World Journal of Urology最新文献

Purpose: Surgery remains the cornerstone of localized renal cell carcinoma (RCC) care. Pembrolizumab has recently been recommended as a standard of care for RCC patients who are at high risk of recurrence. Data regarding the efficacy of ICIs either alone or in combination with ICIs or VEGF TKIs for VTT shrinkage are scarce.

Methods: In the framework of the French kidney cancer research network UroCCR (NCT03293563), we performed a retrospective multicentric European study to evaluate VTT shrinkage in patients treated with ICIs with metastatic or locally advanced renal cell carcinoma (RCC). The primary endpoint was the objective response rate (ORR) of patients with VTT to ICI-based therapy. Radiological assessment was performed by a treating physician according to the RECISTv1.1 criteria.

Results: We included 44 patients. The median age was 69 years (range 37-88). All patients was intermediate or poor IMDC risk group. Twenty-three patients were treated with anti-PD-1 in combination with anti-CTLA-4 therapy, 13 patients with ICI monotherapy, and 8 patients with ICIs in combination with antiangiogenic TKI. At baseline, the median VTT diameter was 22 mm (range 7-93). After a median duration of treatment of 5.8 months (range 1.8-39.1), the ORR was 38% (n = 17), including 4 complete responses (CRs) and 13 partial responses (PRs). Ten patients had stable disease (SD), and 17 had progressive disease (PD) as the best response of the VTT.

Conclusion: These data highlight the potential efficacy of ICIs to shrink the VTT even if they seem to have little impact on the extent of VTT.

Purpose: To develop a deep learning (DL) model based on primary tumor tissue to predict the lymph node metastasis (LNM) status of muscle invasive bladder cancer (MIBC), while validating the prognostic value of the predicted aiN score in MIBC patients.

Methods: A total of 323 patients from The Cancer Genome Atlas (TCGA) were used as the training and internal validation set, with image features extracted using a visual encoder called UNI. We investigated the ability to predict LNM status while assessing the prognostic value of aiN score. External validation was conducted on 139 patients from Renmin Hospital of Wuhan University (RHWU; Wuhan, China).

Results: The DL model achieved area under the receiver operating characteristic curves of 0.79 (95% confidence interval [CI], 0.69-0.88) in the internal validation set for predicting LNM status, and 0.72 (95% CI, 0.68-0.75) in the external validation set. In multivariable Cox analysis, the model-predicted aiN score emerged as an independent predictor of survival for MIBC patients, with a hazard ratio of 1.608 (95% CI, 1.128-2.291; p = 0.008) in the TCGA cohort and 2.746 (95% CI, 1.486-5.076; p < 0.001) in the RHWU cohort. Additionally, the aiN score maintained prognostic value across different subgroups.

Conclusion: In this study, DL-based image analysis showed promising results by directly extracting relevant prognostic information from H&E-stained histology to predict the LNM status of MIBC patients. It might be used for personalized management of MIBC patients following prospective validation in the future.

Purpose: The purpose of this study was to investigate the efficacy of Transurethral Holmium Laser of the Prostate (HoLEP) with Double-n Technology in the treatment of benign prostatic hyperplasia (BPH), with a focus on preserving sexual function postoperatively.

Methods: Conducted as a multicenter, prospective, single-blind randomized controlled trial, this study enrolled sexually active male patients with BPH. Participants were randomized into three groups: standard HoLEP (Group A), single-n technology (Group B), and innovative double-n technology (Group C), which emphasizes the preservation of the urethral mucosa and nearby structures. The primary endpoints included maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF).

Results: Of the 180 initial participants, 139 completed the study. All groups showed significant improvements in Qmax and IPSS. Initial declines in IIEF scores were noted across all groups, stabilizing to baseline by 3 months without further improvement. Group A had modest antegrade ejaculation rates, starting at 15.4% at 3 months and reaching 23.1% at 12 months. Group B showed a significant improvement, with AE rates rising from 31.8% at 3 months to 45.5% at 12 months, significantly higher than Group A (p < 0.05). Group C had the highest AE rates, starting at 57.8% at 3 months and reaching 77.8% at 12 months, significantly surpassing both Group A and B (p < 0.05). Regarding semen reduction, Group A had 100% reduction at 3 months, which decreased to 77.8% at 12 months. Group B followed a similar trend, from 100% at 3 months to 68.2% at 12 months. Group C showed a more pronounced decline, starting at 84.6% at 3 months and dropping to 37.1% at 12 months, with values significantly lower than both Groups A and B (p < 0.05).

Conclusions: The double-n HoLEP technique shows promising results in improving urinary symptoms while better preserving ejaculatory function and sexual quality of life in BPH patients. This technique could offer a significant advancement in the surgical management of BPH, particularly for sexually active patients.

Purpose: Preoperative C-reactive protein (CRP) is a valuable prognostic biomarker in nonmetastatic clear cell renal cell carcinoma (nmccRCC). Incorporation of CRP into prognostic models may improve the prediction of oncologic outcomes. Herein, we aimed to develop and validate prognostic nomograms and an integrated software incorporating preoperative CRP level in nmccRCC.

Methods: An international multi-institutional database was retrospectively analyzed for nmccRCC patients undergoing surgery. A total of 2284 patients were enrolled and randomly allocated to training (n = 1599, 70%) and validation (n= 685, 30%) cohorts. Nomograms predicting overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were developed in the training cohort using multivariable Cox regression, including preoperative CRP levels and other clinical factors. An integrated software was also created. The validation cohort was used to assess the performance of these nomograms.

Results: Following a median follow-up of 5.9 years, 318 (13.92%) patients died of any cause, 109 (4.77%) died of renal cancer, and 282 (12.35%) developed recurrence. The median (interquartile range) preoperative CRP level was 1.90 (0.80-5.68) mg/L. A high CRP level was independently associated with worse OS, CSS, and RFS. The nomograms and integrated software incorporating CRP significantly improved prediction accuracy compared with CRP alone. The C-indices for nomograms were 0.74 (95%CI, 0.69-0.80) for OS, 0.87 (0.82-0.93) for CSS, and 0.77 (0.71-0.82) for RFS in the validation cohort. Acceptable calibration was demonstrated at 12/36/60 months for OS, CSS, and RFS.

Conclusions: The prognostic nomograms and the user-friendly integrated software incorporating preoperative CRP level may facilitate individualized risk stratification and treatment planning for patients with nmccRCC.

Background and objectives: Radical prostatectomy is a standard treatment for prostate cancer, yet about 30% of patients experience rising biochemical markers within a decade post-surgery. Pelvic lymph node sampling during prostatectomy assesses potential lymph node metastases, but standard histological assessments, which typically examine only 2-3 tissue sections, often miss occult metastases. This study assesses the effectiveness of qPCR in detecting PSA coding KLK3 mRNA for identifying lymph node metastases post-prostatectomy and explores the correlation between PSA-mRNA and biochemical recurrence.

Methods: A cohort of 157 patients who underwent radical prostatectomy with lymphadenectomy were examine. On average, 24.7 lymph nodes were removed per patient. Among them, 108 patients reached PSA value below 0.1 ng/ml without receiving additional therapy, and 106 were followed up over a duration of 5.4 years. This subgroup is of particular interest because it allows for the investigation of the correlation between the occurrence of PSA-mRNA in lymph nodes and later biochemical recurrence. Key findings and limitations qPCR of PSA-mRNA identified 47 out of 108 positive cases (43.5%), while histopathological examination only detected 16 out of 108 cases (14.8%). From the followed-up subgroup 37 out of 106 patients (34.9%) experienced biochemical recurrence. It is noteworthy that qPCR yields more positive findings, regardless of the presence of biochemical recurrence.

Conclusion and clinical implications: The study findings illustrate that qPCR consistently outperforms conventional histology in detecting lymph node metastases, regardless of biochemical recurrence. The hypothesis that qPCR is better at predicting later biochemical recurrence than conventional histology has not been confirmed.

Purpose: To evaluate the association between the newly developed region of interest (ROI)-modified Mayo Adhesive Probability (MAP) score, in which stranding was re-evaluated by computed tomography (CT) number, for predicting operation time in robot-assisted partial nephrectomy (RAPN).

Methods: The study participants were 119 patients who underwent transperitoneal RAPN. With regard to stranding, ROIs were evaluated, and the mean CT numbers were assigned a score ranging from 0 to 3. Clinical variables were evaluated in a multivariate logistic regression analysis in relation to prolonged operation time.

Results: The percentage of patients with score ≥ 3 by MAP score alone was significantly higher than those of patients with score ≥ 3 by ROI-modified MAP score alone (26.8% vs. 13.4%, p < 0.001). Multivariate analysis revealed no independent association with the MAP score. On the other hand, for ROI-modified MAP score, score ≥ 3 was an independent factor for prolonged operation time (OR = 4.28, p = 0.0032) along with body mass index (BMI) ≥ 22 (OR = 4.46, p = 0.01), R.E.N.A.L. nephrometry score ≥ 7 (OR = 4.12, p = 0.0047), posterior tumor location (OR = 2.85, p = 0.036), and clinical T stage ≥ 1b (OR = 6.19, p = 0.0044). Regarding the predictive performance, the accuracy of the ROI-modified MAP score was significantly higher than the MAP score (area under the curve [AUC] value: 0.652 vs. 0.721, p = 0.034).

Conclusion: The ROI-modified MAP score was a more relevant factor regarding operation time, suggesting that it might be a better preoperative predictor.

Purpose: This study aims to elucidate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in Hunner-type Interstitial Cystitis (HIC) and evaluate its potential as a therapeutic target.

Methods: Bladder tissue samples were obtained from HIC patients and normal bladder tissue from bladder cancer patients. PACAP expression was assessed through immunohistochemistry. An in vitro HIC model was established using LPS-induced SV-HUC1 cells. PACAP knockdown was performed using siRNA. The expression of inflammatory markers (IL-6, IL-1β, TNF-α) and fibrotic markers (fibronectin 1, TGF-β1, collagen I) was evaluated via qPCR, Western blot, and ELISA. Cell migration and proliferation were analyzed using wound healing and CCK-8 assays. Transcriptomic profiling was conducted to identify differentially expressed genes (DEGs) and explore their functional significance.

Results: PACAP expression was significantly elevated in the bladder tissues of HIC patients. LPS stimulation of SV-HUC1 cells induced PACAP expression alongside increased levels of inflammatory cytokines, validating the inflammatory model. PACAP knockdown markedly suppressed IL-6, IL-1β, and TNF-α expression and attenuated LPS-induced fibrosis by reducing fibronectin 1, TGF-β1, and collagen I levels. Additionally, PACAP knockdown inhibited LPS-induced cell migration and proliferation, as evidenced by wound healing and CCK-8 assays. Transcriptomic analysis revealed distinct molecular alterations in HIC tissues, including PACAP upregulation, implicating it in HIC pathogenesis.

Conclusion: PACAP plays a pivotal role in the inflammatory and fibrotic pathways of HIC. PACAP knockdown alleviates LPS-induced pathological responses, highlighting its potential as a novel therapeutic target. Further research is warranted to investigate PACAP's precise mechanisms in HIC and its translational application in clinical settings.

Purpose: Up to 50% of high-risk non-muscle invasive bladder cancer (HR-NMIBC) patients fail Bacillus Calmette-Guérin (BCG) treatment, resulting in a high risk of progression and poor clinical outcomes. Biomarkers that predict outcomes after BCG are lacking. The antitumor effects of BCG are driven by a cytotoxic T cell response, which may be controlled by immune checkpoint proteins like Programmed Death Ligand 1 (PD-L1). Here, we hypothesized that PD-L1 protein expression could serve as a biomarker for BCG-failure.

Methods: HR-NMIBC patients who received ≥ 5 BCG instillations were included. Tissue microarrays were constructed from BCG-naïve tumors and recurrences and stained with the PD-L1 (SP142) antibody. PD-L1 status was defined as ≥ 5% tumor-infiltrating immune cells with membrane staining in the tumor area. Clinicopathological associations with PD-L1 positive tumors were investigated, and time-to-event analyses were performed comparing PD-L1 positive vs. negative tumors.

Results: 432 BCG-naïve tumors and 160 recurrences were included, and 91% of patients received adequate BCG. In BCG-naïve tumors, PD-L1 was expressed in 7% of patients and PD-L1 expression was associated with stage T1 versus Ta disease (p = 0.015). PD-L1 expression was not associated with treatment failure after adequate BCG (p = 0.782) nor with progression-free survival (p = 0.732). Testing cut-offs of ≥ 1% and ≥ 10% PD-L1 positivity did not alter results. High PD-L1 expression was more frequent in tumor recurrences (14%) as compared to BCG-naïve tumors (p = 0.012).

Conclusion: PD-L1 expression in HR-NMIBC is not a biomarker of response to BCG. However, PD-L1 is higher in a subset of tumors that failed BCG treatment. More research is needed to determine the role of PD-L1 in tumors where BCG treatment failed.