Abstract
Circulating RNAs extracted from liquid biopsies represent a promising source of cancer‐ and therapy‐related biomarkers. We screened whole blood from patients with metastatic castration‐resistant prostate cancer (mCRPC) following their first‐line treatment with abiraterone acetate and prednisone (AA‐P) to identify circulating RNAs that may correlate with progression‐free survival (PFS). In a prospective multicenter observational study, 53 patients with mCRPC were included after they started first‐line AA‐P treatment. Blood was drawn at baseline, 1, 3, and 6 months after treatment initiation. The levels of predefined circulating RNAs earlier identified as being upregulated in patients with mCRPC (e.g., microRNAs, long noncoding RNAs, and mRNAs), were analyzed. Uni‐ and multivariable Cox regression and Kaplan–Meier analyses were used to analyze the prognostic value of the various circulating RNAs for PFS along treatment. Detectable levels of kallikrein‐related peptidase 3 (KLK3) mRNA at baseline were demonstrated to be an independent prognostic marker for PFS (201 vs 501 days, P = 0.00054). Three months after AA‐P treatment initiation, KLK3 could not be detected in the blood of responding patients, but was still detectable in 56% of the patients with early progression. Our study confirmed that KLK3 mRNA detection in whole blood is an independent prognostic marker in mCRPC patients receiving AA‐P treatment. Furthermore, the levels of circulating KLK3 mRNA in patients receiving AA‐P treatment might reflect treatment response or early signs of progression.
Highlights
Prostate cancer (PCa) is the second most common cancer in men worldwide [1]
Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
Four patients were excluded [two patients stopped directly, one patient stopped before the second visit, and one patient did not meet with the inclusion criteria]
Summary
Prostate cancer (PCa) is the second most common cancer in men worldwide [1]. It presents with a wide range of disease stages, from localized PCa to lethal metastatic castration-resistant prostate cancer (mCRPC). The therapeutic landscape for patients with mCRPC is rapidly evolving, with several new therapies improving overall survival (OS). Abiraterone acetate and prednisone (AA-P) is one of these therapies that has been proven to prolong OS in patients with mCRPC [2,3]. Suboptimal response [de novo resistance or shorter progression-free survival (PFS)] has been observed in a subset of patients and eventually all patients develop therapy resistance. To improve outcome and cost-effectiveness, it is important to select patients for treatment with AA-P that will benefit most
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