Free PSA in men with clinical BPH has limited value, "Beyond the Abstract," by Anil Mandhani

BERKELEY, CA (UroToday.com) - There is significant geographical variation in the incidence of prostate cancer, with the lowest rates reported from Asian countries.[1] In most countries PSA cut-off is still taken as 4ng/ml for biopsy, with varied detection rate. Free PSA has been described to aid in reducing unnecessary biopsies when the total PSA is between 4-10ng/ml.[2] Data on free PSA characteristics have been derived from population based screening mostly on asymptomatic men, but rationale for its pervasive use in men presenting with lower urinary tract symptoms ( LUTS) is not understood.

In a prospective setup, 170 men of 50 to 75 years of age presenting to a urology office with LUTS, normal rectal examination (RE), and raised PSA between 4-20ng/ml had their free PSA levels tested. Due to lower incidence and positive predictive value of total PSA in Indian men, free PSA was done in the PSA range of 4-20mg/ml.

Of those 170 men, 40 (24.7%) had cancer on biopsy. The mean age was 67.5 ± 6.7 years. The median value of f/t PSA for men with cancer was 5.6% (1-25%), and 9.4% (1-63%) for those without cancer. The specificity of f/t PSA ratio at cut off levels 7%, 10%, and 15% was 73%, 60%, 45% for PSA range of 4-10ng/ml and 63%, 47%, and 35% for PSA range of 4-20ng/ml PSA. Area under the curve with f/t PSA ratio for predicting prostate cancer was 0.63 (confidence interval [CI]: 0.54-0.71) P value 0.010 in PSA levels of 4-20 ng/ml and 0.71 (CI: 0.59-0.82) P value 0.004 in the PSA range between 4 and 10 ng/ml.

The possible reason for low specificity could be that symptomatic men have relatively higher total PSA levels (which is a denominator) due to a greater component of benign prostate tissue and have subclinical inflammation of the prostate.[3] Hence, overall f/t PSA ratio becomes lower than that of asymptomatic men without cancer.[3]

This study found a very limited value of free PSA to improve specificity of total PSA in symptomatic men. There is a significant overlap of f/t PSA ratio in men with cancer and BPH. In places where symptomatic men are screened for prostate cancer, the use of “free PSA” should be reconsidered.[4]

References:

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61:69-90.
  2. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: A prospective multicenter clinical trial. JAMA 1998; 279:1542-7.
  3. Jung K, Meyer A, Lein M, Rudolph B, Schnorr D, Loening SA. Ratio of free-to-total prostate specific antigen in serum cannot distinguish patients with prostate cancer from those with chronic inflammation of the prostate. J Urol 1998; 159:1595-8.
  4. Agnihotri S, Mittal RD, Ahmad S, Mandhani A. Free to total serum prostate specific antigen ratio in symptomatic men does not help in differentiating benign from malignant disease of the prostate. Indian J Urol 2014;30:28-32.

Written by:
Anil Mandhani as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Free to total serum prostate specific antigen ratio in symptomatic men does not help in differentiating benign from malignant disease of the prostate - Abstract

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