Determination of an optimum cut-off point for %fPSA/tPSA to improve detection of prostate cancer
Keywords:
Prostate Specific Antigen, Prostatic neoplasms, ROC curve, Prostatic HyperplasiaAbstract
Background: Total serum prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) are known to be useful in the detection of prostate carcinoma (PCa). It has been reported that %fPSA/tPSA is more accurate when it comes to distinguishing PCa from non-malignant conditions such as BPH. The recommended cut-off value of %fPSA/tPSA in western countries is 20-25%. Through this study, we aim to determine an optimum cut-off value for %fPSA/tPSA in an Indian population.
Methods: This study was performed at our institution between September 2015 and August 2016. The study population included 181 patients who had prostate enlargement and who then underwent PSA based prostate cancer screening with tPSA and %fPSA/tPSA and whose diagnosis was later confirmed by histopathology. An ROC curve analysis was performed to determine sensitivity, specificity and other performance characteristics. The optimum cut-off value of %fPSA/tPSA was determined from ROC curve using Youden’s index.
Result: Malignant histology was seen in 17 (9.4%) cases. ROC curve analysis of %fPSA/tPSA revealed an AUC value of 0.777. The cut-off value of %fPSA/tPSA having the optimum balance between sensitivity and specificity was found to be 12.07% (Sensitivity: 70.6%, Specificity: 84.8%, Positive predictive value: 0.324, Negative predictive value: 0.965, Positive likelihood ratio: 4.631 and Negative likelihood ratio: 0.347).
Conclusion: The cut-off value of %fPSA/tPSA obtained from our study (12.07%), which was conducted on a South Indian population, is different from the cut-off values seen in western countries and in many studies conducted in western populations.
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DOI:Â 10.21276/APALM.1254
References
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2. Dalva I, Akan H, Yildiz O, Telli C, Bingol N. The clinical value of the ratio of free prostate specific antigen to total prostate specific antigen. Int Urol Nephrol. 1999;31:675-80.
3. Carter HB. Prostate cancers in men with low PSA levels--must we find them? N Engl J Med. 2004;350:2292
4. Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res. 1991;51:222-6.
5. Amirrasouli H, Kazerouni F, Sanadizade M, Sanadizade J, Kamalian N, Jalali M et al. Accurate cut-off point for free to total prostate-specific antigen ratio used to improve differentiation of prostate cancer from benign prostate hyperplasia in Iranian population. Urol J. 2010;7(2):99-104.
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7. Catalona WJ, Smith DS, Wolfert RL, Wang TJ, Rittenhouse HG, Ratliff TL, et al. Evaluation of percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening. J Am Med Assoc 1995; 274:1214e20.
8. Catalona WJ, Partin Aw, Slawin KM, 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.
9. Ito K, Yamamoto T, Ohi M, Kurokawa K, Suzuki K, Yamanaka H. Free/total PSA ratio is a powerful predictor of future prostate cancer morbidity in men with initial PSA levels of 4.1 to 10.0 ng/mL. Urology. 2003;61:760-4.
10. Polascik TJ, Oesterling JE, Partin AW. Prostate specific antigen: a decade of discovery—what we have learned and where we are going. J. Urol. 1999;162: 293–306.
11. Lilja H, Oldbring J, Rannevik G, Laurell CB. Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen, J. Clin. Invest. 1987;80:281–285.
12. Stenman UH, Prostate-specific antigen, clinical use and staging: an overview. Br. J. Urol. 1997:79(Suppl.1):53–60.
13. Aus G, Damber JE, Khatami A, Lilja H, Stranne J, Hugosson J. Individualized screening interval for prostate cancer based on prostate-specific antigen level: results of a prospective, randomized, population-based study. Arch. Intern. Med. 2005;165:1857–1861.
14. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL et al. Prevalence of prostate cancer among men with a prostate-specific antigen level b or =4.0 ng per milliliter, N. Engl. J. Med. 2004;350:2239–2246.
15. Christensson A, Bjork T, Nilsson O, et al. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol. 1993;150:100-5.
16. Catalona wJ, Smith DS, Ratliff TL, Basler Jw. Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. Jama. 1993;270:948-54.
17. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of percentage of free prostate specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter trial. J Am Med Assoc 1998;279:1542e7.
18. van Cangh PJ, De Nayer P, De Vischer L, Sauvage P, Tombal B, Lorge F, et al. Free to total prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia (BPH) in the diagnostic gray zone of 1.8 to 10 ng/mL total PSA. Urology 1996;48:67e70.
19. Catalona WJ, Partin AW, Slawin KM, Naughton CK, Brawer MK, Flanigan RC, et al. Percentage of free PSA in black versus white men for detection and staging of prostate cancer: a prospective multicenter clinical trial. Urology 2000;55:372e6.
20. Safarinejad MR. Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Iran. Ann Oncol. 2006 Jul;17(7):1166-71.
21. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millenium. Urology 2001;58:843e8.
22. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of percentage of free prostate specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter trial. J Am Med Assoc 1998;279:1542e7.
23. Chun FK, Perrotte P, Briganti A, Benayoun S, Lebeau T, Ramirez A, et al. Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer. BJUI 2006;98:50e3.
24. Suzuki H, Komiya A, Kamiya N, Takashi I, Koji K, Junichiro M, et al. Development of a nomogram to predict probability of positive initial prostate biopsy among Japanese patients. Urology 2006;67:131e5.
25. Prcic A, Begic E, Hiros M. Actual Contribution of Free to Total PSA Ratio in Prostate Diseases Differentiation. Med Arch. 2016;70(4):288-292.
26. Yilmaz H, Ciftci S, Yavuz U, Ustuner M, Saribacak A, Dillioglugil O. Percentage of free prostate-specific antigen (PSA) is a useful method in deciding to perform prostate biopsy with higher core numbers in patients with low PSA cut-off values. Kaohsiung J Med Sci. 2015;31(6):315-9
27. Pourmand G, Ramezani R, Sabahgoulian B, Nadali F, Mehrsai AR, Nikoobakht,MR et al. Preventing Unnecessary Invasive Cancer-Diagnostic Tests: Changing the Cut-off Points.Iran J Public Health. 2012; 41(2): 47–52.
28. Dalva I, Akan H, Yildiz O, Telli C, Bingol N. The clinical value of the ratio of free prostate specific antigen to total prostate specific antigen. Int Urol Nephrol. 1999;31:675-8.
29. Thakur V, Talwar M, Singh P. Low free to total PSA ratio is not a good discriminator of chronic prostatitis and prostate cancer: An Indian experience. Indian Journal of Cancer. 2014;51(3):335.
2. Dalva I, Akan H, Yildiz O, Telli C, Bingol N. The clinical value of the ratio of free prostate specific antigen to total prostate specific antigen. Int Urol Nephrol. 1999;31:675-80.
3. Carter HB. Prostate cancers in men with low PSA levels--must we find them? N Engl J Med. 2004;350:2292
4. Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res. 1991;51:222-6.
5. Amirrasouli H, Kazerouni F, Sanadizade M, Sanadizade J, Kamalian N, Jalali M et al. Accurate cut-off point for free to total prostate-specific antigen ratio used to improve differentiation of prostate cancer from benign prostate hyperplasia in Iranian population. Urol J. 2010;7(2):99-104.
6. Luderer AA, Chen YT, Soriano TF, Kram WJ, Carlson G, Cuny C, et al. Measurement of the proportion of free to total prostate specific antigen improves diagnostic performance of prostate specific antigen in the diagnostic gray zone of total prostate specific antigen. Urology 1995;46:187e94.
7. Catalona WJ, Smith DS, Wolfert RL, Wang TJ, Rittenhouse HG, Ratliff TL, et al. Evaluation of percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening. J Am Med Assoc 1995; 274:1214e20.
8. Catalona WJ, Partin Aw, Slawin KM, 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.
9. Ito K, Yamamoto T, Ohi M, Kurokawa K, Suzuki K, Yamanaka H. Free/total PSA ratio is a powerful predictor of future prostate cancer morbidity in men with initial PSA levels of 4.1 to 10.0 ng/mL. Urology. 2003;61:760-4.
10. Polascik TJ, Oesterling JE, Partin AW. Prostate specific antigen: a decade of discovery—what we have learned and where we are going. J. Urol. 1999;162: 293–306.
11. Lilja H, Oldbring J, Rannevik G, Laurell CB. Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen, J. Clin. Invest. 1987;80:281–285.
12. Stenman UH, Prostate-specific antigen, clinical use and staging: an overview. Br. J. Urol. 1997:79(Suppl.1):53–60.
13. Aus G, Damber JE, Khatami A, Lilja H, Stranne J, Hugosson J. Individualized screening interval for prostate cancer based on prostate-specific antigen level: results of a prospective, randomized, population-based study. Arch. Intern. Med. 2005;165:1857–1861.
14. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL et al. Prevalence of prostate cancer among men with a prostate-specific antigen level b or =4.0 ng per milliliter, N. Engl. J. Med. 2004;350:2239–2246.
15. Christensson A, Bjork T, Nilsson O, et al. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol. 1993;150:100-5.
16. Catalona wJ, Smith DS, Ratliff TL, Basler Jw. Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. Jama. 1993;270:948-54.
17. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of percentage of free prostate specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter trial. J Am Med Assoc 1998;279:1542e7.
18. van Cangh PJ, De Nayer P, De Vischer L, Sauvage P, Tombal B, Lorge F, et al. Free to total prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia (BPH) in the diagnostic gray zone of 1.8 to 10 ng/mL total PSA. Urology 1996;48:67e70.
19. Catalona WJ, Partin AW, Slawin KM, Naughton CK, Brawer MK, Flanigan RC, et al. Percentage of free PSA in black versus white men for detection and staging of prostate cancer: a prospective multicenter clinical trial. Urology 2000;55:372e6.
20. Safarinejad MR. Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Iran. Ann Oncol. 2006 Jul;17(7):1166-71.
21. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millenium. Urology 2001;58:843e8.
22. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al. Use of percentage of free prostate specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter trial. J Am Med Assoc 1998;279:1542e7.
23. Chun FK, Perrotte P, Briganti A, Benayoun S, Lebeau T, Ramirez A, et al. Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer. BJUI 2006;98:50e3.
24. Suzuki H, Komiya A, Kamiya N, Takashi I, Koji K, Junichiro M, et al. Development of a nomogram to predict probability of positive initial prostate biopsy among Japanese patients. Urology 2006;67:131e5.
25. Prcic A, Begic E, Hiros M. Actual Contribution of Free to Total PSA Ratio in Prostate Diseases Differentiation. Med Arch. 2016;70(4):288-292.
26. Yilmaz H, Ciftci S, Yavuz U, Ustuner M, Saribacak A, Dillioglugil O. Percentage of free prostate-specific antigen (PSA) is a useful method in deciding to perform prostate biopsy with higher core numbers in patients with low PSA cut-off values. Kaohsiung J Med Sci. 2015;31(6):315-9
27. Pourmand G, Ramezani R, Sabahgoulian B, Nadali F, Mehrsai AR, Nikoobakht,MR et al. Preventing Unnecessary Invasive Cancer-Diagnostic Tests: Changing the Cut-off Points.Iran J Public Health. 2012; 41(2): 47–52.
28. Dalva I, Akan H, Yildiz O, Telli C, Bingol N. The clinical value of the ratio of free prostate specific antigen to total prostate specific antigen. Int Urol Nephrol. 1999;31:675-8.
29. Thakur V, Talwar M, Singh P. Low free to total PSA ratio is not a good discriminator of chronic prostatitis and prostate cancer: An Indian experience. Indian Journal of Cancer. 2014;51(3):335.
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01-09-2017
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Nair VG, Shariff MH. Determination of an optimum cut-off point for %fPSA/tPSA to improve detection of prostate cancer. Ann of Pathol and Lab Med [Internet]. 2017 Sep. 1 [cited 2024 Nov. 19];4(4):A428-432. Available from: https://pacificejournals.com/journal/index.php/apalm/article/view/apalm1254
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