Prostate Cancer – A Stealthy Disease
By Steven H. Barag, DO, FACOFP
ABSTRACT: Other than non-melanoma skin cancer, prostate cancer is the most common cancer in men in the United States (except for non-melanoma skin cancer). The clinical behavior of prostate cancer ranges from a microscopic well-differentiated tumor of little clinical importance to an aggressive cancer with substantial invasive and metastatic potential.1 Prostate cancer has been detected with increasing frequency due in part to the widespread availability of serum prostate specific antigen (PSA) testing. Incidence is higher in blacks than in whites in the United States.
The manner in which prostate cancer is diagnosed today is different from that of the pre-PSA era. In the past, prostate cancer was first detected by digital rectal examination (DRE) or because of urinary symptoms.2 Today, prostate cancer is usually detected commonly by an elevated serum PSA, greater than 4.5 units.3
While symmetric enlargement and firmness of the prostate on digital rectal exam is most typical of benign prostatic hyperplasia (BPH), asymptomatic areas of induration or frank nodules are suggestive of prostate cancer.4 Symptomatic prostate cancer can cause urinary urgency, nocturia, frequency and hesitancy. These symptoms are also present in men with BPH and are most likely caused by BPH rather than cancer.
New onset erectile dysfunction should always raise suspicion for prostate gland pathology since an enlarging gland may encroach upon periprostatic tissue, where the neurovascular bundle is located, thereby affecting erectile function. Hematuria and hematospermia are uncommon presentations of prostate cancer5, but their presence in older men should prompt its consideration in the differential diagnosis. A small percentage of men present with symptoms of metastatic disease (example, bone pain or rarely spinal cord compression).6
Clinical Presentation
A 58-year-old African American male from Nigeria presented a history of renal calculi and benign prostate hyperplasia since at least 2004. In January 2005, a urology consult for urgency and renal calculi was recommended. Prostate size at that time was grade 1, smooth, firm and mobile. In September 2005, PSA examination was 0.1 ng/mL.
In December 2005 in response to low back discomfort, a lumbar spine x-ray was performed, which showed degenerative spurring, stable since August 2004 and small bilateral renal calculi.
In September 2006, PSA was again 0.1 ng/mL. The patient had again seen the Urologist for renal calculi.
In December 2006, the patient had another episode of renal lithiasis. In January 2007, CT scan revealed prostatic enlargement.
In March 2007, a prostate biopsy was recommended by the Urologist. In June 2007 the biopsy was completed.
In July 2007, CT scan of the pelvis without contrast revealed metastatic disease in the pelvis and iliac chain lymph nodes were involved, prostate hypertrophy and urinary bladder calculi were also present. Lumbar spine x-rays revealed degenerative spondylosis without focal lytic or neoplastic lesions. Pelvic x-rays showed left inferior ramus metastasis. Radionuclide whole body bone scan revealed diffuse osseous metastatic disease.
In January 2007 an Oncology assessment identified adenoocarcinoma of the right side of the prostate involving 80 percent of the specimen and Gleason 7 with perineal invasion. The Oncology assessment also found left prostate adenocarcinoma involving 90 percent of the specimen and Gleason 9 with extensive perineal invasion.7
This case punctuates the false sense of security physicians can have by unconditionally relying on any test. This 58-year-old male had metastatic prostate cancer to pelvic lymph nodes, the pelvis, ribs and vertebrae without elevation of PSA, and no change in PSA velocity.
Completing the Diagnostic
and Staging Evaluation
If a prostate biopsy specimen is interpreted as containing carcinoma, an additional evaluation of clinical staging is required to determine the extent or spread. The primary goal of the staging evaluation is to rule out the presence of disease outside of the prostate gland and to assess the likelihood of finding potential resectable organ-confined disease.8
The tumor-node-metastases or TNM system is the most popular method of staging prostate cancer.9
The definition of the T stage:
Analysis of tumor histology (Gleason grade) provides some index of prognosis and may also guide local therapy. With the Gleason histological scoring system, tumors are graded from one to five based upon the degree of glandular differentiation and structural architecture. Grade one represents the most well-differentiated appearance, and grade five represents these that are the most poorly-differentiated.
A primary and secondary score are reported and combined to form the combined Gleason score. As an example, if a biopsy consists predominantly of grade three and secondarily grade four disease, the combined score is three plus four or seven.
Clinical staging provides the major means of determining prognosis and selecting therapy.
A positive radionuclide bone scan indicates extraprostatic spread and eliminates the potential for curative surgery. The yield of bone scans in men with serum PSA values of less than 10 ng/mL is extremely low.10 The combination of Gleason grade, serum PSA concentration and clinical stage may be particularly useful to predict the likelihood of a positive bone scan.
Although a CT scan of the abdomen and pelvis is often recommended as part of the staging evaluation for newly diagnosed prostate cancer, the inability of CT scans to diagnose extraprostatic extension and seminal vesicle invasion accurately is well known. Most staging CT scans are negative for metastasis.
Diagnosis
The diagnosis of prostate cancer is most often suspected after finding an elevated serum PSA.11 Less commonly, a diagnostic evaluation is instituted due to abnormal findings on digital rectal examination. Prostate biopsy is the gold standard for prostate cancer diagnosis.12
Serum PSA Elevation
Although serum PSA is a prostate specific marker, elevations can be caused by both cancer and benign conditions such as BPH. Malignant prostate tissue generates more PSA than normal or hypoplastic tissue, probably because of the increased cellularity associated with cancer. Moreover, cancerous tissue may disrupt the prostate-blood barrier, further increasing the serum concentration of PSA. There is a significant overlap of the serum PSA values that accompany prostate cancer and BPH, particularly in the four to 10 ng/mL range.13 The likelihood of finding cancer on a prostate biopsy increases with higher PSA values.
Prostate biopsy is uniformly recommended in men whose serum PSA is greater than 10 ng/mL since the chance of finding prostate cancer is greater than 50 percent.
The management of men with lesser PSA elevations is less clear since the majority will have negative biopsies. However, a substantial number of men with prostate cancer have a serum PSA concentration below 4 ng/mL. Twenty-one percent of cancers diagnosed for reasons other than an elevated PSA had a serum PSA level between 2.6 and 3.9 ng/mL.14
The prevalence of high grade cancers, Gleason score of 7 or higher was 12.5 percent of all cancers associated with a PSA level of 0.5 ng/mL or less as compared to 25 percent of those associated with a PSA level of 3.1 to 4 ng/mL or more.14
Even if the serum PSA is in the normal range (for example, less than 4 ng/mL), prostate biopsy may be indicated in men with a digital rectal examination suspicious for cancer. As many as 43 percent of patients with prostate cancer have normal serum PSA values.15
Transrectal ultrasonography (TRUS) may be used to evaluate abnormalities detected by digital rectal exam. Transrectal biopsy is a relatively simple office technique usually performed without sedation or analgesia.
The location of the biopsy is often determined by findings on digital rectal exam or ultrasonography. However, in many men, these tests are normal and the diagnosis of prostate cancer may be made by blind biopsies.
Because prostate cancer is often multifocal and the sampled volume is small with a standard needle biopsy, repeat evaluations may be appropriate in the face of a persistent suspicion of prostate cancer if the initial biopsies are negative.
Clinical Presentation Follow Up
Oncological evaluation revealed the need for chemotherapy for metastatic disease using Taxotere plus carboplatin plus prednisone. Additionally, radiation therapy, bisphosphonate with Zometa was started and monthly Lupron injections were required. Casodex will be initiated pending radiation therapy.
Conclusion
As with all areas of medical investigation, prostate cancer is far from completely understood. Close medical supervision by the primary care physician and specialty consultants will hopefully reveal a good outcome for this patient.
Dr. Barag is a 1973 graduate of the University of Health Sciences in Kansas City, Missouri. He received his certification in family medicine in 1985 and re-certification in 1995. He has served as chair of the family practice department with distinction at two hospitals – Pomona Valley Hospital Medical Center and San Antonio Community Hospital. Currently he practices family medicine at his Rancho Cucamonga Multi-Specialty Medical Center.
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Non-cited References