UNLABELLED: What's known on the subject? and What does the study add? In spite of its low specificity, PSA is the most widely used screening test for prostate cancer (PCa), and is considered the main cause of the stage migration recently observed. The ratio of free to total PSA (%fPSA) has been shown to increase PSA accuracy in cancer detection; however, few screening studies have systematically evaluated its role in cancer detection rates in men with PSA levels <4.0 ng/mL and normal DRE. The present study supports a possible role of %fPSA as an adjunct to screening in men with total PSA 2.5-4.0 ng/mL and normal DRE, with a marked increase in cancer detection rates in a large Brazilian PCa screening study. We believe that %fPSA maybe a useful refinement to biopsy indications in men with low PSA levels. OBJECTIVE: • To evaluate the role of the free to total prostate-specific antigen ratio (%fPSA) in identifying prostate cancer (PCa) in men with a prostate-specific antigen (PSA) level of 2.5-3.9 ng/mL and a normal digital rectal examination (DRE). PATIENTS AND METHODS: • A prospective PCa screening study was conducted, which included 17571 men aged ≥ 45 years, across six Brazilian states, where men were recalled for further evaluation in the case of either a suspicious DRE and/or PSA ≥ 4.0 ng/mL, or PSA 2.5-3.9 ng/mL and %fPSA ≤ 15. • We evaluated the impact of a %fPSA ≤ 15 on cancer detection rates and the clinical and pathological stage of tumours in men with a normal DRE and PSA 2.5-3.9 ng/mL. RESULTS: • When suspicious DRE and/or PSA ≥ 4.0 ng/mL were considered as criteria to prompt further evaluation, the cancer detection rate was 3.1%. When %fPSA ≤ 15 in men with total PSA levels of 2.5-3.9 ng/mL were considered as criteria, the PCa detection rate increased to 3.7%. Considering %fPSA ≤ 15 in men with PSA 2.5-3.9 ng/mL and normal DRE, the positive predictive value of biopsy was 31.1%. • Clinical stage was more favourable among men with PSA 2.5-3.9 ng/mL, normal DRE, and %fPSA ≤ 15 compared with men with normal DRE and PSA ≥ 4.0 ng/mL (P= 0.02). • Among those who underwent radical prostatectomy, pathological stage and the proportion of insignificant tumours were similar between men with PSA 2.5-3.9 ng/mL, normal DRE findings and %fPSA ≤ 15, and men with PSA ≥ 4.0 ng/mL. CONCLUSIONS: • The use of %fPSA ≤ 15 as a biopsy indication in men with normal DRE and PSA 2.5-4.0 ng/mL in a PCa screening programme, increased cancer detection rates. Tumours in this subset of patients had similar pathological characteristics. • Using %fPSA ≤ 15 to indicate biopsy in men with PSA 2.5-3.9 ng/mL is a useful adjunct to PCa screening.
UNLABELLED: What's known on the subject? and What does the study add? In spite of its low specificity, PSA is the most widely used screening test for prostate cancer (PCa), and is considered the main cause of the stage migration recently observed. The ratio of free to total PSA (%fPSA) has been shown to increase PSA accuracy in cancer detection; however, few screening studies have systematically evaluated its role in cancer detection rates in men with PSA levels <4.0 ng/mL and normal DRE. The present study supports a possible role of %fPSA as an adjunct to screening in men with total PSA 2.5-4.0 ng/mL and normal DRE, with a marked increase in cancer detection rates in a large Brazilian PCa screening study. We believe that %fPSA maybe a useful refinement to biopsy indications in men with low PSA levels. OBJECTIVE: • To evaluate the role of the free to total prostate-specific antigen ratio (%fPSA) in identifying prostate cancer (PCa) in men with a prostate-specific antigen (PSA) level of 2.5-3.9 ng/mL and a normal digital rectal examination (DRE). PATIENTS AND METHODS: • A prospective PCa screening study was conducted, which included 17571 men aged ≥ 45 years, across six Brazilian states, where men were recalled for further evaluation in the case of either a suspicious DRE and/or PSA ≥ 4.0 ng/mL, or PSA 2.5-3.9 ng/mL and %fPSA ≤ 15. • We evaluated the impact of a %fPSA ≤ 15 on cancer detection rates and the clinical and pathological stage of tumours in men with a normal DRE and PSA 2.5-3.9 ng/mL. RESULTS: • When suspicious DRE and/or PSA ≥ 4.0 ng/mL were considered as criteria to prompt further evaluation, the cancer detection rate was 3.1%. When %fPSA ≤ 15 in men with total PSA levels of 2.5-3.9 ng/mL were considered as criteria, the PCa detection rate increased to 3.7%. Considering %fPSA ≤ 15 in men with PSA 2.5-3.9 ng/mL and normal DRE, the positive predictive value of biopsy was 31.1%. • Clinical stage was more favourable among men with PSA 2.5-3.9 ng/mL, normal DRE, and %fPSA ≤ 15 compared with men with normal DRE and PSA ≥ 4.0 ng/mL (P= 0.02). • Among those who underwent radical prostatectomy, pathological stage and the proportion of insignificant tumours were similar between men with PSA 2.5-3.9 ng/mL, normal DRE findings and %fPSA ≤ 15, and men with PSA ≥ 4.0 ng/mL. CONCLUSIONS: • The use of %fPSA ≤ 15 as a biopsy indication in men with normal DRE and PSA 2.5-4.0 ng/mL in a PCa screening programme, increased cancer detection rates. Tumours in this subset of patients had similar pathological characteristics. • Using %fPSA ≤ 15 to indicate biopsy in men with PSA 2.5-3.9 ng/mL is a useful adjunct to PCa screening.