BJUI compass最新文献

Background

We present a systematic review and meta-analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor-targeted agent (ARTA) in first- and second-line settings.

Methods

Primary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild-type (HRR−), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second-line setting is also explored. Safety is a secondary end-point.

Results

A total of five phase III (first line: MAGNITUDE, PROpel, TALAPRO-2; second line: PROfound, TRITON3) and two phase II RCTs (second line: NCT01972217, NCT01576172) were selected. In the first-line setting, rPFS was significantly improved in PARPi + ARTA arm in all comers (HR 0.70, p < 0.00001), HRR− (HR 0.76, p = 0.005), HRR+ (HR 0.57, p = 0.0003), and BRCA1/2-mutated patients (HR: 0.33, p < 0.00001). OS was improved in the population with HRR+ status (HR 0.76, p = 0.02) but not statistically significant in BRCA1/2-mutated patients (HR 0.57, 95% CI 0.30–1.08, p = 0.08). In the second line, PARPi improves rPFS (HR for BRCA2 0.31, p = 0.002) and OS (HR for BRCA1/2 0.71, p = 0.01) only in such patients. In this setting, no advantage was reported by adding a PARPi to an ARTA. The arm with PARPi either as monotherapy or in combination with ARTA showed a significantly higher toxicity profile.

Conclusions

PARPi-based therapy represents a compelling treatment option for HRR+ mCRPC, mainly BRCA1/2-mutated patients. However, further biomarker analysis are needed in order to identify other responsive patients across the different disease settings.

Objective

Transrectal (TR) prostate biopsy is being increasingly abandoned in favour of a transperineal (TP) approach as well as a targeted biopsy only of the index lesion(s). It remains underreported how these changes could impact concordance at final pathology. We aimed to evaluate the impact of transitioning from standard transrectal (sTR) to cognitive targeted transperineal (cog-tTP) biopsy on final pathology including concordance and upgrading.

Material and methods

Analysis of consecutive patients undergoing prostate biopsy and prostatectomy (RP) between January 2018 and May 2022 at a tertiary centre in Western Norway.

Results

There were 210 and 239 patients in the sTR and cog-tTP groups, respectively. The mean [IQR] number of biopsies decreased from 12 [4–12] to 3 [3–4] (p < 0.001). The overall rate of concordance between biopsy and final pathology was 64% in both groups (Table 3, Figure 1). 24% Twenty-four per cent (cog-tTP) versus 19% (sTR) had grade group (GG) upgrading, while 12% versus 17% were downgraded (p = 0.2). Regarding positive surgical margins (PSMs) that were >3 mm in extension, there were only 3.3% and 2.1% in the sTR and cog-tTP groups, respectively (p = 0.4). For surgical outcomes associated with RP, no differences in terms of postoperative complications between the groups were found (cog-tTP:10% vs. sTR:6%, p = 0.10).

Conclusion

Transitioning from sTR biopsy to targeted cog-tTP biopsy does not compromise concordance at final pathology nor does it increase the risk of tumour upgrading.

Objectives

To assess the impact of a positive history of venous thromboembolism (VTE) on perioperative outcomes, including length of in-hospital stay, readmission rates, 90-day postoperative complications, and healthcare costs in bladder cancer (BCa) patients undergoing transurethral resection of bladder tumour (TURBT) in the United States.

Patients and Methods

Patients aged ≥18 years with a BCa diagnosis undergoing TURBT were identified in the Merative® Marketscan® Research de-identified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between diagnosis of VTE before TURBT and 90-day complication rates, new postoperative VTE events, re-hospitalization, and total hospital expenditures (2021 US dollars). Sensitivity analyses on VTE severity (pulmonary embolism [PE], deep venous thrombosis [DVT] or superficial thrombophlebitis/phlebitis [SVT]), as well as TURBT extent (minor vs. major) were additionally examined.

Results

In total, 139 800 patients were identified, with 5.3% having preoperative VTE, including DVT (n = 3112, 42.20%), PE (n = 2046, 27.74%) and SVT (n = 2217, 30.06%). A history of preoperative VTE predicted higher rates of any complication (adjusted odds ratio [aOR] 1.28, 95% CI 1.14–1.43) and also higher rates of infectious and haemorrhagic complications. Additionally, preoperative VTE increased the risk of novel VTE events following TURBT (aOR 17.30, 95% CI 16.05–18.65), hospital length of stay (aOR 2.23, 95% CI 1.90–2.62), readmissions (aOR 1.47, 95% CI 1.39–1.56), and hospital associated costs (aOR 1.17, 95% CI 1.12–1.23). DVT and non-minor TURBT procedures did not increase the risk of any, infectious, or haemorrhagic complications, but other associations were maintained regardless of the severity of VTE (PE, DVT, SVT) or TURBT extent (minor/major).

Conclusions

A history of VTE before undergoing transurethral procedures for BCa is associated with significantly worse perioperative outcomes and higher healthcare costs. These findings may help us to counsel on the risks of the intervention and hopefully improve our ability to mitigate such risks.

Objectives

To evaluate the utility of the HAS-BLED bleeding risk-estimation tool to predict for clinically significant postoperative haematuria in patients receiving transurethral resection of prostate (TURP).

Patients and Methods

A single-centre, retrospective cohort analysis of patients underwent TURP from April 2019 to December 2023 for treatment of symptomatic benign prostate hyperplasia. The primary objective was to evaluate reliability of HAS-BLED score in predicting postoperative bleeding event. A focus sub-analysis was performed on anticoagulated patient cohort. Each patient was categorised in to HASBLED low-, moderate- and high-risk group according to the preestablished estimator tool. Patients' demographics, clinical, pathological and operative details were collected. Events of clinically significant haematuria within 3 months postoperatively were captured. Cohort characteristics and outcome were analysed with two-sided t test and ANOVA test. Further weight-adjusted multivariable analysis and ROC curve was performed to evaluate the predictive value of HAS-BLED score.

Results

Our analysis showed that patients assigned as high-risk by HAS-BLED were at 2.17-times higher chance of developing clinically significant haematuria compared to the low-risk patients. The risk for high-risk patient was 18.5% (95%CI 11.7–25.3%) and 8.5% (95%CI 4.6–12.4%) for low-risk patients. Moderate-risk did not demonstrate any significant difference relative to the low-risk group. Sub-analysis of 113 patients receiving long-term anticoagulation accentuates the utility of the tool. The risk of haematuria for high-risk patient was 32.7% (95%CI 20.7–44.7%), moderate-risk patient was 28.7% (95%CI 17.0–40.3%), and low-risk patient was 9.7% (95%CI 4.2–15.2%). In this cohort, the risk of haematuria was 3.37 and 2.96 times higher in the high and moderate-risk compared to the low-risk group, respectively.

Conclusion

This is the first study to validate a bleeding estimator tool for TURP patients. High HAS-BLED score positively predicts clinically significant post-TURP haematuria, particularly for patients receiving anticoagulation therapy.

Objective

To evaluate the correlation between ATP-binding cassette (ABC) transporter expression and therapeutic efficacy of enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, in urothelial cancer, as only a few studies have been conducted on this topic.

Patients and methods

This retrospective study included 20 patients with metastatic urothelial carcinoma (mUC), including bladder and upper urinary tract cancers, who were treated with EV at Dokkyo Medical University Hospital between 2022 and 2024. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue samples. Progression-free survival (PFS) was estimated using the Kaplan–Meier method, and differences between subgroups (e.g., Nectin-4 and ABC transporter expression) were compared using the log-rank test.

Results

Immunohistochemical analysis indicated that tumours with high ABC transporter expression exhibited shorter PFS time and poorer response to EV. Furthermore, a decrease in Nectin-4 expression and an increase in ABC transporter expression were observed as the disease progressed from non-muscle-invasive to muscle-invasive and metastatic. Patients with Nectin-4-positive and ABC transporter-negative tumours had the longest PFS, underscoring the prognostic significance of these biomarkers.

Conclusion

To our knowledge, this study is the first to show a correlation between ABC transporter expression and EV efficacy in urothelial carcinoma. Future research should focus on optimizing treatment strategies based on Nectin-4 and ABC transporter expression to improve outcomes.

Background

Despite guideline recommendations, few institutions have implemented clinical pathways that incorporate frailty into routine decision-making for patients undergoing radical cystectomy (RC). This paper presents an integrated clinical pathway designed to address the needs of frail patients undergoing RC. The purpose of the study is to determine whether a multifaceted prevention programme that tailors interventions to the syndromic components of frailty can improve postoperative morbidity and recovery time for patients. New insights will be gained into how to optimize the physical and mental status and quality of life of patients before and after surgery, up to 1 year later.

Study design

The Global RAdical Cystectomy Evaluation and Management (GRACEM) study is a prospective, observational, single-centre, 2-year cohort study. Patient enrolment began on 27 April 2023, and results are pending.

Endpoints

The primary endpoints are postoperative morbidity and the in-hospital postoperative care burden. Postoperative morbidity is measured by the number of early (up to 1 month) and late (over 1 month and up to 12 months) complications, graded by severity according to the Clavien–Dindo classification. In-hospital postoperative care burden is measured by the number and duration of key care processes as recorded by the Care Process Monitoring Chart, a tool developed for this study. Secondary endpoints are changes in frailty and health-related quality of life (HRQoL) from pre-intervention to planned follow-up up to 1 year. Frailty is assessed with the Functional Limitations and Geriatric Syndromes Frailty Questionnaire (FLIGS-FQ), another ad hoc tool. HRQoL is assessed using the EQ-5D-5L questionnaire combined with the cystectomy-specific FACT-Bl-cys index from the first month of follow-up.

Patients and methods

The GRACEM study includes patients with non-metastatic, histologically confirmed, muscle-infiltrating bladder cancer who underwent RC surgery with curative intent. This study is unique in that the GRACEM Core Team shares decision-making throughout the pathway, from before the intervention to the end of the patient's follow-up. The pathway involves the patient, family members and community services.

Objectives

To assess the contemporary malignancy rate in isolated de novo red patches in the bladder and associated risk factors for better selection of red patch biopsy.

Patients

Patients from the IDENTIFY dataset; Patients referred to secondary care with suspected urinary tract cancer and found to have isolated de novo red patches on cystoscopy.

Methods

We reported the unadjusted cancer prevalence in isolated de novo red patches that were biopsied; multivariable logistic regression was used to explore cancer-associated risk factors including age, sex, smoking, type of haematuria, LUTS, UTIs and a suspicious-looking red patch (as reported by the cystoscopist). Sub-analysis of these by clinical role and experience was performed.

Results

A total of 1110 patients with isolated de novo red patches were included. 41.5% (n = 461) were biopsied, with a malignancy rate of 12.8% (59/461), which was significantly higher in suspicious versus non-suspicious red patches (19.1% vs. 2.81%, p < 0.01). There was a significant association between bladder cancer and age (OR 1.04, 95% CI 1.01–1.07, p = 0.01), smoking history (OR 2.62, 95% CI 1.09–6.27, p = 0.03) and suspicious-looking patch (OR 6.50, 95% CI 2.47–17.1, p < 0.01). The majority of malignancies were in over 60-year-olds. Malignancy rates in suspicious versus non-suspicious red patches did not differ significantly between clinical roles or experiences.

Limitations included subjectivity in classifying a suspicious patch and selection bias as not all patches were biopsied.

Conclusions

Many patients still undergo unnecessary biopsies under general anaesthetic for isolated de novo red patches. Clinicians should consider the patient's age, smoking status and how suspicious-looking the patch is, before deciding on surveillance versus biopsy to improve cancer diagnostic yield.

Objectives

To evaluate the feasibility and safety of robotic-assisted salvage radical cystectomy (RA-SRC).

Materials and Methods

We retrospectively searched the prospectively collected surgical database of two highly experienced robotic urological surgeons for cases of RA-SRC, defined as RARC performed post-previous pelvic RT for palliative or oncologic treatment purposes. Collected data included demographic and clinical information and outcome measures including operative course, hospital stay and complications.

Results

Eighteen patients were included in the current analysis. All patients had previous RT to the pelvis with 12 patients also having prior radical pelvic surgery. Indications for salvage cystectomy were either palliation (n = 12) or oncological (MIBC or high risk NMIBC, n = 6). There were no intraoperative complications and no conversions to open surgery. Ninety day postoperative complications were recorded in 11 patients (61.1%), with major complications (Clavien–Dindo grades 3 and 4) in three patients (16.6%). After a median follow-up of 43.5 months, one late postoperative complication was observed requiring surgical intervention.

Conclusion

Our data, together with the limited published data from other cohorts of RA-SRC, suggest that in experienced hands, RA-SRC is feasible, with intraoperative and perioperative complication rates that are lower than the published data for open SRC and are equivalent to open primary RC. These data will contribute to treatment decision making both in patients with post-pelvic radiation symptoms requiring palliation and patients with MIBC considering or treated with trimodal treatment.

Objectives

To analyse and compare the functionality of extraluminal and intraluminal artificial urinary sphincters (AUSs), an in silico procedure has been defined and applied. Design and reliability assessments of the AUS are typically performed using a clinical approach, which does not provide data on mechanical stimulation of urethral tissues. Mechanical stimulation may determine tissue degeneration, such as urethral atrophy or erosion, the main causes of AUS failure. In silico techniques can provide a quantitative description of stress and strain fields due to the interaction between tissues and AUS and allow investigating an extremely large number of situations, considering different configurations of AUS and urethra.

Materials and Methods

Computational investigations were carried out to evaluate the mechanical reliability of the main extraluminal and intraluminal AUS, AMS 800 and Relief. The lower urinary tract was modelled based on previous experiments. The AUS models took into account the main components that interact with biological tissues. Urethra and AUS models were coupled and used to investigate mechanical stimulation of urethral tissues.

Results

In silico simulations provide quantitative information about the mechanical stimulation of urethral tissue, such as compressive strain and stress and hydrostatic pressure, due to interaction with the AUS. Such mechanical quantities allow a comparison of reliability between extraluminal and intraluminal devices.

Conclusions

The activities define and demonstrate the effectiveness of a novel in silico approach to the design and reliability assessment of AUS devices, increasing the investigative possibilities and reducing the time, ethical and economic costs.