PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 05 2023
15 05 2023
Historique:
received:
11
11
2022
revised:
24
01
2023
accepted:
28
02
2023
medline:
16
5
2023
pubmed:
11
3
2023
entrez:
10
3
2023
Statut:
ppublish
Résumé
In men with metastatic castration-resistant prostate cancer (mCRPC), prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has drastically improved clinical outcomes. A liquid biopsy characterizing PSMA expression could be useful in guiding optimal therapy. We conducted a retrospective analysis of the prospective multicenter PROPHECY (Prospective CiRculating PrOstate Cancer Predictors in HighEr Risk mCRPC StudY) trial of men with mCRPC (n = 118) treated with abiraterone (abi) or enzalutamide (enza). Circulating tumor cells (CTC) were enriched (CTC/mL) and characterized for PSMA protein expression/heterogeneity at baseline and progression. We utilized proportional hazards modeling of the association between PSMA-positive (PSMA+) CTC enumeration with overall survival (OS) and progression-free survival (PFS). Overall, 97 men with mCRPC had evaluable blood samples for baseline CTC PSMA detection; 78 men (80%) had detectable CTCs. Of these, 55% (43/78) of men had any PSMA CTC detection, 21% (16/78) had ≥2 PSMA+ CTCs/mL, and 19% (8/43) were 100% PSMA+. At progression on abi/enza, 88% (50/57) of men had detectable CTCs, 68% (34/50) had any PSMA CTCs, and 12% (4/34) had 100% PSMA+ CTCs. Among paired cases (n = 57), PSMA+ CTC detection increased slightly after abi/enza progression. Using an optimal cutoff of ≥2 PSMA+ CTCs/mL, median OS was 26, 21, and 11 months for men without CTCs, PSMA- CTCs, and PSMA+ CTCs. Adjusting for prior abi/enza therapy, Halabi clinical risk score, and CTC enumeration, the HRs for OS and PFS for PSMA+ CTC+ were 3.0 [95% confidence interval (CI) = 1.1-7.8] and 2.3 (95% CI = 0.9-5.8). We observed PSMA CTC heterogeneity between and within patients with mCRPC over time during abi/enza progression. CTC PSMA enumeration was adversely prognostic independent of clinical factors and disease burden. Further validation is warranted in the context of PSMA-targeted therapies.
Identifiants
pubmed: 36897758
pii: 718681
doi: 10.1158/1078-0432.CCR-22-3233
pmc: PMC10192124
mid: NIHMS1890682
doi:
Substances chimiques
abiraterone
G819A456D0
enzalutamide
93T0T9GKNU
Biomarkers, Tumor
0
Types de publication
Multicenter Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1929-1937Subventions
Organisme : NCI NIH HHS
ID : R01 CA233585
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Informations de copyright
©2023 American Association for Cancer Research.
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