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 UTUC patients 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 tumour features' differences between groups. RESULTS: Of 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. Both ureteroscopic ablation and segmental resection had similar OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumour 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 tumour locations following segmental resection.

Effect of Focal Zone Size on Treatment Outcomes and Renal Injury Following Extracorporeal Shockwave Lithotripsy of Renal Calculi: A Prospective Randomized Study.

Background: The narrower focal zone (FZ) size of modern lithotripter was considered as one of the factors that resulted in suboptimal treatment result of extracorporeal shockwave lithotripsy (SWL). Therefore, we investigate the efficacy and safety of standard narrow or extended (FZ) sizes in SWL for patients with renal stones. Materials and Methods: In this prospective study conducted between April 2018 and October 2022, patients with renal stones were randomized to receive SWL with either standard or extended FZ. Treatment was delivered using a Modulith SLX-F2 lithotripter with a maximum of 3000 shocks at 1.5 Hz. The primary outcome was treatment success 12 weeks after a single SWL session, defined as the absence of a stone or stone fragment <4 mm on computed tomography. Secondary outcomes included the incidence of perinephric hematoma, stone-free rate (SFR), and changes in the urinary levels of acute renal injury markers. Results: A total of 320 patients were recruited, and 276 patients were randomized into the two groups. The two groups had similar baseline parameters. The treatment success rate was significantly better for standard FZ (74.3%) than the extended FZ group (59.3%) (p = 0.009). Standard FZ also had a significantly better SFR (Grade-A, 36.8% vs 23.0%, p = 0.013) and less pain after treatment. Both groups had similar perinephric hematoma formation rates, unplanned hospital admission rates, and changes in urinary acute renal injury markers. Conclusions: The standard narrow FZ has better treatment efficacy and similar safety compared with the extended FZ during SWL for renal stones. This clinical trial has been registered in the public domain (CCRBCTR) under trial number CUHK_CCRB00510.

High-power holmium laser versus thulium fiber laser for endoscopic enucleation of the prostate in patients with glands larger than 80 ml: Results from the Prostate Endoscopic EnucLeation study group.

Background: Endoscopic enucleation of the prostate (EEP) has gained acceptance as an equitable alternative to transurethral resection of the prostate for benign prostate hyperplasia (BPH). Our primary aim is to compare peri-operative outcomes of EEP using thulium fiber laser (TFL) against high-power holmium laser (HPHL) in hands of experienced surgeons for large prostates (≥80 ml in volume). Secondary outcomes were assess complications within 1 year of follow up. Materials and Methods: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with TFL or HPHL in 13 centers (January 2019-January 2023). Patients with prostate volume ≥80 ml were included, while those with concomitant prostate cancer, previous prostate/urethral surgery, and pelvic radiotherapy were excluded. Results: Of 1,929 included patients, HPHL was utilized in 1,459 and TFL in 470. After propensity score matching (PSM) for baseline characteristics, 247 patients from each group were analyzed. Overall operative time (90 [70, 120] vs. 52.5 [39, 93] min, P < 0.001) and enucleation time (90 [70, 105] vs. 38 [25, 70] min, P < 0.001) were longer in the TFL group, with comparable morcellation time (13 [10, 19.5] vs. 13 [10, 16.5] min, P = 0.914). In terms of postoperative outcomes, there were no differences in 30-day complications such as acute urinary retention, urinary tract infection or sepsis. In the PSM cohort, univariable analyses showed that higher age, lower preoperative Qmax, higher preoperative PVRU, and longer operation time were associated with higher odds of postoperative incontinence, while 2-lobe enucleation had lower odds of incontinence compared to 3-lobe enucleation. Conclusions: This real-world study reaffirms that HPHL and TFL in large prostates are equally efficacious in terms of 30-day complications. TFL with the en-bloc technique has a shorter operative time which significantly improves short- and medium-term functional outcomes.

Urine cytology in the detection of renal cell carcinomas - a territory-wide multi-institutional retrospective review of more than 2 decades.

INTRODUCTION: Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi-institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas. METHODS: Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior. Patient demographics, specimen descriptors, and histology and staging parameters were reviewed and compared against cytologic diagnoses. RESULTS: There were 1147 cases of urine cytology matched with renal cell carcinomas, with 666 renal urothelial/squamous carcinomas for comparison. The detection rate for urothelial/squamous (atypia or above [C3+]: 63.1%; suspicious or above [C4+]: 24.0%) were higher than renal cell carcinoma (C3+: 13.1%; C4+: 1.5%) (p < 0.001). The positive rate for upper tract urine exceeded other collection methods at 45.0% (C3+) and 10.0% (C4+) (p < .01). Other factors associated with increased positive rates were male sex, collecting duct carcinoma histology, nuclear grade, and renal/sinus involvement (p < .05). Multivariate analysis revealed additional positive correlations with presence of sarcomatoid tumor cells, lymphovascular invasion, and perinephric fat involvement (p < .05). Larger lesion size and higher urine volume did not improve detection rates (p < .05). CONCLUSIONS: The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, although urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens.

Risk prediction of bladder cancer among person with diabetes: A derivation and validation study.

AIMS: This study aimed to devise and validate a clinical scoring system for risk prediction of bladder cancer to guide urgent cystoscopy evaluation among people with diabetes. METHODS: People with diabetes who received cystoscopy from a large database in the Chinese population (2009-2018). We recruited a derivation cohort based on random sampling from 70% of all individuals. We used the adjusted odds ratios (aORs) for independent risk factors to devise a risk score, ranging from 0 to 5: 0-2 'average risk' (AR) and 3-5 'high risk' (HR). RESULTS: A total of 5905 people with diabetes, among whom 123 people with BCa were included. The prevalence rate in the derivation (n = 4174) and validation cohorts (n = 1731) was 2.2% and 1.8% respectively. Using the scoring system constructed, 79.6% and 20.4% in the derivation cohort were classified as AR and HR respectively. The prevalence rate in the AR and HR groups was 1.57% and 4.58% respectively. The risk score consisted of age (18-70: 0; >70: 2), male sex (1), ever/ex-smoker (1) and duration of diabetes (≥10 years: 1). Individuals in the HR group had 3.26-fold (95% CI = 1.65-6.44, p = 0.025) increased prevalence of bladder than the AR group. The concordance (c-) statistics was 0.72, implying a good discriminatory capability of the risk score to stratify high-risk individuals who should consider earlier cystoscopy. CONCLUSIONS: The risk prediction algorithm may inform urgency of cystoscopy appointments, thus allowing a more efficient use of resources and contributing to early detection of BCa among people planned to be referred.

Awareness and Use of ChatGPT and Large Language Models: A Prospective Cross-sectional Global Survey in Urology.

BACKGROUND: Since its release in November 2022, ChatGPT has captivated society and shown potential for various aspects of health care. OBJECTIVE: To investigate potential use of ChatGPT, a large language model (LLM), in urology by gathering opinions from urologists worldwide. DESIGN, SETTING, AND PARTICIPANTS: An open web-based survey was distributed via social media and e-mail chains to urologists between April 20, 2023 and May 5, 2023. Participants were asked to answer questions related to their knowledge and experience with artificial intelligence, as well as their opinions of potential use of ChatGPT/LLMs in research and clinical practice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data are reported as the mean and standard deviation for continuous variables, and the frequency and percentage for categorical variables. Charts and tables are used as appropriate, with descriptions of the chart types and the measures used. The data are reported in accordance with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS AND LIMITATIONS: A total of 456 individuals completed the survey (64% completion rate). Nearly half (47.7%) reported that they use ChatGPT/LLMs in their academic practice, with fewer using the technology in clinical practice (19.8%). More than half (62.2%) believe there are potential ethical concerns when using ChatGPT for scientific or academic writing, and 53% reported that they have experienced limitations when using ChatGPT in academic practice. CONCLUSIONS: Urologists recognise the potential of ChatGPT/LLMs in research but have concerns regarding ethics and patient acceptance. There is a desire for regulations and guidelines to ensure appropriate use. In addition, measures should be taken to establish rules and guidelines to maximise safety and efficiency when using this novel technology. PATIENT SUMMARY: A survey asked 456 urologists from around the world about using an artificial intelligence tool called ChatGPT in their work. Almost half of them use ChatGPT for research, but not many use it for patients care. The resonders think ChatGPT could be helpful, but they worry about problems like ethics and want rules to make sure it's used safely.

Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis.

BACKGROUND: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. METHODS: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. RESULTS: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. CONCLUSION: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

Comparing outcomes of thulium fiber laser versus high-power Holmium:YAG laser lithotripsy in pediatric patients managed with RIRS for kidney stones. A multicenter retrospective study.

BACKGROUND: The aim of this study was to evaluate thulium fiber laser (TFL) safety and efficacy compared to high-power (HP) Holmium:YAG laser in pediatric patients who have undergone retrograde intrarenal surgery (RIRS) for kidney stones. METHODS: We retrospectively reviewed data from pediatric patients who underwent RIRS for kidney stones between 2018 and 2020. Complications were assessed 4-6 weeks postoperatively. Stone-free (SF) was defined as the absence of visible fragments or as the presence of a single residual fragment ≤2 mm at 3 months postoperative imaging. Student's t-test for continuous variables, and χ2 and Fisher's Exact Test for categorical variables were used to compare outcomes between patients treated with HP Holmium:YAG (group 1) and TFL (group 2). Univariate (UVA) and multivariate (MVA) logistic regression analyses were performed to predict SF-associated factors. RESULTS: Data from 126 pediatric patients were analyzed, 97 in group 1 and 29 in group 2. Preoperative characteristics were similar between cohorts. No major complication occurred in both groups. Group 2 had a shorter operative time (mean time 49.5 vs. 64.3 min, P=0.024). SF rate was 81.4% and 89.7% (P=0.45) and reintervention rate was 14.4% and 6.89% (P=0.046) in group 1 and 2, respectively. At UVA and MVA, the type of laser did not influence SF rate. However, prestenting and single stones were positively associated with SR rate. CONCLUSIONS: Both laser technologies are safe and effective and showed similar SF rates. TFL showed less operative time and lower re-intervention rate compared to HP Holmium:YAG. Further prospective studies are needed to corroborate our findings.

The impact of body mass index on oncological and surgical outcomes of patients undergoing nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to evaluate the impact of body mass index (BMI) on oncological (primary) and surgical (secondary) outcomes of patients who underwent nephrectomy, as obesity or high BMI is a known risk factor for renal cell carcinoma (RCC) and predictor of poorer outcomes. METHODS: Studies were identified from four electronic databases from database inception to 2 June 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. The review protocol was registered in the International Prospective Register of Systematic Reviews with the identification number: CRD42021275124. RESULTS: A total of 18 studies containing 13 865 patients were identified for the final meta-analysis. Regarding oncological outcomes, higher BMI predicted higher overall survival (BMI >25 vs BMI <25 kg/m2 : hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58-0.85), cancer-specific survival (BMI >25 vs BMI <25 kg/m2 : HR 0.60, 95% CI 0.50-0.73; BMI 25-30 vs BMI <25 kg/m2 : HR 0.46, 95% CI 0.23-0.95; BMI >30 vs BMI <25 kg/m2 : HR 0.50, 95% CI 0.36-0.69), and recurrence-free survival rates (BMI >25 vs BMI <25 kg/m2 : HR 0.72, 95% CI 0.63-0.82; BMI 25-30 vs BMI <25 kg/m2 : HR 0.59, 95% CI 0.42-0.82). Those with a lower BMI fared better in surgical outcomes, such as operation time and warm ischaemic time, although the absolute difference was minimal and unlikely to be clinically significant. There was no difference between groups for length of hospital stay, intraoperative or postoperative complications, blood transfusion requirements, and conversion to open surgery. CONCLUSION: Our study suggests that a higher BMI is associated with improved long-term oncological survival and similar perioperative outcomes as a lower BMI. More research into the underlying biological and physiological mechanisms will enable better understanding of the effect of BMI, beyond mere association, on post-nephrectomy outcomes.

Carboplatin Induction Chemotherapy in Clinically Lymph Node-positive Bladder Cancer.

Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node-positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design setting and participants: This was an observational study of 369 patients with cT2-4 N1-3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9-69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26-57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

A systematic review and meta-analysis of artificial intelligence diagnostic accuracy in prostate cancer histology identification and grading.

BACKGROUND: Artificial intelligence (AI) is a promising tool in pathology, including cancer diagnosis, subtyping, grading, and prognostic prediction. METHODS: The aim of the study is to assess AI application in prostate cancer (PCa) histology. We carried out a systematic literature search in 3 databases. Primary outcome was AI accuracy in differentiating between PCa and benign hyperplasia. Secondary outcomes were AI accuracy in determining Gleason grade and agreement among AI and pathologists. RESULTS: Our final sample consists of 24 studies conducted from 2007 to 2021. They aggregate data from roughly 8000 cases of prostate biopsy and 458 cases of radical prostatectomy (RP). Sensitivity for PCa diagnostic exceeded 90% and ranged from 87% to 100%, and specificity varied from 68% to 99%. Overall accuracy ranged from 83.7% to 98.3% with AUC reaching 0.99. The meta-analysis using the Mantel-Haenszel method showed pooled sensitivity of 0.96 with I2 = 80.7% and pooled specificity of 0.95 with I2 = 86.1%. Pooled positive likehood ratio was 15.3 with I2 = 87.3% and negative - was 0.04 with I2 = 78.6%. SROC (symmetric receiver operating characteristics) curve represents AUC = 0.99. For grading the accuracy of AI was lower: sensitivity for Gleason grading ranged from 77% to 87%, and specificity from 82% to 90%. CONCLUSIONS: The accuracy of AI for PCa identification and grading is comparable to expert pathologists. This is a promising approach which has several possible clinical applications resulting in expedite and optimize pathology reports. AI introduction into common practice may be limited by difficult and time-consuming convolutional neural network training and tuning.

Fragmentation landscape of cell-free DNA revealed by deconvolutional analysis of end motifs.

Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.

Adverse metabolic consequences of androgen deprivation therapy (ADT) on Asian patients with prostate cancer: Primary results from the real-life experience of ADT in Asia (READT) study.

BACKGROUND: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We investigated the relationship between ADT and adverse changes in metabolic parameters in an Asian population. METHODS: This is an international prospective multicenter single-arm cohort yielded from the real-life experience of ADT in Asia (READT) registry. Consecutive ADT-naïve patients diagnosed of PCa and started on ADT were prospectively recruited from 2016 and analyzed. Baseline patient characteristics, PCa disease status, and metabolic parameters were documented. Patients were followed up at 6-month interval for up to 5 years. Metabolic parameters including body weight, lipid profiles, and glycemic profiles were recorded and analyzed. RESULTS: 589 patients were eligible for analysis. ADT was associated with adverse glycemic profiles, being notable at 6 months upon ADT initiation and persisted beyond 1 year. Comparing to baseline, fasting glucose level and hemoglobin A1c level increased by 4.8% (p < 0.001) and 2.7% (p < 0.001), respectively. Triglycerides level was also elevated by 16.1% at 6th month and by 20.6% at 12th month compared to baseline (p < 0.001). Mean body weight was 1.09 kg above baseline at 18th month (p < 0.001). CONCLUSION: ADT was associated with adverse metabolic parameters in terms of glycemic profiles, lipid profiles, and body weight in the Asian population. These changes developed early in the treatment and can persist beyond the first year. Regular monitoring of the biochemical profiles during treatment is paramount in safeguarding the patients' metabolic health.

Thermal ablation vs. active surveillance for renal masses: a systematic review and network meta-analysis.

INTRODUCTION: Partial nephrectomy, thermal ablation and active surveillance are acceptable options for T1 stage renal tumor management. Currently, we lack sufficient information to make an accurate comparison of thermal ablation with active surveillance. The study objectives were to compare thermal ablation with active surveillance indirectly using partial nephrectomy as a reference. EVIDENCE ACQUISITION: We performed a systematic literature search using two databases (Scopus and Medline). The detailed search strategy is available at Prospero, CRD42021290055. The primary outcome was cancer-specific survival. Secondary outcomes included overall survival and metastasis-free survival. EVIDENCE SYNTHESIS: The final sample comprised 33 articles. They included the ones that compare: partial nephrectomy to ablation (29 studies), partial nephrectomy to active surveillance (2 studies), and partial nephrectomy vs. active surveillance vs. ablation (2 articles). We assessed 3-year and 5-year cancer-specific survival, and 3-, 5- and 7-year overall survival. The surface under the cumulative ranking curve (SUCRA) treatment benefit ranking was: cancer-specific survival - 48.6% for thermal ablation and 1.6% for active surveillance (5-year follow-up); overall survival - 52% for thermal ablation and 0.6% for active surveillance (7-year follow-up). The results demonstrated a significantly higher 3-year cancer-specific survival (RR 1.55, P=0.02) and 3- and 7-year follow-up overall survival (RR 1.85, P=0.03) in thermal ablation compared to active surveillance. At 5-year follow-up, cancer-specific survival and overall survival were in favor of thermal ablation while no statistically significant difference was reported. CONCLUSIONS: Thermal ablation offers a significantly higher cancer-specific survival and overall survival at mid-term follow-up in the management of T1 renal tumors compared to active surveillance. However, it is necessary to conduct further prospective randomized studies to validate the data.

Fragmentomics of urinary cell-free DNA in nuclease knockout mouse models.

Urinary cell-free DNA (ucfDNA) is a potential biomarker for bladder cancer detection. However, the biological characteristics of ucfDNA are not well understood. We explored the roles of deoxyribonuclease 1 (DNASE1) and deoxyribonuclease 1-like 3 (DNASE1L3) in the fragmentation of ucfDNA using mouse models. The deletion of Dnase1 in mice (Dnase1-/-) caused aberrations in ucfDNA fragmentation, including a 24-fold increase in DNA concentration, and a 3-fold enrichment of long DNA molecules, with a relative decrease of fragments with thymine ends and reduction of jaggedness (i.e., the presence of single-stranded protruding ends). In contrast, such changes were not observed in mice with Dnase1l3 deletion (Dnase1l3-/-). These results suggested that DNASE1 was an important nuclease contributing to the ucfDNA fragmentation. Western blot analysis revealed that the concentration of DNASE1 protein was higher in urine than DNASE1L3. The native-polyacrylamide gel electrophoresis zymogram showed that DNASE1 activity in urine was higher than that in plasma. Furthermore, the proportion of ucfDNA fragment ends within DNase I hypersensitive sites (DHSs) was significantly increased in Dnase1-deficient mice. In humans, patients with bladder cancer had lower proportions of ucfDNA fragment ends within the DHSs when compared with participants without bladder cancer. The area under the curve (AUC) for differentiating patients with and without bladder cancer was 0.83, suggesting the analysis of ucfDNA fragmentation in the DHSs may have potential for bladder cancer detection. This work revealed the intrinsic links between the nucleases in urine and ucfDNA fragmentomics.

Comparative Outcomes of Primary Versus Recurrent High-risk Non-muscle-invasive and Primary Versus Secondary Muscle-invasive Bladder Cancer After Radical Cystectomy: Results from a Retrospective Multicenter Study.

Background: Radical cystectomy (RC) is indicated in primary or secondary muscle-invasive bladder cancer (primMIBC, secMIBC) and in primary or recurrent high- or very high-risk non-muscle-invasive bladder cancer (primHR-NMIBC, recHR-NMIBC). The optimal timing for RC along the disease spectrum of nonmetastatic urothelial carcinoma remains unclear. Objective: To compare outcomes after RC between patients with primHR-NMIBC, recHR-NMIBC, primMIBC, and secMIBC. Design setting and participants: This retrospective, multicenter study included patients with clinically nonmetastatic bladder cancer (BC) treated with RC. Outcome measurements and statistical analysis: We assessed oncological outcomes for patients who underwent RC according to the natural history of their BC. primHR-NMIBC and primMIBC were defined as no prior history of BC, and recHR-NMIBC and secMIBC as previously treated NMIBC that recurred or progressed to MIBC, respectively. Log-rank analysis was used to compare survival outcomes, and univariable and multivariable Cox and logistic regression analyses were used to identify predictors for survival. Results and limitations: Among the 908 patients included, 211 (23%) had primHR-NMIBC, 125 (14%) had recHR-NMIBC, 404 (44%) had primMIBC, and 168 (19%) had secMIBC. Lymph node involvement and pathological upstaging were more frequent in the secMIBC group than in the other groups (p < 0.001). The median follow-up was 37 mo. The 5-year recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were 77.9%, 83.2%, and 72.7% in primHR-NMIBC, 60.0%, 59%, and 48.9% in recHR-NMIBC, 60.9%, 64.5%, and 54.8% in primMIBC, and 41.3%, 46.5%, and 39% in secMIBC, respectively, with statistically significant differences across all survival outcomes except between recHR-NMIBC and primMIBC. On multivariable Cox regression, recHR-NMIBC was independently associated with shorter RFS (hazard ratio [HR] 1.64; p = 0.03), CSS (HR 1.79; p = 0.01), and OS (HR 1.45; p = 0.03), and secMIBC was associated with shorter CSS (HR 1.77; p = 0.01) and OS (HR 1.57; p = 0.006). Limitations include the biases inherent to the retrospective study design. Conclusions: Patients with recHR-NMIBC and primHR-MIBC had similar survival outcomes, while those with sec-MIBC had the worst outcomes. Therefore, early radical intervention may be indicated in selected patients, and potentially neoadjuvant systemic therapies in some patients with recHR-NMIBC. Patient summary: We compared cancer outcomes in different bladder cancer scenarios in a large, multinational series of patients who underwent removal of the bladder with curative intent. We found that patients who experienced recurrence of non-muscle-invasive bladder cancer (NMIBC) had similar survival outcomes to those with initial muscle-invasive bladder cancer (MIBC), while patients who experienced progression of NMIBC to MIBC had the worst outcomes. Selected patients with non-muscle-invasive disease may benefit from early radical surgery or from perioperative chemotherapy or immunotherapy.

Technique, outcome and changes in prostate dimensions in patients with urinary retention managed by aquablation.

PURPOSE: This study aimed to investigate the functional and urodynamic outcome of Aquablation in patients with acute urinary retention (AUR) on catheters. METHODS: Men aged 50-70 who failed medical treatment of BPO with AUR failing to wean off urethral catheter were recruited to undergo Aquablation. Individuals were assessed pre-operatively and at 3 and 6 months after surgery. The primary outcome was defined by the success rate of weaning off catheter. Secondary outcomes were measured by a change in prostate size, symptom scores and urodynamic parameters. RESULTS: Twenty patients underwent Aquablation between June 2019 and September 2020. Mean duration of the urethral catheter in-situ was 5.9 ± 4.9 weeks and mean prostate size of the cohort pre-operatively was 60.8 ± 15.8 cc. A second pass Aqaublation treatment was performed in 14 patients. Five patients failed to wean off the catheter on the first attempt after surgery, requiring another attempt 1 week later which were all successful. At 3 months after the operation, a significant reduction in prostate volume was observed (60.8 ± 15.8 cc vs 24.9 ± 10.3 cc, p < 0.001). No change in international index of erectile function (IIEF) was found (baseline: 16.1 ± 5.8; 3-month: 14.9 ± 6.4; p = 0.953). Mean bladder outlet obstruction index was 14.2 ± 23.0 at 6 months upon urodynamic assessment with 75% of patients had a resolution of detrusor overactivity. Reduction in prostate length was found to be more significant than a reduction in width and height after Aquablation (R = 0.693, p = 0.039). CONCLUSION: From the early data of a single centre, Aquablation was shown to provide a consistent improvement in symptoms, uroflowmetry and urodynamic parameters in patient with a urethral catheter. Results from our study suggest that improvement from Aquablation is reproducible in patients with AUR.

Reassessment of the Efficacy of Carboplatin for Metastatic Urothelial Carcinoma in the Era of Immunotherapy: A Systematic Review and Meta-analysis.

CONTEXT: Platinum-based combination chemotherapy is the standard treatment for advanced or metastatic urothelial carcinoma (AMUC). However, data comparing the efficacy of different platinum agents are limited. OBJECTIVE: This review aimed to assess the efficacy of carboplatin as a first-line treatment for AMUC using phase 3 randomized trial data. EVIDENCE ACQUISITION: Multiple databases were searched for articles published until August 2021. Studies that compared overall survival (OS), complete response (CR), and objective response rates (ORRs) in chemotherapy-eligible patients with AMUC were deemed eligible. EVIDENCE SYNTHESIS: Four studies were included. Compared with immune checkpoint inhibitor (ICI) monotherapy, neither cisplatin- nor carboplatin-based chemotherapy was associated with significant OS (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.85-1.11, p = 0.64 and HR: 0.90, 95% CI: 0.78-1.04, p = 0.16, respectively) and CR (odds ratio [OR]: 1.16, 95% CI: 0.70-1.92, p = 0.57 and OR: 0.89, 95% CI: 0.52-1.53, p = 0.67, respectively benefits, while both were associated with a favorable ORR (OR: 0.54, 95% CI: 0.40-0.74, p < 0.001 and OR: 0.58, 95% CI: 0.42-0.80, p < 0.001, respectively). A network meta-analysis (NMA)-based indirect comparison between carboplatin and cisplatin revealed that while cisplatin was slightly better than carboplatin in terms of OS, CR, and ORR, no significant difference was noted. CONCLUSIONS: Cisplatin- and carboplatin-based chemotherapies offer similar OS/CR benefits to ICI monotherapy and elicit a greater ORR than ICI monotherapy. Moreover, our NMA demonstrated that both cisplatin- and carboplatin-based chemotherapy have a similar efficacy in terms of OS, CR, and ORR. Given that carboplatin-based chemotherapy is shown to be more effective in contemporary series than in historical controls, it is strongly recommended that carboplatin be re-examined for its value in the era of ICIs and beyond. PATIENT SUMMARY: Cisplatin- as well as carboplatin-based chemotherapy is as effective as immune checkpoint inhibitors in terms of survival and eliciting a positive response. It is currently believed that cisplatin provides greater benefits than carboplatin; this requires re-evaluation.