The PROPHECY trial: Multicenter prospective trial of circulating tumor cell (CTC) AR-V7 detection in men with mCRPC receiving abiraterone (A) or enzalutamide (E).

AR-V7 and treatment selection in advanced prostate cancer: are we there yet?

“…Ideally, prior to definitive incorporation of AR-V7 testing as a predictive biomarker for treatment selection in CRPC, these results must be validated in a prospective trial. Towards this end, the initial results of the first prospective biomarker trial with the primary goal of validating AR-V7 as a predictive marker for achieving benefit with ARSi have been recently reported at the 2018 American Society of Clinical Oncology (ASCO) annual meeting (9). This study, called the PROPHECY trial (“Multicenter prospective trial of circulating tumor cell AR-V7 detection in men with CRPC receiving abiraterone or enzalutamide”) included 118 men with progressive, high-risk chemotherapy-naïve metastatic CRPC, who first received abiraterone or enzalutamide (by physician’s choice) until disease progression, followed by taxane chemotherapy.…”

Rapidly evolving treatment paradigm and considerations for sequencing therapies in metastatic prostate cancer—a narrative review

“…In a cross-sectional cohort study of 161 mCRPC patients, patients with AR-V7 negative circulating tumor cells (CTCs) (as determined by Oncotype DX AR-V7 Nuclear Detect test) (38), superior OS was seen with taxanes compared to NAA when AR-V7-positive CTCs were detected pre-therapy (HR 0.24; 95% CI: 0.10-0.57; P=0.035). In the PROPHECY trial, AR-V7 detection (as determined by both Hopkins modified-Adna Test CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear AR-V7 protein assay) was found to be associated with a shorter PFS (3.1 vs. 7.3 months for AR-V7 positive vs. AR-V7 negative groups as determined by the Hopkins test and 3.1 vs. 6 months for AR-V7 positive vs. negative groups as determined by the Epic test) and OS (11.5 vs. 25.5 months for AR-V7 positive vs. negative groups as determined by the Hopkins test and 8.4 vs. 25.5 months for AR-V7 positive vs. negative groups as determined by the Epic test) in mCRPC patients treated with abiraterone or enzalutamide (39). A key limitation prohibiting widespread adoption of AR-V7 in clinical practice is that second NAA therapy is typically well tolerated and AR-V7 testing itself can be expensive, associated with logistical challenges (may take a few weeks to result), and may not ultimately rule out a treatment response.…”

Clinical Relevance of Circulating Tumor Cells in Prostate Cancer Management

“…The results of the studies mentioned above, as well as the data provided by other authors [ 94 , 95 ] led to the first approval of CTC as a predictive biomarker to guide the choice of a taxane versus an androgen receptor signaling inhibitor (ARSi) in the second-line or greater setting. While the presence of ARV7 mRNA and ARV7 protein in CTC can be considered a blood-based biomarker to predict de novo or developed resistance to andro- gen pathway-targeted therapies [ 96 ], this method is not free from potential drawbacks. Importantly, the ARV7 status can change during the course of antiandrogen therapy [ 97 , 98 , 99 ], and the ARV7 status in individual CTCs from the same patient is heterogeneous [ 100 ].…”

“…Theoretically suitable for the identification of patients with occult disseminated disease CTC rarely found in patients with localized PC [75][76][77] CTC number does not seem to correlate with other clinicopathological parameters [75][76][77][78][79] Discrepancies in the CTC numbers obtained with various methods negatively affect cost-effectiveness of this parameter [81][82][83][84] Source of the genetic material of PC CTC mirror accurately genetic status of cancer cells found in biopsy specimens [89] Genetic status of CRC was shown to be a predictor of prostate cancer aggressiveness [103] and therapeutic responses [90][91][92][93][94][95][96][97][98][99][100][101][102] Not enough evidence confirming superiority of this method over conventional biopsy Institutional Review Board Statement: Not applicable.…”