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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.

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  • 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


Emerging Detection Techniques

Much research is currently dedicated to addressing the need in prostate cancer diagnosis to reliably distinguish between malignancy and benign conditions, such as BPH, and to distinguish between clinically significant and insignificant cancers. PSA has not yet proven consistent in this arena.

Over the last several years, there has been a large number of exciting discoveries regarding the molecular biology of prostate cancer that are expected to lead to greater availability of tools for molecular diagnostics and the development of improved detection methods in various settings, including assessment of cancer risk, disease staging, predicting response to therapy, disease recurrence and/or metastasis, and prognosis. Although a comprehensive list is beyond the scope of this report, Table 3 illustrates a few of the well-studied and/or most promising molecular markers under investigation and their potential applications.

Unfortunately, clinical application of many of these markers is lacking. Most have not been tested in well-designed prospective studies, and there remains a great need for further studies using patients derived from diverse populations in order to determine which biomarkers may be applied in the clinical setting. These studies typically require large groups of patients that cannot be accrued at a single institution. Several research networks, including two funded through the National Institutes of Health, namely the Early Detection Research Network (EDRN) and the Prostate Specialized Projects of Research Excellence (SPORE), are beginning to address these issues on a more national scale.

Table 3. Disease Markers and Detection Techniques Under Investigation

Marker Comments
PSA subfractions: complexed PSA, free PSA, proPSA, intact PSA, benign PSA Absolute concentrations in serum and percentage relative to total PSA may help discriminate between malignancy and benign conditions.[10]
Insulin-like growth factor (IGF-1), insulin-like growth factor binding protein (IGFBP-3) High serum IGF-1 concentrations associated with increased risk for prostate cancer[37,38]
Prostate-specific membrane antigen (PSMA) Can be detected in tissue with ProstaScint; serum concentrations elevated in prostate cancer; discriminates between cancer and BPH or no disease; also being investigated as a therapeutic target[39]
Human kallikrein 2 (hK2) Shares 80% of amino acid sequence with PSA and is produced in prostatic epithelium at concentrations 50-100x less than PSA.[40] Generally elevated in prostate cancer vs BPH,[41] and is more sensitive than PSA at detecting extracapsular extension.[42,43]
Gene- or Cell-Based Biomarkers
Glutathione S-transferase-pi (GSTP1) Protects cells from oxidative damage; reduced expression in prostate cancer due to hypermethylation of its promoter region; distinguishes between BPH and cancer; methylation status of GSTP1 gene promoter quantified in prostatic tissue, cells derived from serum, urine, and seminal plasma via PCR[39,44,45]
Telomerase activity Telomerase activity is detectable in the vast majority of prostate cancers but not in benign prostate tissues.[46] Improved methods of telomerase detection may make this marker useful for early detection of prostate cancer in tissue samples or in urine.
PTEN A lipid phosphatase that functions as a tumor suppressor by inhibiting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Gene somatically deleted or mutated in some prostate cancers. Protein can be detected by IHC and decreased levels are associated with higher grade and stage.[45,47,48]
CDKN1B (P27) Cyclin-dependent kinase inhibitor. Protein decreased in prostate tumor cells and levels correlate with worse outcome.[45,49]
Ki-67 Marker of cellular proliferation. Fractions of cells staining positive by IHC associated with worse outcome.[50-52]
Chromosome 8p22 loss and 8q24 (C-MYC) gain 8q24 overrepresentation, especially in combination with loss of 8q22 using a FISH assay, is associated with prostate cancer progression in men with stage pT2N0M0, pT3N0M0, and pT2-3N1-3M0 prostate cancers[53]
Prostate stem cell antigen (PSCA) Cell surface protein found primarily in the prostate; increased expression in many higher-grade prostate cancers and most metastatic lesions; correlates with late-stage disease; detection in prostatic tissue via FISH, PCR, IHC[39]
Alpha-methylacyl-CoA racemase (AMACR) Mitochondrial and peroxisomal enzyme involved in oxidation; overexpressed in prostate cancer; detected in tissue by IHC, and in conjunction with loss of basal cell markers (eg, basal cytokeratins, p63), can help establish diagnosis of cancer on prostate needle biopsy.[54] Assays to detect a humoral response may supplement PSA screening in identifying significant tumors.[55]

Prostate cancer risk is also influenced by hereditary factors. Although no specific genetic tests are yet available, the relatively new field of molecular epidemiology is beginning to reveal that inheriting certain gene variants (alleles) of various different types of genes may influence prostate cancer risk[45,56,57] and eventually help determine which patients should be more diligently screened with PSA testing.