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Prostate Cancer Diagnosis

Signs and symptoms. Prostate cancer rarely demonstrates early symptoms. A nodule may be noticed on a digital rectal exam as tumor volume increases. Symptoms suggest locally advanced or metastatic disease.  With advanced disease, hematuria, obstructive symptoms and bone pain from metastases can be present.  It is less common to diagnosis advanced disease due to sceening with prostate specific antigen (PSA) and digital rectal exams (DRE).  A histological diagnosis is frequently made using prostate needle biospy with transurethral ultrasound guidance.  DRE and PSA are complementary tests and it is recommended that they are used in combination in assessing prostate cancer risk.   

  • Prostate Specific Antigen [PSA] Improves the postive predictive value of DRE for prostate cancer.
    • 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.
      • The interpretation of PSA values should always include age, presence of urinary tract infection, recent diagnositc procedures, any prstate directed treatments.  
    • 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. 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 10-13 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.  For more on staging

References

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  • 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.
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  • 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.
  • Naughton et al, 2000. Naughton CK, Miller DC, et al: A prospective randomized trial comparing 6 versus 12 prostate biopsy cores: impact on cancer detection. J Urol  2000; 164(2):388-392.
  • 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.
  • Schroder et al, 1998. Schroder FH, van der Maas P, Beemsterboer P, et al: Evaluation of the digital rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst  1998; 90(23):1817-1823.
  • 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.