Plasma and urine biomarker algorithm versus systematic biopsy for prostate cancer detection in elderly men: a randomised trial with early termination for futility

OBJECTIVE: This study aimed to compare test sensitivity for detecting aggressive prostate cancer and test specificity (measured by reduction in prostate biopsies) between algorithm-triage and standard systematic biopsy in elderly men with suspected prostate cancer. METHODS: This randomised controlled trial enrolled men ≥ 70 years old suspected of prostate cancer and randomised them 1:1 to algorithm-triage or standard systematic biopsies. The algorithm arm used a 10-gene mRNA panel from urine and plasma samples, integrated with clinical characteristics and PSA measurements to predict prostate cancer with International Society of Urological Pathology grade group ≥ 2. Patient-reported outcomes measures were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores or subdomains throughout a 24-month follow-up. CLINICALTRIALS: gov: NCT04079699. RESULTS: A total of 202 men were included between October 2019 and September 2021. The study was terminated early due to algorithm underperformance. The algorithm-triage arm detected fewer indolent cancers (7.9% vs. 19%, absolute difference -10.9 percentage points, 95% confidence interval [CI]: -21.0 to -1.0 pp, P = 0.039) but also fewer clinically significant cancers (26% vs. 40%, absolute difference -13.9 percentage points, 95% CI: -27.6 to -0.1 pp, P = 0.051) compared to systematic biopsy. Patient-reported outcomes showed no significant between-group differences in FACT-P scores or subdomains throughout 24-month follow-up (differences 0.1-2.2 points, all P > 0.05), indicating comparable quality of life. CONCLUSION: The biomarker-based algorithm-triage reduced biopsy numbers but also detected fewer -clinically significant prostate cancers. Quality of life was comparable between approaches.