• Signs and symptoms. Prostate cancer demonstrates few early symptoms. A nodule may be noticed on a digital rectal exam as tumor volume increases. With advanced disease, hematuria, obstructive symptoms and bone pain from metastases can be present.
• Prostate Specific Antigen [PSA]
  • Biochemical characteristics.
    • PSA is a 240 amino acid single chain glycoprotein that has a molecular weight of 34 kd. It is coded on chromosome 19 (6 Kb: 4 introns, 5 exons), is homologous to members of the kallikrein gene superfamily, and is designated human kallikrein3 (hK3). It behaves as a serine protease.
  • Physiology.
    • PSA liquefies the seminal coagulum that is formed after ejaculation.
    • A substrate produced in the seminal vesicles has been identified. PSA has chymotrypsinand trypsin-like activity. Its half-life is 2.2 to 3.2 days.
  • Marker Properties
    • The generally used monoclonal assay (2 murine MAbs for two specific epitopes) suggest a normal serum value of 4.0 ng/mL. Serum values are not generally altered by DRE, but can be affected by urologic instrumentation, ejaculation, and prostate biopsy. Benign conditions that can raise PSA levels include prostatitis, prostate infarction, and benign prostatic hypertrophy.
  • Cancer detection (see screening)
  • Treatment surveillance. Serum levels monitored after surgery and external beam radiation therapy. Surgical failure clearly defined by PSA level >0.4 ng/ml. Radiation failure currently defined by 3 successive rises in PSA over time. Several biases built into this definition.
• Transrectal Ultrasound. Limited role in diagnosis. Primarily used for appropriate needle placement during biopsy. Classic finding of hypoechoic lesion has a 30% chance of being prostate cancer
• Prostate needle biopsy. Spring loaded gun obtains 10-12 cores of tissue from the gland under ultrasound guidance. Parameters such a percent positive cores can provide predictive information on treatment outcome. Procedure is well tolerated. Major side effect is hematospermia
• Bone Scan. In patients with a PSA <10.0ng/ml the chance of a positive scan is approximately 1:1000. May be used as a baseline study. 30-50 of bone mass must be replaced for it to be positive. Plain fim correlates or CT/MRI are use to resolve questionable findings
• CT and body coil MRI have no proven contemporary role in the staging of prostate cancer. Endorectal coil may provide additional staging resolution in patients with PSA values between 10 and 20 who have >50% of biopsy cores positive for cancer.
• Bilateral pelvic lymph node dissection. Provides staging information in patients with high grade/stage disease with elevated serum PSA. Generally part of radical prostatectomy. Given stage shift in disease, frozen section less often employed in most cases. Can be performed laparoscopically as a separate procedure.
• Multimodal staging. Multiple clinical factors can be analyzed for contribution prediction of pathologic stage or clinical outcome. Multivariable analysis, continuous nomograms, and neural networks can be employed.

References

• Albertson PC, Hanley JA, Gleason DR, Barry MJ: Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 280:975-980, 1998.
• Cooney, K. A., J. D. McCarthy, et al. (1997). "Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study." J Natl Cancer Inst 89(13): 955-9.
• Devgan, S. A., B. E. Henderson, et al. (1997). "Genetic variation of 3 beta-hydroxysteroid dehydrogenase type II in three racial/ethnic groups: implications for prostate cancer risk." Prostate 33(1): 9-12.
• Greenlee, R. T., T. Murray, et al. (2000). "Cancer statistics, 2000." CA Cancer J Clin 50(1): 7-33.
• Jemal, A., T. Murray, et al. (2003). "Cancer statistics, 2003." CA Cancer J Clin 53(1): 5-26.
• Kalapurakal, J. A., A. N. Jacob, et al. (1999). "Racial differences in prostate cancer related to loss of heterozygosity on chromosome 8p12-23." Int J Radiat Oncol Biol Phys 45(4): 835-40.
• Makridakis, N., R. K. Ross, et al. (1997). "A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase." Cancer Res 57(6): 1020-2.
• Makridakis, N. M., R. K. Ross, et al. (1999). "Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA." Lancet 354(9183): 975-8.
• Pettaway, C. A., P. Troncoso, et al. (1998). "Prostate specific antigen and pathological features of prostate cancer in black and white patients: a comparative study based on radical prostatectomy specimens." J Urol 160(2): 437-42.
• Platz, E. A., M. N. Pollak, et al. (1999). "Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men." Cancer Epidemiol Biomarkers Prev 8(12): 1107-10.
• Ross, R. K., L. Bernstein, et al. (1992). "5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males." Lancet 339(8798): 887-9.
• Sakr, W. A., D. J. Grignon, et al. (1995). "Epidemiology of high grade prostatic intraepithelial neoplasia." Pathol Res Pract 191(9): 838-41.
• Smith, J. R., D. Freije, et al. (1996). "Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search." Science 274(5291): 1371-4.
• Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004 May 27;350(22):2239-46.
• Tricoli, J. V., D. L. Winter, et al. (1999). "Racial differences in insulin-like growth factor binding protein-3 in men at increased risk of prostate cancer." Urology 54(1): 178-82.
• Winter, D. L., A. L. Hanlon, et al. (2001). "Plasma levels of IGF-1, IGF-2, and IGFBP-3 in white and African-American men at increased risk of prostate cancer." Urology 58(4): 614-8.
• Xu, J., D. Meyers, et al. (1998). "Evidence for a prostate cancer susceptibility locus on the X chromosome." Nat Genet 20(2): 175-9.

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