¹⁷⁷Lu‐PSMA radioligand therapy effectiveness in metastatic castration‐resistant prostate cancer: An updated systematic review and meta‐analysis

Abstract

Background An updated systematic review and meta‐analysis of relevant studies to evaluate the effectiveness of prostate‐specific membrane antigen (PSMA)‐targeted endoradiotherapy/radioligand therapy (PRLT) in castration resistant prostate cancer (CRPC). Methods A systematic search was performed in July 2020 using PubMed/Medline database to update our prior systematic review. The search was limited to papers published from 2019 to June 2020. A total of 472 papers were reviewed. The studied parameters included pooled proportion of patients showing any or ≥50% prostate‐specific antigen (PSA) decline after PRLT. Survival effects of PRLT were assessed based on pooled hazard ratios (HRs) of the overall survival (OS) according to any PSA as well as ≥50% PSA decline after PRLT. Response to therapy based on ≥50% PSA decrease after PRLT versus controls was evaluated using Mantel‐Haenszel random effect meta‐analysis. All p values < 0.05 were considered as statistically significant. Results A total of 45 publications were added to the prior 24 studies. 69 papers with total of 4157 patients were included for meta‐analysis. Meta‐analysis of the two recent randomized controlled trials showed that patients treated with 177Lu‐PSMA 617 had a significantly higher response to therapy compared to controls based on ≥50% PSA decrease. Meta‐analysis of the HRs of OS according to any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. Conclusions PRLT results in higher proportion of patients responding to therapy based on ≥50% PSA decline compared to controls. Any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. Advances in knowledge: This is the first meta‐analysis to aggregate the recent randomized controlled trials of PRLT which shows CRPC patients had a higher response to therapy after PRLT compared to controls.

Radiolabeling and quality control of therapeutic radiopharmaceuticals: optimization, clinical implementation and comparison of radio-TLC/HPLC analysis, demonstrated by [177Lu]Lu-PSMA

“…As more and more academic and general hospitals in Europe are offering radiopharmaceutical therapies like [ 177 Lu]Lu-PSMA therapy (Weineisen et al 2015 ) from an in-house production, the demand for adequate quality control methods is increasing (Kratochwil et al 2019 ; Sadaghiani et al 2022 ; Kalmthout et al 2020 ). Prostate Specific Membrane Antigen (PSMA) labelled with Lu-177 is used for the treatment of metastatic Castration Resistant Prostate Cancer (mCRPC), it’s use has increased after FDA approval of [ 177 Lu]Lu-PSMA-617 (Pluvicto ® ).…”

Evaluation of Tumor Burden Response to Single-cycle of Lu-177 PSMA Treatment with Whole Body Scintigraphic Planar Images in Prostate Cancer Patients

“…Similar to the study of Kind et al (1) a PSA value of >25% was considered as progression in our study. A ≥50% PSA reduction was concidered a biochemical response to treatment in several studies (21,22). A systemic review and meta-analysis of Sadaghiani et al (22) reported a PSA reduction of ≥50% after treatment in 52% of patients.…”

Single Center Experience with a 4-Week 177Lu-PSMA-617 Treatment Interval in Patients with Metastatic Castration-Resistant Prostate Cancer

“…Cumulative knowledge and experience on PSMA-targeted RLT and its efficacy and safety has been accumulating over the last six years [ 1 , 2 ]. PSMA-RLT is becoming recognized as an option for advanced mCRPC patients, but optimal treatment protocols or the safety and efficacy of sequencing and combining PSMA-RLT with other treatments have not yet been established.…”

“…However, there were also high-volume metastatic patients who clearly benefited from serial treatments and experienced a continuous decline of PSA. Both any decline and a ≥50% PSA response in PSMA-RLT have been shown to be linked to better OS in a meta-analysis [ 1 ].…”

“…During the past decade of theranostics research, prostate-specific membrane antigen (PSMA)-targeted internal radiotherapy with 177 lutetium-labeled 177 Lu-PSMA-617 or 177 Lu-PSMA-I&T has been under keen scientific interest due to the limited number of therapeutic options for mCRPC patients [ 1 , 2 ]. Possible candidates for treatment should be evaluated with PET/CT imaging using 68 Ga- or 18 F-labeled PSMA targeting tracers.…”