eMedicine Specialties > Urology > Cancer, Prostate

Prostate Cancer - Metastatic and Advanced Disease: Differential Diagnoses & Workup

Author: Martha K Terris, MD, FACS, Professor, Department of Surgery, Medical College of Georgia
Coauthor(s): Audrey Rhee, MD, Resident, Department of Urology, Medical College of Georgia; Shaukat M Qureshi, MBBS, FACS, Consulting Staff in Urology, Department of Surgery, Memorial Hospital of Salem County; Clinical Instructor, Department of Urology, Thomas Jefferson University Hospital
Contributor Information and Disclosures

Updated: Jun 4, 2009

Differential Diagnoses

Other Problems to Be Considered

In most cases, the differential diagnoses of advanced prostate cancer do not present any difficulty; however, certain caveats must be considered, as follows:

  • Radiologic findings of bony metastases can mimic Paget disease of the bone. Although bony metastases are blastic in nature, lytic lesions can occur, resulting in pathologic fractures. Osteoporotic fractures due to prolonged luteinizing hormone-releasing hormone (LHRH) therapy must be distinguished from pathologic fractures.
  • Neurological manifestations should be underscored, and elderly patients with a history of prostate cancer who present to the emergency department with sudden onset of weakness of the legs should raise the suspicion of spinal cord compression, necessitating emergency treatment (spinal cord decompression).
  • Similarly, although brain metastases with associated neurological manifestations are rare, they do occur with enough frequency to deserve recognition.
  • Lymphomas can manifest as pelvic masses and bone lesions. Coexistence of lymphomas with prostate cancer has also been reported.
  • Transitional cell carcinoma and sarcoma of the prostate are more common in men who have undergone prior pelvic radiotherapy for prostate cancer than in men who have not. Likewise, squamous cell carcinoma of the prostate may be observed in men treated with hormonal therapy. All of these can present as a large pelvic mass with or without metastases.

Workup

Laboratory Studies

  • Hematological workup should include a CBC count and a chemistry profile, including serum creatinine, liver function tests, serum PSA, free-to-total PSA ratio, and acid and alkaline phosphatase. Any demonstration of abnormalities by these tests may warrant additional studies.
  • Urinalysis should be performed. If results are abnormal, ie, indicating the presence of an infection, urinalysis should be followed by a urine culture, especially if the patient is symptomatic.
  • Certain molecular markers, such as E-cadherin, p53 and p21, DNA ploidy analysis, human kallikrein 2, and microvessel density (histologic marker of tumor angiogenesis) are also being evaluated to help characterize disease progression.
  • Note that not all patients with a relatively high-grade prostate cancer have elevated PSA levels, nor do elevated PSA levels always signify disease progression.

Imaging Studies

  • Bone scan: At initial presentation with prostate cancer, the value of a bone scan is limited in patients with a Gleason score of less than 7 and a PSA level of less than 20 ng/mL. Those with a Gleason grade of greater than 6 may be candidates for a bone scan, irrespective of their PSA level. A bone scan may be performed as a baseline for treatment response in patients with recurrent metastatic disease at high risk of having bony metastatic disease. Regardless of these guidelines, a bone scan is indicated in patients with prostate cancer who have symptoms suggesting bony metastases. Activity in the bone scan may not be observed until 5 years after micrometastasis has occurred; therefore, negative bone scan results do not rule out metastasis. In biochemical failure, a follow-up bone scan usually has no value until the PSA level exceeds 30 ng/mL.
  • Chest radiography can be used as a baseline study or to help reveal rare pulmonary metastases in select cases.
  • Abdominal or pelvic CT scanning or MRI may reveal extracapsular extension, seminal vesical involvement, pelvic lymph node enlargement, liver metastases, and hydronephrosis (due to result of distal ureteral obstruction) in patients suspected to have locally advanced disease. Because the PSA level does not always correlate with disease progression, repeat CT scans or MRIs can help determine treatment response.
  • ProstaScint scan: Immunoscintigraphy is used to reveal extraprostatic disease (ie, localized recurrence or lymphatic spread). ProstaScint scans frequently yield false-negative results, but the specificity of the study may be improved when combined with single-photon emission CT (SPECT) imaging or CT scanning.

Procedures

  • Transrectal ultrasound-guided needle biopsy of the prostate is indicated for tissue diagnosis in patients who present with elevated PSA levels or abnormal digital rectal examination findings. It should be repeated, if indicated, to determine local recurrence. (For related information, see the article Techniques of Local Anesthesia for Prostate Procedures and Biopsies in eMedicine’s Urology volume.)

Histologic Findings

The Gleason grading system is the most common classification used today that helps determine the histological characteristics of prostate cancer. A grade of 1-5 is assigned to the glandular architecture of the tumor. The sum of the most predominant grade and the second most common histologic pattern determines the Gleason score. Patients with a Gleason score of 6 or higher are likely to progress to advanced cancer (if they have not already done so), as are patients with a PSA value of 10 ng/mL or higher.

Staging

The Whitmore-Jewett classification of stages A-D is no longer widely used. Prostate cancer does not necessarily progress in a sequential manner.

  • Currently, the accepted international tumor, node, metastasis (TNM) staging system pertaining to prostate cancer includes the extent of local disease (T), status of regional lymph nodes (N), and distant metastasis (M).
    • Stage T1-2c - Organ-confined disease
    • Stage T3a - Extracapsular extension of the tumor
    • Stage T3b - Invasion of the seminal vesicle(s)
    • Stage T4 - Tumor fixed or tumor invading adjacent structures other than seminal vesicles (eg, bladder neck, external sphincter, rectum, levator muscles, and/or pelvic floor)
    • Stage NX - Regional lymph nodes cannot be assessed
    • Stage N0 - No regional lymph node metastasis
    • Stage N1 - Regional lymph node(s) metastasis
    • Stage MX - Distant metastasis cannot be assessed.
    • Stage M0 - No distant metastasis
    • Stage M1 - Distant metastasis
    • Stage M1a - Distant metastasis other than regional lymph nodes
    • Stage M1b - Metastasis to bone(s)
    • Stage M1c - Other site(s)
    • Stage pM1c - Metastasis to more than 1 site
  • The definition of stage D by Whitmore-Jewett has been further stratified by Crawford and Blumenstein.3 The additional stratification is thought to improve classification and understanding of a subset of patients who have hormone-insensitive prostate cancer. The staging is as follows:
    • Stage D1 - Involvement of pelvic lymph nodes
    • Stage D1.5 - Rising PSA level after failure of local therapy (ie, biochemical failure)
    • Stage D2 - Metastatic disease to bone and other organs
    • Stage D2.5 - Rising PSA after nadir level
    • Stage D3 - Hormone-refractory prostate cancer
    • Stage D3.5 - Sensitive to hormones
    • Stage D4 - Insensitive to hormones

More on Prostate Cancer - Metastatic and Advanced Disease

Overview: Prostate Cancer - Metastatic and Advanced Disease
Differential Diagnoses & Workup: Prostate Cancer - Metastatic and Advanced Disease
Treatment & Medication: Prostate Cancer - Metastatic and Advanced Disease
Follow-up: Prostate Cancer - Metastatic and Advanced Disease
References
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Further Reading

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Keywords

advanced prostate cancer, metastatic prostate cancer, prostate-specific antigen, PSA, Gleason score, prostatic cancer, combined androgen blockade, CAB, biochemical failure, hormone-refractory prostate cancer, HRPC, luteinizing hormone-releasing hormone, LHRH, androgenic suppression, antiandrogens, orchiectomy

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Contributor Information and Disclosures

Author

Martha K Terris, MD, FACS, Professor, Department of Surgery, Medical College of Georgia
Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Urological Association, New York Academy of Sciences, and Society of University Urologists
Disclosure: Nothing to disclose.

Coauthor(s)

Audrey Rhee, MD, Resident, Department of Urology, Medical College of Georgia
Disclosure: Nothing to disclose.

Shaukat M Qureshi, MBBS, FACS, Consulting Staff in Urology, Department of Surgery, Memorial Hospital of Salem County; Clinical Instructor, Department of Urology, Thomas Jefferson University Hospital
Shaukat M Qureshi, MBBS, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, and Medical Society of New Jersey
Disclosure: Nothing to disclose.

Medical Editor

Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Martin I Resnick, MD †, Former Lester Persky Professor and Chair, Department of Urology, Former Professor, Department of Oncology, Case Western Reserve University School of Medicine
Martin I Resnick, MD † is a member of the following medical societies: American College of Surgeons, American Federation for Medical Research, American Institute of Ultrasound in Medicine, American Medical Association, American Society for Bone and Mineral Research, American Society for Reproductive Medicine, American Society of Andrology, American Surgical Association, American Urological Association, Association for Academic Surgery, Endocrine Society, National Kidney Foundation, Ohio Urological Society, and Pan American Medical Association
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center
Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, and Tennessee Medical Association
Disclosure: Lilly Consulting fee Consulting; Astellas Consulting fee Speaking and teaching; Indevus Consulting fee Speaking and teaching

 
 
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