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Detection, Diagnosis, and Prognosis of Prostate Cancer

  • Authors: Authors: H. Ballentine Carter, MD; Angelo DeMarzo, MD, PhD; Hans Lilja, MD, PhD
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Target Audience and Goal Statement

This activity is intended for urologists, medical oncologists, radiation oncologists, and other healthcare professionals who treat patients with prostate cancer.

The goal of this activity is to educate physicians regarding the latest research in the diagnosis, treatment, and prevention of prostate cancer.

Upon completion of this activity, participants will be able to:

  1. Describe the controversies surrounding prostate-specific antigen (PSA) measurement in men at risk for prostate cancer.
  2. Identify emerging imaging strategies for the diagnosis of prostate cancer.
  3. Detail the accepted approaches toward staging and grading prostate tumors.
  4. Evaluate emerging factors for risk stratification and outcomes prediction in patients with prostate cancer.


Medscape requires Authors to disclose any relevant financial relationship within the past 12 months with the manufacturer of any product that may relate to the subject matter of the educational activity, whether or not the activity is commercially supported.

Medscape asks Authors to identify, at first mention, investigational products regulated by the US Food and Drug Administration.


  • H. Ballentine Carter, MD

    Professor of Urology and Oncology, Johns Hopkins University School of Medicine; Director, Division of Adult Urology, Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland


    Disclosure: H. Ballentine Carter, MD, has no significant financial interests or relationships to disclose. Dr. Carter may discuss investigational or unlabeled uses of commercial products in this activity.

  • Angelo DeMarzo, MD, PhD

    Associate Professor of Pathology, Oncology, and Urology; Director, Tissue Microarray Core Facility, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland


    Disclosure: Angelo DeMarzo, MD, PhD, has no significant financial interests or relationships to disclose. Dr. DeMarzo may discuss investigational or unlabeled uses of commercial products in this activity.

  • Hans Lilja, MD, PhD

    Attending Research Clinical Chemist, Departments of Clinical Laboratories, Urology, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY


    Disclosure: Hans Lilja, MD, PhD, has disclosed that he has served as a data evaluator for Ferring Pharmaceuticals, as a consultant or advisor to GenSpera, Inc., and on the prostate cancer steering committee for Sanofi-Synthelabo, and is a patent holder for free PSA assay and hK2 assay. Dr. Lilja may discuss investigational or unlabeled uses of commercial products in this activity.

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Detection, Diagnosis, and Prognosis of Prostate Cancer


Establishing the Diagnosis: Imaging Strategies

Imaging is used to aid in the detection of prostate cancer, to help in clinical staging, primarily in patients at high risk for advanced disease.[8] As described above, TRUS is the most frequently used imaging technique in cancer detection. For determining the extent of disease, computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis and abdomen are the most widely used techniques; bone scintigraphy and positron emission tomography (PET) have more limited roles.

CT of the pelvis and abdomen has not demonstrated consistently high specificity, sensitivity, or positive predictive value, although the rates are slightly higher in patients with extraprostatic extension.[65] By contrast, MRI has shown sensitivity rates of around 80% and above, and specificity rates of around 50% in patients with extracapsular extension; lower rates were consistently seen in patients with seminal vesicle invasion.[71,72] In a study that examined 876 patients from three different hospitals, the accuracy of endorectal MRI in predicting extracapsular extension in intermediate-risk patients after radiation therapy was 78%.[73]

Combining MRI with magnetic resonance spectroscopy (MRS), which provides information on tumor metabolism, may increase the accuracy of MRI in assessing the location and stage of prostate cancer. MRS produces an image based on the presence of small quantities of certain biomolecules (ie, citrate, choline, and creatine), the ratios of which change in prostate cancer compared with benign prostate tissue, resulting in a "chemical fingerprint" that can aid in discriminating cancerous from noncancerous tissue.[65] Preliminary data indicate that MRI/MRS has a sensitivity of 46% to 54% and a specificity of 93% to 96% in predicting extracapsular penetration.[74]

Because MRI has shown low sensitivity in detecting lymph node metastases, technologies that incorporate an agent that can help distinguish normal from malignant nodes have been developed. One such strategy involves injection of iron-containing lymphotropic supermagnetic nanoparticles that are ingested by macrophages in lymph nodes and cause magnetic field changes measurable on MRI.[75] Evaluation of the nanoparticles in 80 patients with organ-confined or locally advanced prostate cancer showed a 71.4% accuracy in staging nodal prostate cancer compared with histopathologic staging, which was significantly more sensitive than conventional MRI on both a per-patient (100%) and node-by-node (90.5%) basis.[75] Of note, this method detected metastases as small as 2 mm, which is considerably smaller than is seen with conventional imaging methods. If these results can be replicated in larger studies, this approach may prove useful in determining which patients will require systemic therapy without having to undergo lymph node dissection. The technology, ferumoxtran-10, is under FDA review at this time.

ProstaScint (indium-capromab pendetide; Cytogen Corporation; Princeton, New Jersey) is a radiolabeled monoclonal antibody directed against the glycoprotein prostate-specific membrane antigen (PSMA). Despite numerous studies of the tool in different patient populations, its value as a detection tool is limited to patients with localized disease. In one study of 487 newly diagnosed patients, a positive ProstaScint scan significantly correlated with findings on PSA in those with localized or regionally advanced disease, but not in patients with distant metastases;[76] in patients with biochemical failure following prostatectomy (n = 1225) or radiotherapy (n = 340), the two were weakly correlated in those with local recurrence, but not in those with local or distant metastases. ProstaScint did not correlate with PSA in patients who failed androgen-deprivation therapy regardless of site of disease.[76] In a second study of 255 patients with early biochemical failure (ie, PSA < 4.0 ng/mL) after radical prostatectomy, ProstaScint uptake was noted in over 70% of patients, but only 30% of those had distant metastases.[77]

By contrast, radionuclide bone scintigraphy is most useful in detecting prostate cancer that has metastasized to bone, particularly in men with a Gleason score > 7, clinical stage > T3, and PSA level of > 15-20 ng/mL.[78]

Populations most likely to benefit from PET remain unknown. Using tracers such as [18F] fluoro-2-deoxy-D-glucose (FDG), PET has shown some utility in staging of nodal and metastatic prostate cancer, but is not useful in diagnosis and local staging because tumors tend to grow slowly and are therefore not as active as in some other tumor types. However, by aiding in the evaluation of changes in tumor burden and location of disease during therapy, PET may be useful in prognosis.[79]

Because none of these modalities can accurately detect or predict prostate cancer in all patients, a combination of tools will be needed to help determine appropriate treatment strategies, particularly in patients who are at high risk for developing metastatic disease.