| Autor: |
Edmond M, Kwan, Heidi, Fettke, Megan, Crumbaker, Maria M, Docanto, Sarah Q, To, Patricia, Bukczynska, Andrew, Mant, Nicole, Ng, Siavash, Foroughi, Lisa-Jane K, Graham, Anne-Maree, Haynes, Sarah, Azer, Lisi Elizabeth, Lim, Eva, Segelov, Kate, Mahon, Ian D, Davis, Phillip, Parente, Carmel, Pezaro, Tilman, Todenhöfer, Niranjan, Sathianathen, Christine, Hauser, Lisa G, Horvath, Anthony M, Joshua, Arun A, Azad |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Transl Androl Urol |
| ISSN: |
2223-4691 |
| Popis: |
BACKGROUND: As potent systemic therapies transition earlier in the prostate cancer disease course, molecular biomarkers are needed to guide optimal treatment selection for metastatic hormone-sensitive prostate cancer (mHSPC). The value of whole blood RNA to detect candidate biomarkers in mHSPC remains largely undefined. METHODS: In this cohort study, we used a previously optimised whole blood reverse transcription polymerase chain reaction assay to assess the prognostic utility [measured by seven-month undetectable prostate-specific antigen (PSA) and time to castration-resistance (TTCR)] of eight prostate cancer-associated gene transcripts in 43 mHSPC patients. Transcripts with statistically significant associations (P50% response (PSA(50)), progression-free survival (PFS) and overall survival (OS). Clinical outcomes were prospectively collected in a protected digital database. Kaplan-Meier estimates and multivariable Cox proportional-hazards models assessed associations between gene transcripts and clinical outcomes (mHSPC covariates: disease volume, docetaxel use and haemoglobin level; mCRPC covariates: prior exposure to chemotherapy or ARPIs, haemoglobin, performance status and presence of visceral disease). Follow-up was performed monthly during ARPI treatment, three-weekly during taxane chemotherapy, and three-monthly during androgen deprivation therapy (ADT) monotherapy. Serial PSA measurements were performed before each follow-up visit and repeat imaging was at the discretion of the investigator. RESULTS: Detection of circulating Grainyhead-like 2 (GRHL2) transcript was associated with poor outcomes in mHSPC and mCRPC patients. Detectable GRHL2 expression in mHSPC was associated with a lower rate of seven-month undetectable PSA levels (25% vs. 65%, P=0.059), and independently associated with shorter TTCR (HR 7.3, 95% CI: 1.5–36, P=0.01). In the mCRPC cohort, GRHL2 expression predicted significantly lower PSA(50) response rates (46% vs. 69%, P=0.01), and was independently associated with shorter PFS (HR 3.1, 95% CI: 1.8–5.2, P |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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