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: A survival benefit was demonstrated for patients with low-volume synchronous metastatic hormone-sensitive prostate cancer (mHSPCa) when local radiotherapy to the prostate was added to androgen deprivation therapy. This study aims to determine the incidence of prostate cancer-related events and treatments in those who received and those who did not receive external beam radiotherapy for mHSPCa.

Methods: The HORRAD trial is a multicentre randomised controlled trial recruiting originally 432 patients with mHSPCa diagnosed between 2004 and 2014. In a second updated analysis, 328 patients were studied retrospectively for local and nonlocal prostate cancer-related events and treatments. Outcome measurements included the incidence and treatment of local (bladder outlet or ureter obstruction, catheterisation, surgical intervention, ureteric stents, and nephrostomy tubes) and nonlocal (blood transfusions, hospitalisations, and treatment for painful bone metastases) events. Differences between groups were compared using crude and adjusted logistic regression, while time to occurrence of local events was assessed with Kaplan-Meier curves and Cox regression analysis.

Key findings and limitations: A significant difference in the incidence of local events was observed: 30 events in the radiotherapy group versus 50 in the nonradiotherapy group (p = 0.04). Time to occurrence of local interventions was significantly longer in the radiotherapy group (hazard ratio 0.61, 95% confidence interval 0.37-0.99, p = 0.04). The study's limitations include its retrospective nature.

Conclusions and clinical implications: Local radiotherapy to the prostate prolongs local event-free survival significantly and reduces local prostate cancer-related interventions in patients with mHSPCa.