Table 1.
Summary of the main findings reported in the selected manuscripts.
| Source | Year/Location | Study Design | Sample Size | Demographic Data (Median) | Radiopharmaceutical | Most Common Mutations |
Response | Outcome | DDR Impact (Y/N) |
Comment |
|---|---|---|---|---|---|---|---|---|---|---|
| Isaacsson et al. [19] | 2019/USA | Retrospective | 28 (10 HR+, 35.7%) |
Age: 66 yr, Baseline PSA: 77.1 ng/mL, Baseline ALP: 130 U/L |
223Ra-therapy | Not specified | ALP response within 12 weeks: 64%, with a significantly higher response rate in HR+ patients | More favorable outcome was registered in HR+ than in HR- subjects (OS 36.9 vs. 19.0 mo) | Y | PCa patients harboring mutations in HR genes showed a higher response rate and more prolonged survival after 223Ra-therapy |
| van der Doelen et al. [20] | 2020/ The Netherlands + USA |
2-centre retrospective study |
93 (28 DDR+, 30.1%) |
Age: 68 yr, Baseline PSA: 59.0 ng/mL, Baseline ALP: 124 U/L |
223Ra-therapy | ATM, BRCA2, CDK-12 | PSA response: 29.4% in DDR+ vs. 34.6% in DDR-ALP response: 33.0% in DDR+ versus −35.0% in DDR- |
OS of the overall cohort: 21 mo DDR+ pts had longer OS than DDR- (median 36.3 vs. 17.0 mo) |
Y | Patients harboring DDR alterations had a more favorable outcome after 223Ra-therapy. Time to ALP progression (TAP) and time to subsequent treatment (TST) resulted also longer in DDR+ patients than in DDR- ones |
| Kratochwil et al. [21] | 2020/ Germany |
Retrospective | 10 (7 DDR+, 70%) |
Age: not available, Baseline PSA: 481 ng/mL |
[225Ac]Ac-PSMA-617 | TP53, CHEk2, ATM | The study was carried out in non-responders | Not specified | Not assessed | Patients resistant to radioligand therapy with [225Ac]Ac-PSMA-617 often harbor mutations in DDR genes |
| Privé et al. [22] | 2021/ The Netherlands |
Observational cohort | 40 (17 DDR+, 42.5%) |
Age: 61 yr, Baseline PSA: not available |
[177Lu/225Ac]-PSMA-617 or PSMA-I&T | BRCA 1/2 | No significant differences in PSA response (59% in DDR+ vs. 65% in DDR-) | No OS difference among DDR + patients vs. DDR- patients (median OS 11.1 vs. 10.7 mo) |
N | DDR defects did not show any significant impact on mCRPC patients’ response to PSMA-targeted therapy with beta or alpha emitters |
| Liu et al. [23] | 2022/ USA |
Two-center retrospective study |
127 (127 DDR+) |
Age: 61 yr, Baseline PSA: 21 ng/mL, Baseline ALP: 123 U/L |
223Ra-therapy | TP53, BRCA 1/2, PTEN | PSA response (entire cohort): 22.6%ALP response (entire cohort): 69.8% | TMPRSS2-ERG mutation was associated with a lower OS (15.4 mo), while RB deletion with a shorter PFS (6 mo). | N | DDR mutations did not represent a predictive factor on response to 223Ra-therapy, although certain mutations resulted associated with a trend towards a worse prognosis |
| van der Doelen et al. [24] | 2022/ The Netherlans + Germany |
Observational cohort |
13 (2 DDR+, 15.3%) |
Age: 71 yr, Baseline PSA: 878 ng/mL, Baseline ALP: 356 U/L |
[225Ac]Ac-PSMA-617 | BRCA1 | PSA response (entire cohort): 69%, ALP response: 62%, RECIST response: 50%, PERCIST response: 86% |
OS (entire cohort): 8.5 mo, | Y | Patients harboring DDR defects present a trend toward a longer OS after therapy than those without mutations |
| Satapathy et al. [25] | 2022/ india |
Retrospective | 15 (10 DDR+, 66.6%) |
Age: 66 yr, Baseline PSA: 87 ng/mL |
[177Lu]Lu-PSMA-617 (n = 3) | ATM, BRCA2, TP53 | PSA response (entire cohort): 26.7% RECIST response: 12.5% |
PFS (entire cohort): 3 mo, OS (entire cohort): 6 mo | N | DDR defects did not impact either on final outcome or theapy-response of mCRPC patients submitted to RLT |
Abbreviations: DDR—DNA damage repair; HR—homologous recombination; yr—years; ALP—alkaline phosphatase; PSA—prostate specific antigen; PSMA —prostate specific membrane antigen; OS—overall survival; PFS—progression free survival; mo—months; Y—yes; N—no.