Non-Cochrane · intervention · PM41872814
Beyond [177Lu]Lu-PSMA: a meta-analysis of safety and efficacy of emerging PSMA radioligand therapy agents.
Abdlkadir Ahmed Saad, Al-Adhami Dhuha, Moghrabi Serin, et al. · BMC cancer · 2026 · PubMed · doi:10.1186/s12885-026-15900-y
Findings
Population Patients with metastatic castration-resistant prostate cancer (mCRPC)
93 findings
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 86 [82, 90] GRADE not reported 31 studies · 1406 participants |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Xerostomia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 68 [55, 81] GRADE not reported 28 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Anemia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 41 [27, 55] GRADE not reported 21 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · TRT emission: beta/Auger emitters | Pooled proportion (%) 75 [60, 91] GRADE not reported 8 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Fatigue grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 55 [29, 80] GRADE not reported 8 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Baseline PSA: 100 ng/ml or higher | Pooled proportion (%) 87 [82, 91] GRADE not reported 25 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Thrombocytopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 21 [12, 30] GRADE not reported 18 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Leukopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 21 [14, 30] GRADE not reported 20 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Nephrotoxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 20 [8, 35] GRADE not reported 12 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Xerostomia grade 3 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 11 [4, 22] GRADE not reported 7 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Age group: Geriatrics | Pooled proportion (%) 82 [73, 89] GRADE not reported 17 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Sample size: 30 or more participants | Pooled proportion (%) 90 [86, 94] GRADE not reported 10 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Sample size: <30 participants | Pooled proportion (%) 80 [73, 87] GRADE not reported 21 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Baseline PSA: 100 ng/ml or higher | Pooled proportion (%) 56 [50, 63] GRADE not reported 25 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Nephrotoxicity grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 4 [2, 7] GRADE not reported 9 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Age group: Middle age | Pooled proportion (%) 90 [85, 94] GRADE not reported 14 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Age group: Middle age | Pooled proportion (%) 66 [57, 73] GRADE not reported 14 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Study design: Prospective studies | Pooled proportion (%) 81 [67, 92] GRADE not reported 8 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Heavy pretreatment: 3 or more therapy lines | Pooled proportion (%) 56 [49, 63] GRADE not reported 26 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Thrombocytopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 7 [4, 10] GRADE not reported 14 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Hepatotoxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 19 [6, 38] GRADE not reported 4 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Age group: Geriatrics | Pooled proportion (%) 57 [50, 63] GRADE not reported 17 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Sample size: <30 participants | Pooled proportion (%) 47 [37, 56] GRADE not reported 21 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Gastrointestinal toxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 31 [19, 45] GRADE not reported 8 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Fatigue grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 3 [1, 10] GRADE not reported 2 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · TRT emission: beta/Auger emitters | Pooled proportion (%) 46 [26, 66] GRADE not reported 8 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Heavy pretreatment: 3 or more therapy lines | Pooled proportion (%) 83 [82, 90] GRADE not reported 26 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Leukopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 3 [2, 6] GRADE not reported 10 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Overall adverse event rate (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 26 [22, 31] GRADE not reported 32 studies · 1390 participants |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · TRT emission: alpha/beta emitters | Pooled proportion (%) 51 [41, 63] GRADE not reported 7 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · TRT emission: alpha emitters | Pooled proportion (%) 62 [54, 70] GRADE not reported 17 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Study design: Prospective studies | Pooled proportion (%) 41 [27, 57] GRADE not reported 8 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Study design: Retrospective studies | Pooled proportion (%) 87 [83, 91] GRADE not reported 23 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Study design: Retrospective studies | Pooled proportion (%) 61 [55, 68] GRADE not reported 23 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Bone pain flare (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 10 [2, 21] GRADE not reported 4 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · TRT emission: alpha emitters | Pooled proportion (%) 88 [84, 92] GRADE not reported 17 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 57 [50, 63] GRADE not reported 31 studies · 1406 participants |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Sample size: 30 or more participants | Pooled proportion (%) 69 [61, 75] GRADE not reported 10 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · TRT emission: alpha/beta emitters | Pooled proportion (%) 84 [70, 94] GRADE not reported 7 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Heavy pretreatment: fewer than 3 therapy lines | Pooled proportion (%) 86 [82, 90] GRADE not reported 5 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) · Baseline PSA: below 100 ng/ml | Pooled proportion (%) 81 [66, 93] GRADE not reported 6 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Anemia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 10 [7, 14] GRADE not reported 18 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Baseline PSA: below 100 ng/ml | Pooled proportion (%) 56 [35, 76] GRADE not reported 6 studies |
| PSMA radioligand therapy agents beyond [177Lu]Lu-PSMA ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) · Heavy pretreatment: fewer than 3 therapy lines | Pooled proportion (%) 60 [41, 80] GRADE not reported 5 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 62 [54, 70] GRADE not reported 17 studies · 1015 participants |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Overall adverse event rate (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 28 [21, 34] GRADE not reported 18 studies · 1025 participants |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Leukopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 18 [9, 29] GRADE not reported 12 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Gastrointestinal toxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 44 [32, 56] GRADE not reported 4 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 88 [84, 92] GRADE not reported 17 studies · 1015 participants |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Thrombocytopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 17 [6, 32] GRADE not reported 11 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Thrombocytopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 5 [2, 9] GRADE not reported 7 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Nephrotoxicity grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 3 [2, 5] GRADE not reported 7 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Xerostomia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 82 [70, 92] GRADE not reported 18 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Xerostomia grade 3 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 12 [3, 24] GRADE not reported 6 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Nephrotoxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 24 [7, 48] GRADE not reported 5 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Fatigue grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 68 [49, 84] GRADE not reported 3 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Hepatotoxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 13 [6, 22] GRADE not reported 3 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Anemia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 40 [21, 60] GRADE not reported 13 studies |
| [225Ac]Ac-PSMA monotherapy | None (single-arm studies) | Anemia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 9 [4, 15] GRADE not reported 10 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Anemia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 10 [5, 17] GRADE not reported 5 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Overall adverse event rate (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 20 [10, 33] GRADE not reported 7 studies · 326 participants |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Thrombocytopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 23 [15, 31] GRADE not reported 2 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Leukopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 22 [14, 30] GRADE not reported 2 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Nephrotoxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 11 [5, 19] GRADE not reported 3 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 51 [41, 62] GRADE not reported 7 studies · 262 participants |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Anemia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 35 [8, 68] GRADE not reported 3 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Thrombocytopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 6 [2, 11] GRADE not reported 3 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 84 [70, 94] GRADE not reported 7 studies · 262 participants |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Xerostomia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 42 [5, 84] GRADE not reported 7 studies |
| [177Lu]Lu/[225Ac]Ac-PSMA tandem therapy | None (single-arm studies) | Leukopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 3 [1, 7] GRADE not reported 2 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Thrombocytopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 11 [1, 29] GRADE not reported 2 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Thrombocytopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 25 [13, 38] GRADE not reported 2 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Anemia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 16 [3, 35] GRADE not reported 2 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Leukopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 31 [18, 45] GRADE not reported 3 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Anemia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 56 [27, 82] GRADE not reported 3 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Fatigue grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 55 [10, 99] GRADE not reported 3 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 81 [69, 92] GRADE not reported 5 studies · 65 participants |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Nephrotoxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 25 [1, 69] GRADE not reported 4 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Overall adverse event rate (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 24 [14, 33] GRADE not reported 5 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Bone pain flare (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 10 [1, 23] GRADE not reported 3 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 46 [25, 68] GRADE not reported 5 studies · 65 participants |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Gastrointestinal toxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 10 [3, 21] GRADE not reported 2 studies |
| [161Tb]Tb-PSMA therapy | None (single-arm studies) | Xerostomia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 54 [33, 75] GRADE not reported 2 studies |
| [131I]PSMA therapy | None (single-arm studies) | Thrombocytopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 29 [17, 43] GRADE not reported 3 studies |
| [131I]PSMA therapy | None (single-arm studies) | Objective response rate (ORR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 48 [13, 84] GRADE not reported 3 studies · 54 participants |
| [131I]PSMA therapy | None (single-arm studies) | Xerostomia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 51 [6, 95] GRADE not reported 3 studies |
| [131I]PSMA therapy | None (single-arm studies) | Fatigue grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 13 [4, 26] GRADE not reported 2 studies |
| [131I]PSMA therapy | None (single-arm studies) | Leukopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 6 [0, 16] GRADE not reported 2 studies |
| [131I]PSMA therapy | None (single-arm studies) | Gastrointestinal toxicity grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 24 [7, 46] GRADE not reported 2 studies |
| [131I]PSMA therapy | None (single-arm studies) | Leukopenia grade 1-2 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 32 [1, 84] GRADE not reported 3 studies |
| [131I]PSMA therapy | None (single-arm studies) | Thrombocytopenia grade 3-4 (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 19 [8, 32] GRADE not reported 2 studies |
| [131I]PSMA therapy | None (single-arm studies) | Overall adverse event rate (pooled incidence) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 25 [14, 38] GRADE not reported 3 studies · 54 participants |
| [131I]PSMA therapy | None (single-arm studies) | Disease control rate (DCR) Nuclear medicine centers (mostly single-center) | Pooled proportion (%) 75 [35, 99] GRADE not reported 3 studies · 54 participants |
Included primary studies 34
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Khreish 2019 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. PMID:31758224 | 2020 | 1 other review | not stated | 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 | not stated | not extracted yet |
| Rosar 2021a 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 | not stated | not extracted yet |
| Rosar 2021b 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 | not stated | not extracted yet |
| Rosar 2024 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 | not stated | 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 | not stated | not extracted yet |
| Afshar-Oromieh 2017 Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095. PMID:28280855 | 2017 | this review only | not stated | not extracted yet |
| Al-Ibraheem 2024 From Despair to Hope: First Arabic Experience of 177Lu-PSMA and 161Tb-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer. PMID:38893095 | 2024 | this review only | not stated | not extracted yet |
| Alan-Selcuk 2023 Clinical Experience with [225Ac]Ac-PSMA Treatment in Patients with [177Lu]Lu-PSMA-Refractory Metastatic Castration-Resistant Prostate… PMID:37620050 | 2023 | this review only | not stated | not extracted yet |
| Ballal 2023 Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic… PMID:37462775 | 2023 | this review only | not stated | not extracted yet |
| Buteau 2025 First-in-human results of terbium-161 [161Tb]Tb-PSMA-I&T dual beta–Auger radioligand therapy in patients with metastatic… DOI:10.1016/s1470-2045(25)00332-8 | 2025 | this review only | not stated | not extracted yet |
| Buteau 2025 First-in-human results of terbium-161 [161Tb]Tb-PSMA-I&T dual beta-Auger radioligand therapy in patients with metastatic… PMID:40617237 | 2025 | this review only | not stated | not extracted yet |
| Feuerecker 2023 Comparative Analysis of Morphological and Functional Effects of 225Ac- and 177Lu-PSMA Radioligand Therapies (RLTs) on Salivary Glands. PMID:38069166 | 2023 | this review only | not stated | not extracted yet |
| Kratochwil 2017 Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Dosimetry Estimate and Empiric Dose Finding. PMID:28408529 | 2017 | this review only | not stated | not extracted yet |
| Kratochwil 2018 Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Swimmer-Plot Analysis Suggests Efficacy… PMID:29326358 | 2018 | this review only | not stated | not extracted yet |
| Kucuk 2025 Initial Multicenter Experience with [161Tb]Tb-PSMA in [177Lu]Lu-PSMA-Refractory Metastatic Castration-Resistant Prostate Cancer:… PMID:41043996 | 2025 | this review only | not stated | not extracted yet |
| Laccetti 2023 A Phase 1, Open-label, Dose-Ascending Study to Evaluate the Safety and Tolerability of the Therapeutic Radiopharmaceutical 131I-MIP-1095… PMID:37812518 | 2023 | this review only | not stated | not extracted yet |
| Liu 2024 A phase 2, single-arm trial evaluating 131 I-PSMA-1095 targeted radioligand therapy for metastatic castration-resistant prostate cancer. PMID:38726601 | 2024 | this review only | not stated | not extracted yet |
| Ma 2025 The efficacy and safety of 225Ac-PSMA-617 in metastatic castration-resistant prostate cancer. PMID:40094004 | 2025 | this review only | not stated | not extracted yet |
| Perrone 2025 Long-Term Safety and Survival Outcomes of [225Ac]Ac-PSMA (Prostate-Specific Membrane Antigen) and [225Ac]Ac-/[177Lu]Lu-PSMA (TANDEM)… PMID:39941774 | 2025 | this review only | not stated | not extracted yet |
| Rosar 2025 Pilot experience of [161Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry. PMID:40963912 | 2025 | this review only | not stated | not extracted yet |
| Sanli 2021 225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer: A Single-Center Experience. PMID:34593693 | 2021 | this review only | not stated | not extracted yet |
| Satapathy 2020 Evolving role of 225Ac-PSMA radioligand therapy in metastatic castration-resistant prostate cancer-a systematic review and meta-analysis. PMID:33746213 | 2021 | this review only | not stated | not extracted yet |
| Sathekge 2019 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study. PMID:30232539 | 2019 | this review only | not stated | not extracted yet |
| Sathekge 2020 Predictors of Overall and Disease-Free Survival in Metastatic Castration-Resistant Prostate Cancer Patients Receiving 225Ac-PSMA-617… PMID:31101746 | 2020 | this review only | not stated | not extracted yet |
| Sathekge 2022 mCRPC Patients Receiving 225Ac-PSMA-617 Therapy in the Post-Androgen Deprivation Therapy Setting: Response to Treatment and Survival… PMID:35177427 | 2022 | this review only | not stated | not extracted yet |
| Sathekge 2023 225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings. PMID:36864360 | 2023 | this review only | not stated | not extracted yet |
| Sathekge 2024 Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study. PMID:38218192 | 2024 | this review only | not stated | not extracted yet |
| Schaefer-Schuler 2023 [161Tb]Tb-PSMA-617 radioligand therapy in patients with mCRPC: preliminary dosimetry results and intra-individual head-to-head comparison… PMID:38505615 | 2024 | this review only | not stated | not extracted yet |
| Sen 2021 Therapeutic efficacy of 225Ac-PSMA-617 targeted alpha therapy in patients of metastatic castrate resistant prostate cancer after… PMID:34059998 | 2021 | this review only | not stated | not extracted yet |
| Van der Doelen 2021 Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with 225Ac-PSMA-617… PMID:33353867 | 2021 | this review only | not stated | not extracted yet |
| Widjaja 2025 Refining the clinical utility of [177Lu]Lu/[225Ac]Ac-PSMA tandem RLT in patients with metastatic castration resistant prostate cancer. PMID:41174098 | 2026 | this review only | not stated | not extracted yet |
| Yadav 2020 Efficacy and safety of 225Ac-PSMA-617 targeted alpha therapy in metastatic castration-resistant Prostate Cancer patients. PMID:32802197 | 2020 | this review only | not stated | not extracted yet |
| Zacherl 2021 First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients. PMID:33008928 | 2021 | this review only | not stated | 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 |
|---|---|---|
| Therapeutic outcomes of ²²⁵Ac/¹⁷⁷Lu-PSMA combination therapy in advanced metastatic Castration-Resistant prostate cancer: A systematic… (2026) | 6 | 0.17 |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with metastatic castration-resistant prostate cancer (mCRPC) | mCRPC patients, median age 62 to 77 years (33 studies, 1525 patients, 3625 therapy cycles) |
| Intervention | PSMA radioligand therapy beyond [177Lu]Lu-PSMA monotherapy ([225Ac]Ac-PSMA, [177Lu]Lu/[225Ac]Ac-PSMA tandem, [161Tb]Tb-PSMA, [131I]PSMA) | [225Ac]Ac-PSMA monotherapy (17 studies); [177Lu]Lu/[225Ac]Ac-PSMA tandem (7 to 8 studies); [161Tb]Tb-PSMA (5 studies); [131I]PSMA (3 studies) |
| Comparison | Not specified | No comparator (single-arm studies) |
| Outcomes | Objective response rate, disease control rate, toxicity outcomes | Disease control rate and objective response rate (31 studies, 1406 patients); adverse events (32 studies, 1390 patients) |
| Study designs | Original clinical studies; excluded duplicates, non-original reports, book chapters, editorials, conference materials, preclinical, dosimetry studies | 25 retrospective and 8 prospective studies |
| Timing | Not specified | Not specified |