Explainable artificial intelligence-driven prostate cancer screening using exosomal multi-marker based dual-gate FET biosensor.

Prostate Imaging Reporting and Data System (PI-RADS) score, a reporting system of prostate MRI cases, has become a standard prostate cancer (PCa) screening method due to exceptional diagnosis performance. However, PI-RADS 3 lesions are an unmet medical need because PI-RADS provides diagnosis accuracy of only 30-40% at most, accompanied by a high false-positive rate. Here, we propose an explainable artificial intelligence (XAI) based PCa screening system integrating a highly sensitive dual-gate field-effect transistor (DGFET) based multi-marker biosensor for ambiguous lesions identification. This system produces interpretable results by analyzing sensing patterns of three urinary exosomal biomarkers, providing a possibility of an evidence-based prediction from clinicians. In our results, XAI-based PCa screening system showed a high accuracy with an AUC of 0.93 using 102 blinded samples with the non-invasive method. Remarkably, the PCa diagnosis accuracy of patients with PI-RADS 3 was more than twice that of conventional PI-RADS scoring. Our system also provided a reasonable explanation of its decision that TMEM256 biomarker is the leading factor for screening those with PI-RADS 3. Our study implies that XAI can facilitate informed decisions, guided by insights into the significance of visualized multi-biomarkers and clinical factors. The XAI-based sensor system can assist healthcare professionals in providing practical and evidence-based PCa diagnoses.

Pre-Op Hydronephrosis Predicts Outcomes in Patients Receiving Robot-Assisted Radical Cystectomy.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. PATIENTS AND METHODS: This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. RESULTS: From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196-2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173-2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). CONCLUSIONS: The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted.

Modified apical dissection during robot-assisted laparoscopic radical prostatectomy: a systematic review and meta-analysis.

Robot-assisted laparoscopic radical prostatectomy (RALP) has improved patient recovery, but achieving optimal functional outcomes remains a challenge, especially early urinary continence. The Modified Apical Dissection (MAD) technique has been suggested to improve early continence compared to conventional RALP. A comprehensive search of PubMed, Embase, and Cochrane Central databases was conducted to identify studies on MAD from inception to March 2024. The risk of bias was evaluated using the ROBINS-I tool. Primary outcomes assessed included urinary continence, positive surgical margin rate, biochemical recurrence rates, and complication rates. Out of 789 studies screened initially, we selected 8 studies that met our inclusion criteria. Our analysis showed that patients who underwent the MAD technique had a significantly higher likelihood of achieving early urinary continence compared to those undergoing conventional RALP at the initial follow-up (Odds Ratio [OR] = 4.0, 95% CI = 1.87-8.57). This advantage continued at 1 month (OR = 5.44, 95% CI = 2.98-9.92), 3 months (OR = 5.36, 95% CI = 2.26-12.71), and 6 months (OR = 5.18, 95% CI = 1.51-17.75), though no significant difference was noted at 12 months. There were no significant differences in positive surgical margin rate or biochemical recurrence rate between MAD and conventional RALP. The overall complication rate was 10.9% (95% CI = 8.10-14.06), with most complications being classified as minor (Clavien-Dindo I-II). In summary, our meta-analysis suggests that the MAD technique may lead to earlier recovery of urinary continence without compromising oncologic outcomes in patients undergoing RALP. While there are published studies on the outcomes of MAD, only a few have the appropriate design with a comparison group needed for meta-analysis and discussing various endpoints. More randomized controlled trials are necessary, but the current literature still lacks retrospective studies with comparison groups.

Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial.

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 .

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

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

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

Machine learning models for predicting the onset of chronic kidney disease after surgery in patients with renal cell carcinoma.

BACKGROUND: Patients with renal cell carcinoma (RCC) have an elevated risk of chronic kidney disease (CKD) following nephrectomy. Therefore, continuous monitoring and subsequent interventions are necessary. It is recommended to evaluate renal function postoperatively. Therefore, a tool to predict CKD onset is essential for postoperative follow-up and management. METHODS: We constructed a cohort using data from eight tertiary hospitals from the Korean Renal Cell Carcinoma (KORCC) database. A dataset of 4389 patients with RCC was constructed for analysis from the collected data. Nine machine learning (ML) models were used to classify the occurrence and nonoccurrence of CKD after surgery. The final model was selected based on the area under the receiver operating characteristic (AUROC), and the importance of the variables constituting the model was confirmed using the shapley additive explanation (SHAP) value and Kaplan-Meier survival analyses. RESULTS: The gradient boost algorithm was the most effective among the various ML models tested. The gradient boost model demonstrated superior performance with an AUROC of 0.826. The SHAP value confirmed that preoperative eGFR, albumin level, and tumor size had a significant impact on the occurrence of CKD after surgery. CONCLUSIONS: We developed a model to predict CKD onset after surgery in patients with RCC. This predictive model is a quantitative approach to evaluate post-surgical CKD risk in patients with RCC, facilitating improved prognosis through personalized postoperative care.