Non-Cochrane · intervention · PM41249719
Therapeutic outcomes of ²²⁵Ac/¹⁷⁷Lu-PSMA combination therapy in advanced metastatic Castration-Resistant prostate cancer: A systematic review and Meta-Analysis.
Belabaci Zineddine, Brignoli Giulio, Zilli Thomas, et al. · European journal of nuclear medicine and molecular imaging · 2026 · PubMed · doi:10.1007/s00259-025-07627-y
Findings
20 findings
| Population | ||||
|---|---|---|---|---|
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Thrombocytopenia, grade 3 or higher | Crude pooled proportion 0.06 GRADE not reported 136 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Leukopenia, grade 1 to 2 | Crude pooled proportion 0.30 GRADE not reported 116 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Xerostomia, grade 3 or higher | Crude pooled proportion 0.00 GRADE not reported 265 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | PSA decline of 50% or more (PSA50 response) | Proportion (random-effects, REML) 0.47 [0.37, 0.56] GRADE not reported 8 studies · 323 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Progressive disease by PSA (PSA increase of 25% or more) | Proportion (random-effects, REML) 0.15 [0.07, 0.23] GRADE not reported 8 studies · 323 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Anemia, grade 3 or higher | Crude pooled proportion 0.10 GRADE not reported 136 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Nephrotoxicity, grade 1 to 2 | Crude pooled proportion 0.46 GRADE not reported 116 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Any PSA decline | Proportion (random-effects, REML) 0.78 [0.70, 0.86] GRADE not reported 7 studies · 290 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Leukopenia, grade 3 or higher | Crude pooled proportion 0.02 GRADE not reported 136 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Anemia, grade 1 to 2 | Crude pooled proportion 0.68 GRADE not reported 116 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Xerostomia, grade 1 to 2 | Crude pooled proportion 0.71 GRADE not reported 265 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Stable disease by PSA (PSA increase under 25% or decrease under 50%) | Proportion (random-effects, REML) 0.33 [0.28, 0.39] GRADE not reported 8 studies · 323 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Nephrotoxicity, grade 3 or higher | Crude pooled proportion 0.007 GRADE not reported 136 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | PSA decline of 50% or more (PSA50 response) Six studies in the prior Lu-PSMA exposure subgroup analysis (overall) | Proportion (random-effects, REML) 0.44 [0.32, 0.56] GRADE not reported 6 studies · 169 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Thrombocytopenia, grade 1 to 2 | Crude pooled proportion 0.26 GRADE not reported 116 participants |
| Adults with metastatic castration-resistant prostate cancer (mCRPC) | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Overall survival | Pooled median overall survival (months) 11.8 [9.0, 14.6] GRADE not reported 8 studies |
| Adults with mCRPC previously treated with [177Lu]Lu-PSMA | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | PSA decline of 50% or more (PSA50 response) Prior [177Lu]Lu-PSMA exposure: pre-treated | Proportion (random-effects, REML) 0.41 [0.23, 0.59] GRADE not reported 4 studies · 121 participants |
| Adults with mCRPC previously treated with [177Lu]Lu-PSMA | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Anemia, grade 3 or higher Prior [177Lu]Lu-PSMA exposure: pre-treated | Crude pooled proportion 0.12 GRADE not reported Studies not reported |
| Adults with mCRPC naive to [177Lu]Lu-PSMA | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | Anemia, grade 3 or higher Prior [177Lu]Lu-PSMA exposure: naive | Crude pooled proportion 0.06 GRADE not reported Studies not reported |
| Adults with mCRPC naive to [177Lu]Lu-PSMA | [225Ac]Ac-/[177Lu]Lu-PSMA combination (tandem) radioligand therapy | None (single-arm studies) | PSA decline of 50% or more (PSA50 response) Prior [177Lu]Lu-PSMA exposure: naive | Proportion (random-effects, REML) 0.50 [0.36, 0.64] GRADE not reported 2 studies · 48 participants |
Included primary studies 8
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Khreish 2020 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. PMID:31758224 | 2020 | 1 other review | PSA decline of 50% or more (PSA50 response) | not extracted yet |
| Rathke 2024 Deescalated 225Ac-PSMA-617 Versus 177Lu/225Ac-PSMA-617 Cocktail Therapy: A Single-Center Retrospective Analysis of 233 Patients. PMID:38844358 | 2024 | 1 other review | PSA decline of 50% or more (PSA50 response) | not extracted yet |
| Rosar 2021 (n=15) Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with… PMID:34069003 | 2021 | 1 other review | PSA decline of 50% or more (PSA50 response) | not extracted yet |
| Rosar 2021 (n=17) Molecular imaging and biochemical response assessment after a single cycle of [225Ac]Ac-PSMA-617/[177Lu]Lu-PSMA-617 tandem therapy in… PMID:33754047 | 2021 | 1 other review | PSA decline of 50% or more (PSA50 response) | not extracted yet |
| Rosar 2024 (augmentation, n=33) 225 Ac-PSMA-617 Augmentation in High-Risk mCRPC Undergoing 177 Lu-PSMA-617 Radioligand Therapy : Pilot Experience From a Prospective… PMID:38769643 | 2024 | 1 other review | PSA decline of 50% or more (PSA50 response) | not extracted yet |
| Sheikh 2025 RECIP 1.0 + PSA for response assessment in mCRPC patients treated with 225Ac / 177Lu PSMA combination therapy. PMID:40038098 | 2025 | 1 other review | PSA decline of 50% or more (PSA50 response) | not extracted yet |
| Burgard 2024 Analysis of Molecular Imaging Biomarkers Derived from [18F]FDG PET/CT in mCRPC: Whole-Body Total Lesion Glycolysis (TLG) Predicts Overall… PMID:39456626 | 2024 | this review only | PSA decline of 50% or more (PSA50 response) | not extracted yet |
| Rosar 2025 (REALITY, n=51) 225 Ac-PSMA-617 Augmentation After Insufficient Response Under 177 Lu-PSMA-617 Radioligand Therapy in mCRPC: Evaluation of Outcome and… PMID:39787407 | 2025 | this review only | PSA decline of 50% or more (PSA50 response) | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
| Review | Shared studies | Jaccard |
|---|---|---|
| Beyond [177Lu]Lu-PSMA: a meta-analysis of safety and efficacy of emerging PSMA radioligand therapy agents. (2026) | 6 | 0.17 |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adult men (>18 years) with metastatic castration-resistant prostate cancer | Patients with mCRPC (n=323) |
| Intervention | [225Ac]Ac-/[177Lu]Lu-PSMA combination therapy | Ac-225/Lu-177 PSMA tandem therapy (n=8) |
| Comparison | [225Ac]Ac-PSMA monotherapy, [177Lu]Lu-PSMA monotherapy, or no comparator (single-arm) | None (single-arm studies) |
| Outcomes | PSA responses (any decline, >50% decline, stable disease, progressive disease); overall survival, PSA progression-free survival, adverse events | PSA50 (n=8); any PSA decline (n=7); stable disease (n=8); progressive disease (n=8); median overall survival (n=8); adverse events (n=136) |
| Study designs | Randomized trials, prospective and retrospective studies | Retrospective studies from Germany (n=8) |
| Timing | Not specified | Not specified |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | No | Partial Yes | no |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | NRSI: Partial Yes · RCT: N/A | NRSI: Partial Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | NRSI: Yes · RCT: N/A | NRSI: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Low | no |