use was associated with RVO (HR, 1.14; 95% CI, 1.06-1.23). Importantly, patients with BPH receiving other medical treatment (ie, 5a reductase/alpha blocker; HR, 1.11; 95% CI, 1.06-1.16) or surgical treatment (HR, 1.10; 95% CI, 1.02-1.19) had a higher risk of RVO. CLINICAL IMPLICATIONS: We did not observe any consistent association between PDE5i use and any ocular adverse events (SRD, RVO, and ION). STRENGTHS AND LIMITATIONS: Because we did not have access to the patients' medical records, we recorded outcome definitions using ICD-9 and ICD-10 coding. CONCLUSIONS: Patients using PDE5is for ED or BPH indications did not have an increased risk of ocular events, even when compared with other treatments for ED or BPH.

5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.

BACKGROUND: Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. METHODS: Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. RESULTS: In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2 yr) and longer-term (> 2 yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). CONCLUSIONS: We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.

Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?

PURPOSE: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course. METHODS: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested. RESULTS: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC. CONCLUSION: Combined treatment improved RFS and PFS only in patients with Ta disease.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Bladder-sparing strategies in patients with clinically localized muscle-invasive bladder cancer.

PURPOSE OF REVIEW: Radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). In this context, bladder-sparing strategies (BSS) have been investigated as viable alternatives for patients who are unfit for radical cystectomy or aim to preserve their bladder without compromising oncological outcomes. This review aims to provide the most up-to-date evidence on BSSs as an alternative treatment for patients with MIBC. RECENT FINDINGS: Different studies have highlighted the long-term efficacy of trimodal therapy or chemoradiation protocols. However, due to the lack of randomized controlled trials, there is still a lack of high-level evidence on BSS efficacy as compared to radical cystectomy. Consequently, the adoption of these approaches is still limited. A possible turning point could be represented by the introduction of immunotherapy, as several studies are investigating the potential combination with chemoradiotherapy or radiotherapy alone. Patient selection, together with the implementation of new predictive biomarkers and imaging tools, may improve the efficacy of BSS in the near future. SUMMARY: Radical cystectomy with perioperative chemotherapy remains the gold standard treatment for MIBC patients. Nevertheless, BSS can be considered a viable option in selected patients who desire to preserve their bladder. Further evidence is needed to clearly state the role of BSS in MIBC.

Organ-sparing treatment for T1 and T2 penile cancer: an updated literature review.

PURPOSE OF REVIEW: Penile cancer (PeCa) is an orphan disease due to its rare incidence in high-income countries. Traditional surgical options for clinical T1-2 disease, including partial and total penectomy, can dramatically affect patient's quality of life and mental health status. In selected patients, organ-sparing surgery (OSS) has the potential to remove the primary tumor with comparable oncologic outcomes while maintaining penile length, sexual and urinary function. In this review, we aim to discuss the indications, advantages, and outcomes of various OSSs currently available for men diagnosed with PeCa seeking an organ-preserving option. RECENT FINDINGS: Patient survival largely depends on spotting and treating lymph node metastasis at an early stage. The required surgical and radiotherapy skill sets cannot be expected to be available in all centers. Consequently, patients should be referred to high-volume centers to receive the best available treatments for PeCa. SUMMARY: OSS should be used for small and localized PeCa (T1-T2) as an alternative to partial penectomy to preserve patient's quality of life while maintaining sexual and urinary function and penile aesthetics. Overall, there are different techniques that can be used with different response and recurrence rates. In case of tumor recurrence, partial penectomy or radical penectomy is feasible, without impacting overall survival.