Response to RL‐225Ac in prostate cancer: Effect of prior treatment with RL‐177Lu: A systematic review of the literature
Bibliographic record
Abstract
Abstract Background Targeted radionuclide therapy with Actinium‐225‐labeled prostate‐specific membrane antigen agents (225Ac‐PSMA) is currently being studied in clinical trials for patients with metastatic castration‐resistant prostate cancer (mCRPC). Compared to β‐emitting therapeutic radionuclides, alpha‐emitters (e.g., 225Ac) have a significantly higher linear energy transfer and significantly shorter range. As a result, alpha emitters could be expected to improve efficacy and reduce bystander toxicity. This systematic literature review was conducted to evaluate the impact of sequencing of 177Lu‐PSMA and 225Ac‐PSMA targeted radionuclide therapy (TRT) in mCRPC. Methods The present systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines. The searches were made using relevant keywords in the PubMed, Scopus, and Web of Science databases, and articles up to August 22, 2022, were included. Publications were excluded if they were duplicate publications, wrong study or publication format, or discussing a topic out of scope. Data on efficacy, toxicity, and health‐related quality of life were extracted from the individual articles. The I 2 index was used to measure the extent of heterogeneity amongst studies. In the studies that reported subgroup outcomes according to the prior status on 177Lu‐PSMA TRT, pooled estimates of the main outcomes were generated through descriptive analysis. Quality assessment was performed using the Newark−Ottawa‐scale. Results The study included 12 articles; 1 series was performed prospectively. In total, data of 329 patients were analyzed. About 40.1% ( n = 132) of the included men were pretreated with 177Lu‐PSMA TRT. Seven studies, including data of 212 individuals, were eligible for quantitative analysis based on reporting outcomes of the subgroups according to their prior status on 177Lu‐PSMA TRT. >25% PSA decline after 225Ac‐PSMA TRT was lower in individuals who received prior 177Lu‐PSMA TRT (pooled median 42.7%) compared to those who did not (pooled median 15.4%). The pooled medians of the reported median progression‐free survival and overall survival for pretreated versus not pretreated individuals was 4.3 versus 14.3 months and 11.1 versus 9.2 months, respectively. However, the outcomes for each individual study were reported inconsistently ( I 2 = 99.9%). None of the included studies stratified the report of adverse events or changes in health‐related quality of life for the subgroups. Conclusions 225Ac‐PSMA TRT is an experimental treatment for men with mCRPC. There is limited data available from high‐quality trials but so far PSMA‐targeted TRT has demonstrated a low morbidity profile. Our review revealed that there is a possible decrease in efficacy of targeted alpha‐particle therapy if individuals previously were exposed to 177Lu‐PSMA TRT. However, the level of evidence is low. The underlying mechanism by which 177Lu‐PSMA TRT might trigger possible radioresistance as well as randomized controlled trials are required to establish the therapeutic efficacy and safety of 225‐Ac‐PSMA TRT in men refractory to 177Lu‐PSMA TRT.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.001 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".