To compare the clinical usefulness of the serum markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we measured them by radioimmunoassay in 2200 serum samples from 699 patients, 378 of whom had prostatic cancer. PSA was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 patients with unsuspected early disease and all of 115 with more advanced disease. The PSA level increased with advancing clinical stage and was proportional to the estimated volume of the tumor. The PAP concentration was elevated in only 57 of the patients with cancer and correlated less closely with tumor volume. PSA was increased in 86 percent and PAP in 14 percent of the patients with benign prostatic hyperplasia. After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. If initially elevated, PAP fell to normal levels within 24 hours but always remained detectable. In six patients followed postoperatively by means of repeated measurements, PSA--but not PAP--appeared to be useful in detecting residual and early recurrence of tumor and in monitoring responses to radiation therapy. Prostate massage increased the levels of both PSA and PAP approximately 1.5 to 2 times. Needle biopsy and transurethral resection increased both considerably. We conclude that PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.
This article has been cited by other articles:
Wang, G., Wang, J., Sadar, M. D.
(2008). Crosstalk between the Androgen Receptor and {beta}-Catenin in Castrate-Resistant Prostate Cancer. Cancer Res.
68: 9918-9927
[Abstract][Full Text]
Cramer, S. D., Sun, J., Zheng, S. L., Xu, J., Peehl, D. M.
(2008). Association of Prostate-Specific Antigen Promoter Genotype with Clinical and Histopathologic Features of Prostate Cancer. Cancer Epidemiol. Biomarkers Prev.
17: 2451-2457
[Abstract][Full Text]
Bifulco, M., Malfitano, A. M., Pisanti, S., Laezza, C.
(2008). Endocannabinoids in endocrine and related tumours. Endocr Relat Cancer
15: 391-408
[Abstract][Full Text]
Seaton, A., Scullin, P., Maxwell, P. J., Wilson, C., Pettigrew, J., Gallagher, R., O'Sullivan, J. M., Johnston, P. G., Waugh, D. J. J.
(2008). Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis
29: 1148-1156
[Abstract][Full Text]
Loeb, S., Catalona, W. J.
(2008). What to Do with an Abnormal PSA Test. The Oncologist
13: 299-305
[Abstract][Full Text]
Tajiri, M., Ohyama, C., Wada, Y.
(2008). Oligosaccharide Profiles of the Prostate Specific Antigen in Free and Complexed Forms from the Prostate Cancer Patient Serum and in Seminal Plasma: a Glycopeptide Approach. Glycobiology
18: 2-8
[Abstract][Full Text]
Nam, R. K., Toi, A., Klotz, L. H., Trachtenberg, J., Jewett, M. A.S., Appu, S., Loblaw, D. A., Sugar, L., Narod, S. A., Kattan, M. W.
(2007). Assessing Individual Risk for Prostate Cancer. JCO
25: 3582-3588
[Abstract][Full Text]
Thompson, I. M., Ankerst, D. P.
(2007). Prostate-specific antigen in the early detection of prostate cancer. CMAJ
176: 1853-1858
[Abstract][Full Text]
Fall, K., Garmo, H., Andren, O., Bill-Axelson, A., Adolfsson, J., Adami, H.-O., Johansson, J.-E., Holmberg, L.
(2007). Prostate-Specific Antigen Levels as a Predictor of Lethal Prostate Cancer. JNCI J Natl Cancer Inst
99: 526-532
[Abstract][Full Text]
Sommer, F. G., Scardino, P. T., Hricak, H., Kattan, M. W., Wang, L.
(2007). Radiology Research and Rock Soup. Radiology
242: 637-639
[Full Text]
Wachter, S., Tomek, S., Kurtaran, A., Wachter-Gerstner, N., Djavan, B., Becherer, A., Mitterhauser, M., Dobrozemsky, G., Li, S., Potter, R., Dudczak, R., Kletter, K.
(2006). 11C-Acetate Positron Emission Tomography Imaging and Image Fusion With Computed Tomography and Magnetic Resonance Imaging in Patients With Recurrent Prostate Cancer. JCO
24: 2513-2519
[Abstract][Full Text]
Darling, M.R., Jackson-Boeters, L., Daley, T.D., Diamandis, E.P.
(2006). Human Kallikrein 6 Expression in Salivary Gland Tumors. J. Histochem. Cytochem.
54: 337-342
[Abstract][Full Text]
Nanni, S., Priolo, C., Grasselli, A., D'Eletto, M., Merola, R., Moretti, F., Gallucci, M., De Carli, P., Sentinelli, S., Cianciulli, A. M., Mottolese, M., Carlini, P., Arcelli, D., Helmer-Citterich, M., Gaetano, C., Loda, M., Pontecorvi, A., Bacchetti, S., Sacchi, A., Farsetti, A.
(2006). Epithelial-Restricted Gene Profile of Primary Cultures from Human Prostate Tumors: A Molecular Approach to Predict Clinical Behavior of Prostate Cancer. Mol Cancer Res
4: 79-92
[Abstract][Full Text]
Hood, B. L., Darfler, M. M., Guiel, T. G., Furusato, B., Lucas, D. A., Ringeisen, B. R., Sesterhenn, I. A., Conrads, T. P., Veenstra, T. D., Krizman, D. B.
(2005). Proteomic Analysis of Formalin-fixed Prostate Cancer Tissue. Mol. Cell. Proteomics
4: 1741-1753
[Abstract][Full Text]
Huizen, I. V., Wu, G., Moussa, M., Chin, J. L., Fenster, A., Lacefield, J. C., Sakai, H., Greenberg, N. M., Xuan, J. W.
(2005). Establishment of a Serum Tumor Marker for Preclinical Trials of Mouse Prostate Cancer Models. Clin. Cancer Res.
11: 7911-7919
[Abstract][Full Text]
Malik, A., Afaq, F., Sarfaraz, S., Adhami, V. M., Syed, D. N., Mukhtar, H.
(2005). Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc. Natl. Acad. Sci. USA
102: 14813-14818
[Abstract][Full Text]
Nagahara, H., Mimori, K., Utsunomiya, T., Barnard, G. F., Ohira, M., Hirakawa, K., Mori, M.
(2005). Clinicopathologic and Biological Significance of Kallikrein 6 Overexpression in Human Gastric Cancer. Clin. Cancer Res.
11: 6800-6806
[Abstract][Full Text]
Welch, H. G., Schwartz, L. M., Woloshin, S.
(2005). Prostate-Specific Antigen Levels in the United States: Implications of Various Definitions for Abnormal. JNCI J Natl Cancer Inst
97: 1132-1137
[Abstract][Full Text]
Le, L., Chi, K., Tyldesley, S., Flibotte, S., Diamond, D. L., Kuzyk, M. A., Sadar, M. D.
(2005). Identification of Serum Amyloid A as a Biomarker to Distinguish Prostate Cancer Patients with Bone Lesions. Clin. Chem.
51: 695-707
[Abstract][Full Text]
Sarfaraz, S., Afaq, F., Adhami, V. M., Mukhtar, H.
(2005). Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer. Cancer Res.
65: 1635-1641
[Abstract][Full Text]
Stanley, R. J.
(2004). Screening Revisited. Am. J. Roentgenol.
183: 1537-1537
[Full Text]
Ohyama, C., Hosono, M., Nitta, K., Oh-eda, M., Yoshikawa, K., Habuchi, T., Arai, Y., Fukuda, M.
(2004). Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy. Glycobiology
14: 671-679
[Abstract][Full Text]
Lee, H.-H., Ho, C.-T., Lin, J.-K.
(2004). Theaflavin-3,3'-digallate and penta-O-galloyl-{beta}-D-glucose inhibit rat liver microsomal 5{alpha}-reductase activity and the expression of androgen receptor in LNCaP prostate cancer cells. Carcinogenesis
25: 1109-1118
[Abstract][Full Text]
Tricoli, J. V., Schoenfeldt, M., Conley, B. A.
(2004). Detection of Prostate Cancer and Predicting Progression: Current and Future Diagnostic Markers. Clin. Cancer Res.
10: 3943-3953
[Abstract][Full Text]
Adams, K. F., Chen, C., Newton, K. M., Potter, J. D., Lampe, J. W.
(2004). Soy Isoflavones Do Not Modulate Prostate-Specific Antigen Concentrations in Older Men in a Randomized Controlled Trial. Cancer Epidemiol. Biomarkers Prev.
13: 644-648
[Abstract][Full Text]
Kishi, T., Soosaipillai, A., Grass, L., Little, S. P., Johnstone, E. M., Diamandis, E. P.
(2004). Development of an Immunofluorometric Assay and Quantification of Human Kallikrein 7 in Tissue Extracts and Biological Fluids. Clin. Chem.
50: 709-716
[Abstract][Full Text]
Blaszczyk, N., Masri, B. A., Mawji, N. R., Ueda, T., McAlinden, G., Duncan, C. P., Bruchovsky, N., Schweikert, H.-U., Schnabel, D., Jones, E. C., Sadar, M. D.
(2004). Osteoblast-Derived Factors Induce Androgen-Independent Proliferation and Expression of Prostate-Specific Antigen in Human Prostate Cancer Cells. Clin. Cancer Res.
10: 1860-1869
[Abstract][Full Text]
Wu, P., Zhu, L., Stenman, U.-H., Leinonen, J.
(2004). Immunopeptidometric Assay for Enzymatically Active Prostate-Specific Antigen. Clin. Chem.
50: 125-129
[Abstract][Full Text]
Nam, R. K., Zhang, W. W., Trachtenberg, J., Jewett, M. A. S., Emami, M., Vesprini, D., Chu, W., Ho, M., Sweet, J., Evans, A., Toi, A., Pollak, M., Narod, S. A.
(2003). Comprehensive Assessment of Candidate Genes and Serological Markers for the Detection of Prostate Cancer. Cancer Epidemiol. Biomarkers Prev.
12: 1429-1437
[Abstract][Full Text]
Sathya, G., Chang, C.-y., Kazmin, D., Cook, C. E., McDonnell, D. P.
(2003). Pharmacological Uncoupling of Androgen Receptor-mediated Prostate Cancer Cell Proliferation and Prostate-specific Antigen Secretion. Cancer Res.
63: 8029-8036
[Abstract][Full Text]
Bott, S R J, Birtle, A J, Taylor, C J, Kirby, R S
(2003). Prostate cancer management: (1) an update on localised disease. Postgrad. Med. J.
79: 575-580
[Abstract][Full Text]
Thompson, I., Leach, R. J., Pollock, B. H., Naylor, S. L.
(2003). Prostate Cancer and Prostate-Specific Antigen: The More We Know, the Less We Understand. JNCI J Natl Cancer Inst
95: 1027-1028
[Full Text]
Cramer, S. D., Chang, B.-L., Rao, A., Hawkins, G. A., Zheng, S. L., Wade, W. N., Cooke, R. T., Thomas, L. N., Bleecker, E. R., Catalona, W. J., Sterling, D. A., Meyers, D. A., Ohar, J., Xu, J.
(2003). Association Between Genetic Polymorphisms in the Prostate-Specific Antigen Gene Promoter and Serum Prostate-Specific Antigen Levels. JNCI J Natl Cancer Inst
95: 1044-1053
[Abstract][Full Text]
Nam, R. K., Zhang, W. W., Trachtenberg, J., Diamandis, E., Toi, A., Emami, M., Ho, M., Sweet, J., Evans, A., Jewett, M. A.S., Narod, S. A.
(2003). Single Nucleotide Polymorphism of the Human Kallikrein-2 Gene Highly Correlates With Serum Human Kallikrein-2 Levels and in Combination Enhances Prostate Cancer Detection. JCO
21: 2312-2319
[Abstract][Full Text]
Kishi, T., Grass, L., Soosaipillai, A., Scorilas, A., Harbeck, N., Schmalfeldt, B., Dorn, J., Mysliwiec, M., Schmitt, M., Diamandis, E. P.
(2003). Human Kallikrein 8, a Novel Biomarker for Ovarian Carcinoma. Cancer Res.
63: 2771-2774
[Abstract][Full Text]
Khan, M. A., Partin, A. W.
(2003). Management of High-Risk Populations with Locally Advanced Prostate Cancer. The Oncologist
8: 259-269
[Abstract][Full Text]
Balk, S. P., Ko, Y.-J., Bubley, G. J.
(2003). Biology of Prostate-Specific Antigen. JCO
21: 383-391
[Abstract][Full Text]
Zhu, L., Leinonen, J., Zhang, W.-M., Finne, P., Stenman, U.-H.
(2003). Dual-Label Immunoassay for Simultaneous Measurement of Prostate-specific Antigen (PSA)-{alpha}1-Antichymotrypsin Complex Together with Free or Total PSA. Clin. Chem.
49: 97-103
[Abstract][Full Text]
Isono, T., Tanaka, T., Kageyama, S., Yoshiki, T.
(2002). Structural Diversity of Cancer-related and Non-Cancer-related Prostate-specific Antigen. Clin. Chem.
48: 2187-2194
[Abstract][Full Text]
Leinonen, J., Wu, P., Stenman, U.-H.
(2002). Epitope Mapping of Antibodies against Prostate-specific Antigen with Use of Peptide Libraries. Clin. Chem.
48: 2208-2216
[Abstract][Full Text]
Jain, S, Bhojwani, A G, Mellon, J K
(2002). Improving the utility of prostate specific antigen (PSA) in the diagnosis of prostate cancer: the use of PSA derivatives and novel markers. Postgrad. Med. J.
78: 646-650
[Abstract][Full Text]
Grzeda, B. R., Le Bui, T., Warner, C. N., Pirucki, T. L., Dewey, L. M., Babich, M., Maggiore, J. A.
(2002). Measurement of Prostate-specific Antigen by Use of a Novel Blood Collection and Analytical System. Clin. Chem.
48: 1272-1278
[Abstract][Full Text]
Sadar, M. D., Akopian, V. A., Beraldi, E.
(2002). Characterization of a New in Vivo Hollow Fiber Model for the Study of Progression of Prostate Cancer to Androgen Independence. Molecular Cancer Therapeutics
1: 629-637
[Abstract][Full Text]
Djavan, B., Remzi, M., Zlotta, A., Seitz, C., Snow, P., Marberger, M.
(2002). Novel Artificial Neural Network for Early Detection of Prostate Cancer. JCO
20: 921-929
[Abstract][Full Text]
Chang, C.-Y., Walther, P. J., McDonnell, D. P.
(2001). Glucocorticoids Manifest Androgenic Activity in a Cell Line Derived from a Metastatic Prostate Cancer. Cancer Res.
61: 8712-8717
[Abstract][Full Text]
Yousef, G. M., Diamandis, E. P.
(2001). The New Human Tissue Kallikrein Gene Family: Structure, Function, and Association to Disease. Endocr. Rev.
22: 184-204
[Abstract][Full Text]
Stamey, T. A.
(2001). Preoperative Serum Prostate-specific Antigen (PSA) Below 10 {micro}g/L Predicts Neither the Presence of Prostate Cancer Nor the Rate of Postoperative PSA Failure. Clin. Chem.
47: 631-634
[Abstract][Full Text]
Xing, N., Chen, Y., Mitchell, S. H., Young, C. Y.F.
(2001). Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis
22: 409-414
[Abstract][Full Text]
Martenson, E. D., Hansson, L.O., Nilsson, B., von Schoultz, E., Brahme, E. M., Ringborg, U., Hansson, J.
(2001). Serum S-100B Protein as a Prognostic Marker in Malignant Cutaneous Melanoma. JCO
19: 824-831
[Abstract][Full Text]
Peter, J., Unverzagt, C., Krogh, T. N., Vorm, O., Hoesel, W.
(2001). Identification of Precursor Forms of Free Prostate-specific Antigen in Serum of Prostate Cancer Patients by Immunosorption and Mass Spectrometry. Cancer Res.
61: 957-962
[Abstract][Full Text]
Kattan, M. W., Zelefsky, M. J., Kupelian, P. A., Scardino, P. T., Fuks, Z., Leibel, S. A.
(2000). Pretreatment Nomogram for Predicting the Outcome of Three-Dimensional Conformal Radiotherapy in Prostate Cancer. JCO
18: 3352-3359
[Abstract][Full Text]
Koller-Strametz, J., Fritzer, M., Gwechenberger, M., Geppert, A., Heinz, G., Haumer, M., Koreny, M., Maurer, G., Siostrzonek, P.
(2000). Elevation of Prostate-Specific Markers After Cardiopulmonary Resuscitation. Circulation
102: 290-293
[Abstract][Full Text]
Diamandis, E. P.
(2000). Prostate-specific Antigen: A Cancer Fighter and a Valuable Messenger?. Clin. Chem.
46: 896-900
[Abstract][Full Text]
Gripp, S., Haller, J. C., Metz, J., Willers, R.
(2000). Prostate-Specific Antigen: Effect of Pelvic Irradiation. Radiology
215: 757-760
[Abstract][Full Text]
Grande, M., Carlström, K., Rozell, B. L., Stege, R., Pousette, A.
(2000). Prognostic Value of Serial Tissue Prostate-specific Antigen Measurements during Different Hormonal Treatments in Prostate Cancer Patients. Clin. Cancer Res.
6: 1790-1795
[Abstract][Full Text]
Peter, J., Unverzagt, C., Hoesel, W.
(2000). Analysis of Free Prostate-specific Antigen (PSA) after Chemical Release from the Complex with {alpha}1-Antichymotrypsin (PSA-ACT). Clin. Chem.
46: 474-482
[Abstract][Full Text]
Prakash, S., Robbins, P. W.
(2000). Glycotyping of prostate specific antigen. Glycobiology
10: 173-176
[Abstract][Full Text]
Tanaka, T., Isono, T., Yoshiki, T., Yuasa, T., Okada, Y.
(2000). A Novel Form of Prostate-specific Antigen Transcript Produced by Alternative Splicing. Cancer Res.
60: 56-59
[Abstract][Full Text]
Latham, J. P. F., Searle, P. F., Mautner, V., James, N. D.
(2000). Prostate-specific Antigen Promoter/Enhancer Driven Gene Therapy for Prostate Cancer: Construction and Testing of a Tissue-specific Adenovirus Vector. Cancer Res.
60: 334-341
[Abstract][Full Text]
Stege, R., Grande, M., Carlström, K., Tribukait, B., Pousette, A.
(2000). Prognostic Significance of Tissue Prostate-specific Antigen in Endocrine-treated Prostate Carcinomas. Clin. Cancer Res.
6: 160-165
[Abstract][Full Text]
Sutkowski, D. M., Goode, R. L., Baniel, J., Teater, C., Cohen, P., McNulty, A. M., Hsiung, H. M., Becker, G. W., Neubauer, B. L.
(1999). Growth Regulation of Prostatic Stromal Cells by Prostate-Specific Antigen. JNCI J Natl Cancer Inst
91: 1663-1669
[Abstract][Full Text]
Jhaveri, F. M., Klein, E. A., Kupelian, P. A., Zippe, C., Levin, H. S.
(1999). Declining Rates of Extracapsular Extension After Radical Prostatectomy: Evidence for Continued Stage Migration. JCO
17: 3167-3172
[Abstract][Full Text]
Virtanen, A., Gomari, M., Kranse, R.
(1999). Estimation of Prostate Cancer Probability by Logistic Regression: Free and Total Prostate-specific Antigen, Digital Rectal Examination, and Heredity Are Significant Variables. Clin. Chem.
45: 987-994
[Abstract][Full Text]
Zhang, W.-M., Finne, P., Leinonen, J., Vesalainen, S., Nordling, S., Stenman, U.-H.
(1999). Measurement of the Complex between Prostate-specific Antigen and {alpha}1-Protease Inhibitor in Serum. Clin. Chem.
45: 814-821
[Abstract][Full Text]
Michel, S., Deleage, G., Charrier, J.-P., Passagot, J., Battail-Poirot, N., Sibai, G., Jolivet, M., Jolivet-Reynaud, C.
(1999). Anti-Free Prostate-specific Antigen Monoclonal Antibody Epitopes Defined by Mimotopes and Molecular Modeling. Clin. Chem.
45: 638-650
[Abstract][Full Text]
Zhang, W.-M., Finne, P., Leinonen, J., Vesalainen, S., Nordling, S., Rannikko, S., Stenman, U.-H.
(1998). Characterization and immunological determination of the complex between prostate-specific antigen and {alpha}2-macroglobulin. Clin. Chem.
44: 2471-2479
[Abstract][Full Text]
Allard, W. J., Zhou, Z., Yeung, K. K.
(1998). Novel immunoassay for the measurement of complexed prostate-specific antigen in serum. Clin. Chem.
44: 1216-1223
[Abstract][Full Text]
Iczkowski, K. A., Bostwick, D. G., Catalona, W. J., Smith, D. S., Foucar, E., Pitts, Jr, W. R., McNaughton Collins, M., Barry, M. J., Ransohoff, D. F.
(1998). Detection of Early Prostate Cancer: Serendipitous or Systematic?. JAMA
279: 1439-1441
[Full Text]
Robinson, L. A., Preksto, D., Muro-Cacho, C., Hubbell, D. S.
(1998). Intraoperative Gamma Probe-Directed Biopsy of Asymptomatic Suspected Bone Metastases. Ann. Thorac. Surg.
65: 1426-1432
[Abstract][Full Text]
Guise, T. A., Mundy, G. R.
(1998). Cancer and Bone. Endocr. Rev.
19: 18-54
[Abstract][Full Text]
Takayama, T. K., Fujikawa, K., Davie, E. W.
(1997). Characterization of the Precursor of Prostate-specific Antigen. ACTIVATION BY TRYPSIN AND BY HUMAN GLANDULAR KALLIKREIN. J. Biol. Chem.
272: 21582-21588
[Abstract][Full Text]
Chen, S.-F., Xu, Y., Ip, M. P.-C.
(1997). Electrochemical Enzyme Immunoassay for Serum Prostate-Specific Antigen at Low Concentrations. Clin. Chem.
43: 1459-1461
[Full Text]
Wei, C., Willis, R. A., Tilton, B. R., Looney, R. J., Lord, E. M., Barth, R. K., Frelinger, J. G.
(1997). Tissue-specific expression of the human prostate-specific antigen gene in transgenic mice: Implications for tolerance and immunotherapy. Proc. Natl. Acad. Sci. USA
94: 6369-6374
[Abstract][Full Text]
Herrala, A., Kurkela, R., Porvari, K., Isomaki, R., Henttu, P., Vihko, P.
(1997). Human prostate-specific glandular kallikrein is expressed as an active and an inactive protein. Clin. Chem.
43: 279-284
[Abstract][Full Text]
Qian, Y., Sensibar, J. A., Zelner, D. J., Schaeffer, A. J., Finlay, J. A., Rittenhouse, H. G., Lee, C.
(1997). Two-dimensional gel electrophoresis detects prostate-specific antigen–{alpha}1-antichymotrypsin complex in serum but not in prostatic fluid. Clin. Chem.
43: 352-359
[Abstract][Full Text]
Morgan, T. O., Jacobsen, S. J., McCarthy, W. F., Jacobson, D. J., McLeod, D. G., Moul, J. W.
(1996). Age-Specific Reference Ranges for Serum Prostate-Specific Antigen in Black Men. NEJM
335: 304-310
[Abstract][Full Text]
Dearnaley, D P
(1994). Current Issues in Cancer: Cancer of the prostate. BMJ
308: 780-784
[Full Text]
(1987). PROSTATE-SPECIFIC ANTIGEN: A USEFUL TUMOR MARKER. JWatch General
1987: 3-3
[Full Text]