Genomic classifier score linked with focal therapy outcomes in prostate cancer

Data from a post-hoc analysis of a phase 2 trial suggest that a genomic classifier (GC) score obtained from diagnostic biopsy may be able to predict focal therapy outcomes in patients with prostate cancer.¹

The study, reported in JCO Precision Oncology, looked at the association between treatment failure after focal cryotherapy and Decipher score, a tumor-based GC.

“Focal therapy of prostate cancer (PCa) is of increasing interest because it may provide cancer cure while preserving quality of life,” the authors explained. “However, within 2 years of treatment, up to one third of patients undergoing focal therapy experience disease recurrence.”

The Decipher score has been previously validated as a prognostic marker for patients undergoing radical prostatectomy and radiation therapy. Thus, the authors sought to assess its clinical applications in prognosticating outcomes for patients undergoing focal therapy.

For the study, the investigators retrospectively assessed 108 patients with unilateral grade group 2 to 4 prostate cancer who underwent hemigland cryoablation of the prostate between 2017 and 2021. Biopsy samples were obtained from a phase 2 study (NCT03503643) conducted at the University of California, Los Angeles.

According to the authors, “Pretreatment biopsy tissue was subjected to transcriptomic profiling to generate GC scores.” The Decipher score ranges from 0 to 1, characterizing patients as either low-risk (less than 0.45) or high-risk (0.45 or higher).

The median GC score in the cohort was 0.34, and 66% of patients had a GC less than 0.45 (low-risk).

Treatment failure at 6-month biopsy occurred in 46% of patients in the GC high-risk group vs 21% of patients in the GC low-risk group (OR, 2.61; 95% CI, 1.05 to 6.51; P = .04). This difference remained statistically significant at 18 months, with treatment failure rates of 76% vs 44% (OR, 3.58; 95% CI, 1.37 to 9.36; P = .009).

When GC score was treated as a continuous variable, higher scores remained associated with increased odds of treatment failure, although the association did not reach statistical significance.

Further, data showed that nonluminal differentiated tumors (n = 70) were associated with higher odds of treatment failure compared with luminal differentiated tumors (37% vs 16%, respectively; OR, 2.87; 95% CI, 1.01 to 8.11; P = .047). This trend was similar at 18 months, although not statistically significant.

The authors noted that further work is needed to confirm the clinical use of the GC in guiding focal therapy decisions.

Overall, they concluded “While focal therapy for PCa may offer oncologic benefits with fewer adverse effects, the rate of treatment failure remains appreciable. A GC based on biopsy tissue identified patients at an increased risk of treatment failure, beyond clinicopathologic variables. Thus, GC may be useful in predicting focal therapy outcomes and counseling patients on treatment failure risk.”

REFERENCE

1. Weiner AB, Proudfoot JA, Aker M, et al. Genomic Biomarker for Prostate Cancer Focal Therapy: Post Hoc Assessment of a Phase II Clinical Trial. JCO Precis Oncol. 2025:9:e2500535. doi:10.1200/PO-25-00535