Low PSA Free-to-Total Ratio Improves Detection of Clinically Significant Prostate Cancer in Men with Low PSA Levels: Study

"A lower PSA FTR of ≤0.15 was linked to an increased likelihood of clinically significant prostate cancer (csPCa), with 46% of men in this group diagnosed with csPCa, compared to just 22% in those with an FTR of ≥0.20. Incorporating the FTR into traditional PSA testing can improve decision-making when recommending biopsies," the researchers reported.

Prostate cancer remains a significant health concern for men, with early detection being crucial for better treatment outcomes. PSA testing measures the amount of PSA in the blood, a protein the prostate gland produces. Elevated PSA levels are often associated with prostate cancer, but they can also be influenced by benign conditions like benign prostatic hyperplasia (BPH) or prostatitis. This can make interpreting PSA levels challenging, particularly when PSA readings fall within the "gray zone" between 1.5 and 4 ng/mL. In this range, PSA levels are neither normal nor high, complicating whether to proceed with a biopsy.

While the prostate-specific antigen (PSA) test has long been used for screening, its accuracy in diagnosing csPCa can be limited, especially in men with PSA levels below 4 ng/mL. Considering this, Dixon T.S. Woon, Department of Urology, Austin Health, Melbourne, Victoria, Australia, and colleagues aimed to examine the association between the PSA free-to-total ratio (FTR) and csPCa with an International Society of Urological Pathology Grade Group ≥2 in men with low PSA levels (≤4 ng/mL).

For this purpose, the researchers used data from the Prostate Cancer Prevention Trial. They included patients with a PSA level of ≤4 ng/mL who underwent a biopsy within one year of this PSA measurement. Logistic regression was applied to assess the relationship between the FTR and csPCa, adjusting for age and PSA.

The study also employed a re-scaled Brier score, which serves as an index of predictive accuracy, along with decision curve analysis to evaluate the clinical utility of the FTR in decision-making.

The study revealed the following findings:

• A total of 406 patients were analyzed, with 34% having clinically significant prostate cancer (csPCa) and 50% having any grade prostate cancer (PCa).
• Among patients with an FTR ≤0.15, 46% had csPCa, compared to 22% for those with an FTR ≥0.20.
• In a regression model, the predicted probability of csPCa for a 60-year-old with a PSA of 3 ng/mL was 61% when the FTR was 0.05, decreasing to 18% when the FTR was 0.30.
• A clear negative relationship was observed between increasing FTR and the probability of csPCa.
• A model incorporating FTR, PSA, and age provided greater net benefit in decision curve analysis and showed superior discrimination and calibration, as indicated by a higher predictive accuracy index.

"In middle-aged men with a PSA level between 1.5 and 4 ng/mL, who are otherwise recommended for biopsy, a low FTR is linked to higher rates of clinically significant prostate cancer. FTR should be used as an additional, easily accessible, and cost-effective test to enhance the prediction of csPCa and support patient counseling," the researchers concluded.

Reference: https://doi.org/10.1111/bju.16597