Lutetium [Lu-177] chloride 1GBq/0.025ml radiopharmaceutical precursor solution vials

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.

Abstract licence: CC BY

Lutetium-177 (Lu-177)-labelled radioligand therapies (RLT) targeting prostate-specific membrane antigen (PSMA) present a promising treatment for patients with progressive metastasized castration-resistant prostate cancer (mCRPC). Personalized dosimetry, facilitated by post-therapeutic imaging, offers the potential to enhance treatment efficacy by customizing radiation doses to individual patient needs, thereby maximizing therapeutic benefits while minimizing toxicity to healthy tissues. However, implementing personalized dosimetry is resource-intensive, requiring multiple single-photon emission-computed tomography (SPECT)/CT scans and posing significant logistical challenges for both healthcare facilities and patients. Despite these challenges, personalized dosimetry can lead to optimized radiation delivery, improved safety, and better management of complex cases. Nevertheless, the financial and resource burdens complicate its adoption in routine clinical practice. While the European Association of Nuclear Medicine (EANM) supports personalized dosimetry, standardization is lacking due to these practical constraints. Further research and streamlined methodologies are essential to balance the benefits and feasibility of personalized dosimetry, potentially improving treatment outcomes for mCRPC patients.

Abstract licence: CC BY