Role of Circulating Tumor Cells (CTC), Androgen Receptor Full Length (AR-FL) and Androgen Receptor Splice Variant 7 (AR-V7) in a Prospective Cohort of Castration-Resistant Metastatic Prostate Cancer Patients.
AR-FL
AR-V7
castration-resistant prostate cancer
circulating tumor cells
prognostic biomarkers
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
13 Sep 2019
13 Sep 2019
Historique:
received:
19
07
2019
revised:
06
09
2019
accepted:
10
09
2019
entrez:
22
9
2019
pubmed:
22
9
2019
medline:
22
9
2019
Statut:
epublish
Résumé
Circulating tumor cells (CTC), androgen receptor full-length (AR-FL), and androgen receptor splice variant 7 (AR-V7) are prognostic in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). AR-V7 seems to predict resistance to androgen-receptor signaling inhibitors (ARSi). We assessed the association of CTC, AR-FL, and AR-V7 with prostate-specific antigen (PSA) response and overall survival (OS). We used a modified AdnaTest CTC-based AR-FL and AR-V7 mRNA assay. Chi-square test, Fisher Exact test, Kaplan-Meier method, log-rank test, Cox proportional hazards models were used as appropriate. We enrolled 39 mCRPC pts, of those 24 started a first-line treatment for mCRPC (1L subgroup) and 15 had received at least two lines for mCRPC (>2L subgroup). CTC, AR-FL, and AR-V7 were enriched in >2L compared to 1L subgroup. Detection of these biomarkers was associated with a lower percentage of biochemical responses. Only 1/7 AR-V7+ pts had a PSA response and received cabazitaxel. Median OS was 4.7 months (95% CI 0.6-8.9) in AR-V7+ pts and not reached in AR-V7- pts. AR-V7 was the only variable with prognostic significance in the Cox model. AR-V7, CTC, and AR-FL are associated with advanced mCRPC and AR-V7+ predicts for shorter OS.
Sections du résumé
BACKGROUND
BACKGROUND
Circulating tumor cells (CTC), androgen receptor full-length (AR-FL), and androgen receptor splice variant 7 (AR-V7) are prognostic in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). AR-V7 seems to predict resistance to androgen-receptor signaling inhibitors (ARSi).
METHODS
METHODS
We assessed the association of CTC, AR-FL, and AR-V7 with prostate-specific antigen (PSA) response and overall survival (OS). We used a modified AdnaTest CTC-based AR-FL and AR-V7 mRNA assay. Chi-square test, Fisher Exact test, Kaplan-Meier method, log-rank test, Cox proportional hazards models were used as appropriate.
RESULTS
RESULTS
We enrolled 39 mCRPC pts, of those 24 started a first-line treatment for mCRPC (1L subgroup) and 15 had received at least two lines for mCRPC (>2L subgroup). CTC, AR-FL, and AR-V7 were enriched in >2L compared to 1L subgroup. Detection of these biomarkers was associated with a lower percentage of biochemical responses. Only 1/7 AR-V7+ pts had a PSA response and received cabazitaxel. Median OS was 4.7 months (95% CI 0.6-8.9) in AR-V7+ pts and not reached in AR-V7- pts. AR-V7 was the only variable with prognostic significance in the Cox model.
CONCLUSION
CONCLUSIONS
AR-V7, CTC, and AR-FL are associated with advanced mCRPC and AR-V7+ predicts for shorter OS.
Identifiants
pubmed: 31540293
pii: cancers11091365
doi: 10.3390/cancers11091365
pmc: PMC6770005
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Clin Cancer Res. 2017 Feb 1;23(3):726-734
pubmed: 27489290
J Clin Invest. 2019 Jan 2;129(1):192-208
pubmed: 30334814
Prostate. 2019 Jan;79(1):54-61
pubmed: 30141201
J Clin Oncol. 2019 May 1;37(13):1120-1129
pubmed: 30865549
Br J Cancer. 2015 May 12;112(10):1717-24
pubmed: 25897673
Eur Urol. 2018 May;73(5):715-723
pubmed: 29258679
Eur Urol. 2018 May;73(5):727-735
pubmed: 28866255
N Engl J Med. 2014 Sep 11;371(11):1028-38
pubmed: 25184630
Eur Urol. 2019 Mar;75(3):368-373
pubmed: 30773204
JAMA Oncol. 2015 Aug;1(5):582-91
pubmed: 26181238
N Engl J Med. 2018 Feb 15;378(7):645-657
pubmed: 29412780
BJU Int. 2019 Oct;124(4):693-700
pubmed: 31055861
Stat Med. 1996 Feb 28;15(4):361-87
pubmed: 8668867
Ann Oncol. 2017 Jul 01;28(7):1508-1516
pubmed: 28472366
JAMA Oncol. 2016 Nov 01;2(11):1441-1449
pubmed: 27262168
Nat Rev Clin Oncol. 2018 Nov;15(11):663-675
pubmed: 30135575
Oncotarget. 2016 Jun 21;7(25):37839-37845
pubmed: 27191887
JAMA Oncol. 2018 Sep 1;4(9):1179-1186
pubmed: 29955787
Eur Urol. 2019 Nov;76(5):676-685
pubmed: 31036442
J Clin Oncol. 2017 Jul 1;35(19):2149-2156
pubmed: 28384066
J Urol. 2017 Jan;197(1):135-142
pubmed: 27436429
Eur Urol. 2017 Jun;71(6):874-882
pubmed: 27979426
Cancer Treat Rev. 2019 Dec;81:101871
pubmed: 31698174