Biomarker Linked to Poorer Survival Outcomes in Castration-Resistant Prostate Cancer

Androgen receptor variant 7 (AR-V7) detected via liquid biopsy was significantly associated with poorer survival outcomes in patients with castration-resistant prostate cancer, according to findings published in Frontiers in Oncology.

“Liquid biopsy is emerging as a reliable source of biological data for biomarker discovery, especially in advanced prostate cancer when tissue biopsy is often not obtainable,” researchers wrote. “In [castration-resistant prostate cancer], one of most promising prognostic markers is the constitutively active AR splice variant 7 (AR-V7).”

The systematic review and meta-analysis included 37 studies from Embase, Medline, and Scopus databases up to September 2021.  

In patients treated with androgen receptor signaling inhibitors (enzalutamide or abiraterone), AR-V7 positivity was linked to significantly poorer overall survival (HR 4.34, 95% CI 3-6.28, P<.00001), progression-free survival (HR 2.89, 95% CI 2.15-3.87, P<.00001), and prostate-specific antigen progression-free survival (HR 4.69, 95% CI 2.5-8.82, P<.0001) compared to AR-V7 negativity.

In patients treated with taxane-based chemotherapy, AR-V7 positivity was associated with poorer overall survival (HR 1.7, 95% CI 1.03-2.81, P=.04). Researchers reported no conclusive findings regarding progression-free survival and prostate-specific antigen progression-free survival, as data for this population only spanned 2 studies and 129 patients.

Patients with AR-V7 positivity had superior overall survival with taxane chemotherapy than with androgen receptor signaling inhibitors (HR .54, 95% CI .34-.87, P=.01). However, overall survival was not significantly different between patients receiving either type of therapy when AR-V7 was negative.

Additionally, patients with AR-V7 positivity receiving other treatments had worse overall survival (HR 3.47, 95% CI 1.85-6.49, P=.0001, 5 studies) and progression-free survival (HR 1.68, 95% CI 1.03-2.76, P=.04, 3 studies).

“Standardization of liquid biopsy AR-V7 detection would underpin utility in clinical practice. Avoiding ineffective therapies or early switching to more effective approaches should ensure better outcomes for patients,” authors concluded, adding that more research is needed to directly compare chemotherapy with androgen receptor signaling inhibitors.

Reference:
Khan T, Becker TM, Scott KF, et al. Prognostic and predictive value of liquid biopsy-derived androgen receptor variant 7 (AR-V7) in prostate cancer: A systematic review and meta-analysis. Front Oncol. Published online March 18, 2022. doi:10.3389/fonc.2022.868031