European urology oncology最新文献

Background and objective: While collagen density has been associated with poor outcomes in various cancers, its role in prostate cancer (PCa) remains elusive. Our aim was to analyze collagen-related transcriptomic, proteomic, and urinome alterations in the context of detection of clinically significant PCa (csPCa, International Society of Urological Pathology [ISUP] grade group ≥2).

Methods: Comprehensive analyses for PCa transcriptome (n = 1393), proteome (n = 104), and urinome (n = 923) data sets focused on 55 collagen-related genes. Investigation of the cellular source of collagen-related transcripts via single-cell RNA sequencing was conducted. Statistical evaluations, clustering, and machine learning models were used for data analysis to identify csPCa signatures.

Key findings and limitations: Differential expression of 30 of 55 collagen-related genes and 34 proteins was confirmed in csPCa in comparison to benign prostate tissue or ISUP 1 cancer. A collagen-high cancer cluster exhibited distinct cellular and molecular characteristics, including fibroblast and endothelial cell infiltration, intense extracellular matrix turnover, and enhanced growth factor and inflammatory signaling. Robust collagen-based machine learning models were established to identify csPCa. The models outcompeted prostate-specific antigen (PSA) and age, showing comparable performance to multiparametric magnetic resonance imaging (mpMRI) in predicting csPCa. Of note, the urinome-based collagen model identified four of five csPCa cases among patients with Prostate Imaging-Reporting and Data System (PI-IRADS) 3 lesions, for which the presence of csPCa is considered equivocal. The retrospective character of the study is a limitation.

Conclusions and clinical implications: Collagen-related transcriptome, proteome, and urinome signatures exhibited superior accuracy in detecting csPCa in comparison to PSA and age. The collagen signatures, especially in cases of ambiguous lesions on mpMRI, successfully identified csPCa and could potentially reduce unnecessary biopsies. The urinome-based collagen signature represents a promising liquid biopsy tool that requires prospective evaluation to improve the potential of this collagen-based approach to enhance diagnostic precision in PCa for risk stratification and guiding personalized interventions.

Patient summary: In our study, collagen-related alterations in tissue, and urine were able to predict the presence of clinically significant prostate cancer at primary diagnosis.

Background and objective: Adherence to guideline recommendations can improve the quality of care for patients with prostate cancer (PCa). Our aim was to assess adherence to guidelines for locoregional PCa by international region.

Methods: The study cohort comprised patients diagnosed with locoregional PCa in the 10-country Movember TrueNTH Global Registry (n = 62 688; 2013-2022). We assessed adherence to four quality metrics: (1) active surveillance for low-risk PCa; (2) definitive treatment within 12 mo of diagnosis for unfavorable-risk PCa; (3) no staging imaging for favorable-risk PCa; and (4) staging imaging for unfavorable-risk PCa. For χ² analyses, we combined the three most recent years of data entered by region for each outcome, with adjustment for multiple tests (p = 0.05 ÷ 4 = 0.0125). We also conducted multivariable logistic regression and temporal analyses.

Key findings and limitations: Active surveillance rates for low-risk PCa ranged from 85% in Australia/New Zealand (vs USA: adjusted odds ratio [aOR] 1.042, 95% confidence interval [CI] 0.740-1.520) to 14% in Central Europe (aOR 0.028, 95% CI 0.022-0.036). For patients with unfavorable-risk disease, the highest uptake rate for treatment within 12 mo of diagnosis was in Central Europe (98%; aOR 2.885, 95% CI 1.260-6.603), compared to 70% in Italy (aOR 0.031, 95%CI 0.014-0.072). The proportion of patients with favorable-risk disease who did not undergo imaging ranged from 94% in the USA to 30% in Italy (aOR 0.004, 95% CI 0.002-0.008), while the rate of imaging for unfavorable-risk PCa ranged from 8% in Hong Kong (aOR 65.222, 95% CI 43.676-97.398) to 39% in the USA (all χ²p < 0.0125). Regional temporal trends also varied.

Conclusions and clinical implications: In this international study comparing adherence to quality care metrics for the quality of care for locoregional PCa, we identified regional variance, possibly because of regional differences in cultural attitudes and health care structures. These benchmarks highlight opportunities for interventions to improve adherence to evidence-based guidelines.

Patient summary: Our study shows that adherence to recommended management goals for patients with prostate cancer varies greatly by global region.

Background and objective: Therapeutic options for patients with non-muscle-invasive bladder cancer (NMIBC) have traditionally been limited to intravesical immunotherapy or chemotherapy. A considerable number of new options have been investigated in recent years. Our aim was to review the efficacy and toxicity of novel therapeutic options (results already reported or currently under investigation) for patients with NMIBC.

Methods: We assessed the efficacy of various novel therapeutic options by examining key endpoints in diverse settings, including recurrence, progression, overall survival, disease-specific survival, and complete response. We identified the principal advantages and limitations for each option. Safety was predominantly evaluated as the incidence of grade ≥3 adverse events. Our investigation focused on evidence from scientific articles and congress abstracts published in English within the past 5 yr.

Key findings and limitations: To date, pembrolizumab, nadofaragene firadenovec, and the combination of BCG with N-803 have received US Food and Drug administration approval for the treatment of BCG-unresponsive carcinoma in situ of the bladder (with or without papillary tumours). Five phase 3 trials are recruiting BCG-naïve patients with high-risk NMIBC. There is increasing interest in an ablative rather than an adjuvant approach for patients with intermediate-risk NMIBC.

Conclusions and clinical implications: Novel drugs and device-assisted drug delivery systems are on the verge of changing the treatment of NMIBC. Novel intravesical options seem to have the same efficacy with fewer adverse events in comparison to systemic therapies.

Patient summary: We reviewed new therapy options for non-muscle-invasive bladder cancer. Two agents (pembrolizumab and nadofaragene firadenovec) have been approved to date. Ongoing trials are assessing direct delivery of drugs in solution into the bladder. This route seems to have similar efficacy and fewer side effects than intravenous immunotherapy.

Background and objective: Prostate Imaging for Recurrence Reporting (PI-RR) was introduced in 2021 to standardize the interpretation and reporting of multiparametric magnetic resonance imaging (MRI) for prostate cancer following whole-gland treatment. The system scores image on a scale from 1 to 5 and has shown promising results in single-center studies. The aim of our systematic review and meta-analysis was to assess the diagnostic performance of the PI-RR system in predicting the likelihood of local recurrence after whole-gland treatment.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for diagnostic test accuracy were followed. Relevant databases were searched up to December 2023. Primary studies met the eligibility criteria if they reported MRI diagnostic performance in prostate cancer recurrence using PI-RR. Diagnostic performance for MRI was assessed using two different cutoff points (≥3 or ≥4 for positivity according to the PI-RR system). A meta-analysis with a random-effects model was used to estimate pooled sensitivity and specificity values.

Key findings and limitations: Sixteen articles were identified for full-text reading, of which six were considered eligible, involving a total of 467 patients. Using a cutoff of PI-RR ≥3 (4 studies) for recurrent disease, the sensitivity was 77.8% (95% confidence interval [CI] 69.9-84.1%) and the specificity was 80.2% (95% CI 58.2-92.2%). Using a cutoff of PI-RR ≥4 (4 studies), the sensitivity was 61.9% (95% CI 35.6-82.7%) and the specificity was 86.6% (95% CI 75.1-93.3%). Overall, the inter-rater agreement varied from fair to excellent.

Conclusions and clinical implications: PI-RR is accurate in detecting local recurrence after whole-gland treatment for prostate cancer and shows fair-to-good to excellent inter-reader agreement. Overall, a PI-RR cutoff of ≥3 showed high sensitivity and specificity.

Patient summary: We reviewed studies that reported on how good MRI scans using a scoring system called PI-RR were in detecting recurrence of prostate cancer. We found that this system shows good performance, with fair to excellent agreement between different radiologists.

Background and objective: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.

Methods: We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.

Key findings and limitations: The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to ¹⁷⁷Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).

Conclusions and clinical implications: BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.

Patient summary: We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.

Background and objective: Current management options for localized prostate cancer (PCa) include radical prostatectomy (RP), radiotherapy (RT), and active surveillance (AS). Despite comparable oncological outcomes, there is still lack of evidence on their comparative effectiveness in terms of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). We conducted a systematic review of studies comparing PROMs and PREMs after all recommended management options for localized PCa (RP, RT, AS).

Methods: A literature search was performed in the MEDLINE, EMBASE, and Cochrane CENTRAL databases in accordance with recommendations from the European Association of Urology Guidelines Office and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All prospective clinical trials reporting PROMs and/or PREMs for comparisons of RP versus RT versus AS were included. A narrative synthesis was used to summarize the review findings. No quantitative synthesis was performed because of the heterogeneity and limitations of the studies available.

Key findings and limitations: Our findings reveal that RP mostly affects urinary continence and sexual function, with better results for voiding symptoms in comparison to other treatments. RT was associated with greater impairment of bowel function and voiding symptoms. None of the treatments had a significant impact on mental or physical quality of life. Only a few studies reported PREMs, with a high rate of decision regret for all modalities (up to 23%).

Conclusions and clinical implications: All recommended treatments for localized PCa have an impact on PROMs and PREMs, but for different domains and with differing severity. We found significant heterogeneity in PROM collection, so standardization in real-world practice and clinical trials is warranted. Only a few studies have reported PREMs, highlighting an unmet need that should be explored in future studies.

Patient summary: We reviewed differences in patient reports of their outcomes and experiences after surgical prostate removal, radiotherapy, or active surveillance for prostate cancer. We found differences in the effects on urinary, bowel, and sexual functions among the treatments, but no difference for mental or physical quality of life. Our results can help doctors and prostate cancer patients in shared decision-making.

Background: Hematuria is a cardinal symptom of urinary tract cancer and would require further investigations.

Objective: To determine the ability of renal bladder ultrasound (RBUS) with the Hematuria Cancer Risk Score (HCRS) to inform cystoscopy use in patients with hematuria.

Design, setting, and participants: The development cohort comprised 1984 patients with hematuria from 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) who received RBUS. An independent validation cohort comprised 500 consecutive patients referred to secondary care for a suspicion of bladder cancer.

Outcome measurements and statistical analysis: Sensitivity and true negative of the HCRS and RBUS were assessed.

Results and limitations: A total of 134 (7%) and 36 (8%) patients in the development and validation cohorts, respectively, had a diagnosis of urinary tract cancer. Validation of the HCRS achieves good discrimination with an area under the receiver operating characteristic curve of 0.727 (95% confidence interval 0.648-0.800) in the validation cohort with sensitivity of 95% for the identification of cancer. Utilizing the cutoff of 4.500 derived from the HCRS in combination with RBUS in the development cohort, 680 (34%) patients would have been spared cystoscopy at the cost of missing a G1 Ta bladder cancer and a urinary tract cancer patient, while 117 (25%) patients would have avoided cystoscopy at the cost of missing a single patient of G1 Ta bladder cancer with sensitivity for the identification of cancer of 97% in the validation cohort.

Conclusions: The HCRS with RBUS offers good discriminatory ability in identifying patients who would benefit from cystoscopy, sparing selected patient cohorts from an invasive procedure.

Patient summary: The hematuria cancer risk score with renal bladder ultrasound allows for the triage of patients with hematuria who would benefit from visual examination of the bladder (cystoscopy). This resulted in 25% of patients safely omitting cystoscopy, which is an invasive procedure, and would lead to health care cost savings.

The recurrence rate following endoscopic treatment of non-muscle-invasive bladder cancer (NMIBC) remains high. Standard treatment includes intravesical instillation of chemotoxic agents such as mitomycin C (MMC) to reduce recurrence. It is postulated that upfront administration of hyperthermic intravesical MMC (HIVEC) immediately after transurethral resection of bladder tumour (TURBT) may enhance its efficacy, but evidence from human trials is scant. This pilot study explored the safety of immediate intravesical MMC instillation following TURBT using a conductive HIVEC system (Combat BRS). Patients diagnosed with papillary bladder tumours scheduled for TURBT were recruited. Among 29 patients treated with HIVEC, there was minimal additional postoperative morbidity. The majority (79.3%) were discharged after a hospital stay of 1 d, and no patient required bladder irrigation. There were six grade I-II adverse events (20.7%) and one grade III event (3.4%). No recurrences were observed within 3 mo, and the 12-mo recurrence rate was 4.5%. The study findings demonstrate that immediate HIVEC MMC instillation following TURBT is safe. Further research is needed to assess long-term efficacy in comparison to standard cold MMC. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is treated with tumour removal via a telescope inserted into the bladder through the urethra (called TURBT). We tested the safety of treating the bladder with a warm solution of a chemotherapy drug (mitomycin C) immediately after TURBT, as this may prevent tumour recurrence. The treatment was safe and well tolerated. Further trials are needed with more patients and longer follow-up to confirm the results.

Background and objective: Image-based artificial intelligence (AI) methods have shown high accuracy in prostate cancer (PCa) detection. Their impact on patient outcomes and cost effectiveness in comparison to human pathologists remains unknown. Our aim was to evaluate the effectiveness and cost-effectiveness of AI-assisted pathology for PCa diagnosis in Sweden.

Methods: We modeled quadrennial prostate-specific antigen (PSA) screening for men between the ages of 50 and 74 yr over a lifetime horizon using a health care perspective. Men with PSA ≥3 ng/ml were referred for standard biopsy (SBx), for which cores were either examined via AI followed by a pathologist for AI-labeled positive cores, or a pathologist alone. The AI performance characteristics were estimated using an internal STHLM3 validation data set. Outcome measures included the number of tests, PCa incidence and mortality, overdiagnosis, quality-adjusted life years (QALYs), and the potential reduction in pathologist-evaluated biopsy cores if AI were used. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio.

Key findings and limitations: In comparison to a pathologist alone, the AI-assisted workflow increased the number of PSA tests, SBx procedures, and PCa deaths by ≤0.03%, and slightly reduced PCa incidence and overdiagnosis. AI would reduce the proportion of biopsy cores evaluated by a pathologist by 80%. At a cost of €10 per case, the AI-assisted workflow would cost less and result in <0.001% lower QALYs in comparison to a pathologist alone. The results were sensitive to the AI cost.

Conclusions and clinical implications: According to our model, AI-assisted pathology would significantly decrease the workload of pathologists, would not affect patient quality of life, and would yield cost savings in Sweden when compared to a human pathologist alone.

Patient summary: We compared outcomes for prostate cancer patients and relevant costs for two methods of assessing prostate biopsies in Sweden: (1) artificial intelligence (AI) technology and review of positive biopsies by a human pathologist; and (2) a human pathologist alone for all biopsies. We found that addition of AI would reduce the pathology workload and save money, and would not affect patient outcomes when compared to a human pathologist alone. The results suggest that adding AI to prostate pathology in Sweden would save costs.