Clinical and genomic characterization of Low PSA Secretors: a unique subset of metastatic castration resistant prostate cancer.
Adenocarcinoma
/ blood
Aged
Aged, 80 and over
Biomarkers, Tumor
/ blood
Biopsy
DNA, Neoplasm
/ genetics
Disease-Free Survival
Female
Follow-Up Studies
Genomics
Humans
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Prostate-Specific Antigen
/ blood
Prostatic Neoplasms, Castration-Resistant
/ blood
Retinoblastoma Binding Proteins
/ genetics
Retrospective Studies
Tumor Suppressor Protein p53
/ genetics
Ubiquitin-Protein Ligases
/ genetics
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
10
01
2020
accepted:
20
03
2020
revised:
29
02
2020
pubmed:
15
4
2020
medline:
25
11
2021
entrez:
15
4
2020
Statut:
ppublish
Résumé
Metastatic disease burden out of proportion to serum PSA has been used as a marker of aggressive phenotype prostate cancer but is not well defined as a distinct subgroup. We sought to prospectively characterize the molecular features and clinical outcomes of Low PSA Secretors. Eligible metastatic castration resistant prostate cancer (mCRPC) patients without prior small cell histology underwent metastatic tumor biopsy with molecular characterization. Low PSA secretion was defined as serum PSA < 2, 5, or 10 ng/mL plus >5 metastases with radiographic progression at study entry. Clinical and molecular features were compared between low PSA vs. normal secretors in a post-hoc fashion. 183 patients were enrolled, including 15 (8%) identified as Low PSA Secretors using optimal PSA cut point of 5 ng/mL. Biopsies from Low PSA Secretors demonstrated higher t-SCNC and RB1 loss and lower AR transcriptional signature scores compared with normal secretors. Genomic loss of RB1 and/or TP53 was more common in Low PSA Secretors (80% vs. 41%). Overall survival (OS) was shorter in Low PSA Secretors (median OS = 26.7 vs. 46.0 months, hazard ratio = 2.465 (95% CI: 0.982-6.183). Progression-free survival (PFS) on post-biopsy treatment with AR-targeted therapy was shorter than with chemotherapy (median PFS 6.2 vs. 4.1 months). Low PSA secretion in relation to metastatic tumor burden may be a readily available clinical selection tool for de-differentiated mCRPC with molecular features consistent with t-SCNC. Prospective validation is warranted.
Sections du résumé
BACKGROUND
Metastatic disease burden out of proportion to serum PSA has been used as a marker of aggressive phenotype prostate cancer but is not well defined as a distinct subgroup. We sought to prospectively characterize the molecular features and clinical outcomes of Low PSA Secretors.
METHODS
Eligible metastatic castration resistant prostate cancer (mCRPC) patients without prior small cell histology underwent metastatic tumor biopsy with molecular characterization. Low PSA secretion was defined as serum PSA < 2, 5, or 10 ng/mL plus >5 metastases with radiographic progression at study entry. Clinical and molecular features were compared between low PSA vs. normal secretors in a post-hoc fashion.
RESULTS
183 patients were enrolled, including 15 (8%) identified as Low PSA Secretors using optimal PSA cut point of 5 ng/mL. Biopsies from Low PSA Secretors demonstrated higher t-SCNC and RB1 loss and lower AR transcriptional signature scores compared with normal secretors. Genomic loss of RB1 and/or TP53 was more common in Low PSA Secretors (80% vs. 41%). Overall survival (OS) was shorter in Low PSA Secretors (median OS = 26.7 vs. 46.0 months, hazard ratio = 2.465 (95% CI: 0.982-6.183). Progression-free survival (PFS) on post-biopsy treatment with AR-targeted therapy was shorter than with chemotherapy (median PFS 6.2 vs. 4.1 months).
CONCLUSIONS
Low PSA secretion in relation to metastatic tumor burden may be a readily available clinical selection tool for de-differentiated mCRPC with molecular features consistent with t-SCNC. Prospective validation is warranted.
Identifiants
pubmed: 32286548
doi: 10.1038/s41391-020-0228-0
pii: 10.1038/s41391-020-0228-0
doi:
Substances chimiques
Biomarkers, Tumor
0
DNA, Neoplasm
0
RB1 protein, human
0
Retinoblastoma Binding Proteins
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Prostate-Specific Antigen
EC 3.4.21.77
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
81-87Références
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