European urology最新文献

Background and objective: Management of metastatic prostate cancer (mPCa) presents significant challenges. In this systematic review, meta-analysis, and meta-regression, the efficacy, safety, and quality of life (QoL) outcomes of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) utilising lutetium-177 ([¹⁷⁷Lu]Lu-PSMA) and actinium-225 ([²²⁵Ac]Ac-PSMA) were assessed.

Methods: A detailed literature search across PubMed/Medline, EMBASE, Web of Science, Scopus, and Cochrane Library was conducted, culminating in the inclusion of 100 studies involving 8711 patients. Data on prostate-specific antigen (PSA) responses, toxicity profiles, and QoL and survival outcomes were analysed. Proportional meta-analyses and meta-regression analyses were performed.

Key findings and limitations: The estimated proportion of patients with PSA decline ≥50% was 0.49 for [¹⁷⁷Lu]Lu-PSMA and 0.60 for [²²⁵Ac]Ac-PSMA in mPCa, particularly metastatic castration-resistant prostate cancer. A meta-regression analysis indicated an association between the cumulative amount of administered activity and the proportion of PSA ≥50% decline. Positive PSA responses were observed alongside improved overall survival across both therapies. Our analyses also identified the key factors associated with PSA responses and survival outcomes, including baseline haemoglobin level, and the presence of visceral metastases. Although anaemia was commonly observed, with [¹⁷⁷Lu]Lu-PSMA, severe toxicities were infrequent. Improved QoL was observed following [¹⁷⁷Lu]Lu-PSMA therapy, whereas it remained stable following the second cycle of [²²⁵Ac]Ac-PSMA treatment. Heterogeneity across studies for PSA responses and toxicity profiles is a limitation.

Conclusions and clinical implications: Our findings suggest an association between PRLT and reductions in PSA levels, as well as associations with enhanced survival outcomes in mPCa. Furthermore, our analysis shows a low incidence of severe toxicity associated with this treatment. These observations highlight the important role of PRLT in the management of mPCa.

Background and objective: The phase 3 MAGNITUDE trial assessed the efficacy and safety of niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in homologous recombination repair (HRR) genes. Here we report final analysis results for patient-reported outcomes (PROs) in the HRR⁺ cohort with a focus on BRCA1/2 alterations (BRCA⁺).

Methods: Protocol-specified endpoints evaluated patient-reported symptoms, health-related quality of life (HRQoL), and tolerability (side-effect bother) using the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EQ-5D-5L questionnaires. Evaluations were completed on day 1 of designated treatment cycles and during follow-up.

Key findings and limitations: All patients with BRCA⁺ mCRPC (n = 225) were included in the PRO analyses with average on-treatment PRO compliance >80% when completed on-site. Time to deterioration in pain according to BPI-SF and FACT-P scores did not significantly differ between niraparib + AAP and placebo + AAP. During treatment, EQ-5D-5L revealed no clinically meaningful differences in overall HRQoL between treatment arms in the BRCA+ subgroup. Finally, tolerability was similar between arms; side effect bother rated as "not at all" or "a little bit" ranged from 79.8% to 95.9% during treatment. Limitations include a sample size that may not have been powered to detect a difference in PROs.

Conclusions and clinical implications: Treatment with niraparib + AAP maintained HRQoL with minimal side-effect bother reported by most patients with BRCA⁺ mCRPC. Differences between treatment groups in time to pain deterioration did not meet conventional levels of statistical significance. The MAGNITUDE trial is registered on ClinicalTrials.gov as NCT03748641.

Background and objective: The Yorkshire Kidney Screening Trial (YKST) assessed the feasibility of adding abdominal noncontrast computed tomography (NCCT) to lung cancer screening to screen for kidney cancer and other abdominal pathology.

Methods: A prospective diagnostic study offered abdominal NCCT to 55-80-yr-old ever-smokers attending a UK randomised lung cancer screening trial (May 2021 to October 2022). The exclusion criteria were dementia, frailty, previous kidney/lung cancer, and computed tomography (CT) of the abdomen and thorax within previous 6 and 12 mo, respectively. Six-month follow-up was undertaken.

Key findings and limitations: A total of 4438 people attended lung screening, of whom 4309 (97%) were eligible for and 4019 (93%) accepted abdominal NCCT. Only 3.9% respondents regretted participating. The additional time to conduct the YKST processes was 13.3 min. Of the participants, 2586 (64%) had a normal abdominal NCCT, whilst 787 (20%) required an abdominal NCCT imaging review but no further action and 611 (15%) required further evaluation (investigations and/or clinic). Of the participants, 211 (5.3%) had a new serious finding, including 25 (0.62%) with a renal mass/complex cyst, of whom ten (0.25%) had histologically proven kidney cancer; ten (0.25%) with other cancers; and 60 (1.5%) with abdominal aortic aneurysms (AAAs). Twenty-five (0.62%) participants had treatment with curative intent. Of the participants, 1017 (25%) had nonserious findings, most commonly benign renal cysts (727 [18%]), whereas only 259 (6.4%) had nonserious findings requiring further tests. The number needed to screen to detect one serious abdominal finding was 18; it was 93 to detect one suspicious renal lesion and 402 to detect one histologically confirmed renal cancer. Limitations of the cohort were fixed age range and being prior lung cancer screening attendees.

Conclusions and clinical implications: In this first prospective risk-stratified screening study of abdominal NCCT offered alongside CT thorax, uptake and participant satisfaction were high. The prevalence of serious findings, cancers, and AAAs, is in the range of established screening programmes such as bowel cancer. Longer-term outcomes and cost effectiveness should now be evaluated.

Background and objective: The PRECISION and PRECISE trials compared magnetic resonance imaging targeted biopsy (MRI ± TB) with the standard transrectal ultrasound (TRUS) guided biopsy for the detection of clinically significant prostate cancer (csPCa). PRECISION demonstrated superiority of MRI ± TB over TRUS guided biopsy, while PRECISE demonstrated noninferiority. The VISION study is a planned individual patient data meta-analysis (IPDMA) comparing MRI ± TB with TRUS guided biopsy for csPCa diagnosis.

Methods: MEDLINE, EMBASE, Web of Science, Cochrane Central of Registered Trials, and ClinicalTrials.gov were searched on the November 12, 2023 for randomised controlled trials of biopsy-naïve patients with a clinical suspicion of prostate cancer undergoing MRI or standard TRUS. Studies were included if its participants with suspicious MRI underwent targeted biopsy alone and those with nonsuspicious lesion avoided biopsy. The primary outcome is the proportion of men diagnosed with csPCa (Gleason ≥3 + 4).

Key findings and limitations: Two studies, PRECISION and PRECISE (953 patients), were included in the IPDMA. In the MRI ± TB arm, 32.2% of patients avoided biopsy due to nonsuspicious MRI. MRI ± TB detected 8.7 percentage points (36.3% vs 27.6%; 95% confidence interval [CI] 2.8-14.6, p = 0.004) more csPCa than TRUS biopsy and 12.3 percentage points (9.6% vs 21.9%; 95% CI 7.8-16.9, p < 0.001) less clinically insignificant prostate cancer (cisPCa; Gleason 3 + 3). The overall risk of bias for the included studies were found to be low after assessment using the QUADAS-2, QUADAS-C, and ROB 2.0 tools.

Conclusions and clinical implications: The MRI ± TB pathway is superior to TRUS biopsy in detecting csPCa and avoiding the diagnosis of cisPCa. MRI should be included in the standard of care pathway for prostate cancer diagnosis.

Background and objective: Image-guided surgical navigation (IGSN) can enhance surgical precision and safety. The expansion of minimally invasive surgery has increased the demand for integration of these navigation systems into robot-assisted surgery. Our objective was to evaluate the integration of electromagnetic tracking with IGSN in robot-assisted sentinel lymph node biopsy (SLNB).

Methods: We conducted a prospective feasibility study to test the use of IGSN in SLNB. In total, 25 patients scheduled for SLNB at The Netherlands Cancer Institute were included (March 2022 to March 2023). SLNB using IGSN was performed using a standardised technique with a da Vinci robot (Intuitive Surgical, Sunnyvale, CA, USA) in four-arm configuration. Feasibility was determined as the percentage of sentinel nodes (SNs) successfully identified via IGSN. Successful SN resection was defined as SNs correctly localised via navigation and validated ex vivo with a gamma probe. Surgeon feedback on the robot-assisted IGSN workflow was evaluated using the System Usability Scale (SUS).

Key findings and limitations: In accordance with the protocol, the first five patients were used for workflow optimisation, and the subsequent 20 patients were included in the analysis. IGSN led to successful identification of 91% (50/55) of the SNs. There were no complications associated with navigation. The surgeon feedback (SUS) was 60.9, with lowest scores reported for the user interface and workflow integration.

Conclusions: IGSN during robot-assisted surgery was feasible and safe. The technique allowed identification and removal of predefined small pelvic lymph nodes.

Patient summary: We carried out a study on the feasibility of imaging-guided navigation in robot-assisted prostate surgery. Our results show that this technique is feasible, safe, and effective.

Background and objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy.

Methods: Patients with advanced UC that progressed or recurred after first-line platinum-based chemotherapy were randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 wk (Q3W) for ≤2 yr or investigator's choice of chemotherapy (paclitaxel [175 mg/m²], docetaxel [75 mg/m²], or vinflunine [320 mg/m²], each Q3W). Endpoints included overall survival (OS) from the initiation of the last treatment prior to death, objective response rate (ORR), and duration of response (DOR) as per Response Evaluation Criteria in Solid Tumors version 1.1 from the date of the first response.

Key findings and limitations: An objective response to pembrolizumab was observed in all groups in terms of a prior response to first-line platinum-based chemotherapy. Median OS, ORR, and median DOR were numerically greater with pembrolizumab than with chemotherapy across subgroups. Patients with PD as the best response to prior platinum-based chemotherapy had the poorest OS outcomes. Limitations include a lack of formal hypothesis testing.

Conclusions and clinical implications: When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC.