Utility of free to total PSA ratio in the prediction of prostate cancer in patients with intermediate total PSA levels and negative digital rectal examination
Date of Award
Master of Medicine (MMed)
Pathology (East Africa)
Background: Prostate carcinoma is among the top 5 cancers occurring in Kenyan men. Prostate-specific antigen (PSA) is currently the most important biochemical marker for the diagnosis of prostate cancer and its widespread use as a serum tumor marker has revolutionized the management of patients with prostate cancer. The identification of early prostate cancer is vital in the management of especially men who have mild or vague prostatic symptoms. The most basic and important proxy for determining the need for a biopsy in both symptomatic and asymptomatic(screened) patients is the serum prostatic specific antigen (PSA).If a patients PSA level is above 11 ng/ml then there is a high probability of prostate cancer and a biopsy would be recommended. By contrast, of those patients whose PSA level is between 4 and 11 ng/ml (intermediate range) only25-30% are diagnosed with prostate cancer. As such in these instances the specificity of PSA is reduced, resulting in taking many unnecessary biopsies. Consequently several different methods to enhance the sensitivity and specificity of PSA have been proposed. one of these is the determination of Free PSA levels and use of this as a percentage or ratio of Total PSA.
Objective: To determine utility of Free to Total PSA ratio in enhancing differentiation of prostate cancer from benign prostate disease in male patients with intermediate Total PSA levels (4-11ng/ml) and negative digital rectal examination (DRE) in three hospitals in Nairobi,Kenya.
Design: Cross sectional study
Setting:Aga KhanUniversityHospital,NazarethHospital and St.Marys hospital
Subjects: 180 male patients aged 40 years and above attending urology/surgical clinics at three hospitals, found to have age adjusted total PSA values between 4-11ng/ml with negative digital rectal examination (non suspicious for cancer) and in whom either an ultrasound guided biopsy, transurethral resection of the prostate or prostatectomy was performed and histopathology examination carried out.
Results: On histology, 138(77%) of the 180 patients were diagnosed with benign prostate hyperplasia, 18(10%) with High grade intraepithelial neoplasia(HGPIN )and 24(13%) with carcinoma. Analysis of variance (one way) was performed to compare the mean of age, Total PSA, Free PSA and Free to Total PSA ratio in patients with BPH, HGPIN and Carcinoma.
No significant statistical difference in mean age and Total PSA (6.614, 6.781, and 7.6) was found between patients with BPH, HGPIN and Carcinoma respectively.
Mean Free PSA was significantly higher in patients with BPH (1.637) than those with HGPIN (1.012) and prostate carcinoma (0.743). No significant statistical difference was found in the mean Free PSA of patients with HGPIN and those with carcinoma respectively.
Mean Free to Total PSA ratio was significantly higher in patients with BPH (0.259) than those with HGPIN (0.157) and prostate carcinoma (0.121). No significant statistical difference was found in the mean Free to Total PSA of patients with HGPIN and those with carcinoma.The sensitivity, specificity, positive and negative predictive values at various free to total PSA cut offs was determined. Receiver operating characteristic curves for Total, Free and Free to Total PSA were constructed and the area under curve (AUC) and Youden’s index determined.
The AUC for Total, Free and Free to total PSA was 0.584, 0.842 and 0.875 respectively. Free to total PSA showed a significantly higher AUC and therefore a better discriminatory power.A Cut off of 0.19 gave the highest Youdens index. This cut off would give a sensitivity of 83.3%and specificity of 79%.
Conclusion: In this study, the overall ability of Free to Total PSA to discriminate between individuals with carcinoma of prostate from those with benign prostatic disease was shown to be superior to Total PSA. Using a cut off of 0.19 would give the highest sensitivity and specificity.
Kirimi, M. .. (2009). Utility of free to total PSA ratio in the prediction of prostate cancer in patients with intermediate total PSA levels and negative digital rectal examination (Unpublished master's dissertation). .