A practical guide to prostate cancer diagnosis and management
ABSTRACTScreening, diagnosis, and management of prostate cancer can be complicated, with no clear consensus about key issues. We present our approach, which reflects the guidelines of the American Urological Association (AUA).
KEY POINTS
- The AUA recommends annual screening with both digital rectal examination (DRE) and prostate-specific antigen (PSA) testing starting at age 40 for all men whose life expectancy is more than 10 years. Guidelines from other organizations differ somewhat.
- If the DRE is abnormal or if the PSA level is persistently higher than 2.5 μg/L, then biopsy should be considered.
- In low-risk cases, active surveillance may be acceptable in lieu of immediate treatment. Patient education, accurate disease assessment, and compliance with monitoring are critical considerations.
- The most common primary treatments are active surveillance, prostatectomy, interstitial brachytherapy, external beam radiotherapy, and cryotherapy. Newer ablative and focal therapies may offer an advantage in select patients. Which treatment to use is highly patient-dependent.
- Single-institution, single-surgeon reports and advertisements tend to underestimate rates of impotence after prostatectomy, and as a result patients may have false expectations.
HIGH-INTENSITY FOCUSED ULTRASOUND: NOT YET FDA-APPROVED
High-intensity focused ultrasound (HIFU) is not yet approved by the US Food and Drug Administration (other than in an approved research protocol) but is used in Canada and in certain countries of Europe and Asia. It involves the insertion of a transducer into the rectum that generates a high-intensity, focused beam that heats target tissue in the prostate to a high temperature. This temperature triggers a heat-shock response that leads to cellular apoptosis and tissue necrosis. The procedure can be done with or without magnetic resonance imaging (MRI) guidance.
Biochemical recurrence rates at 2 years after the procedure have been reported between 23% and 50%, but long-term efficacy data are lacking.38,39
Advantages and disadvantages of ultrasound
HIFU is a minimally invasive, low-cost, outpatient procedure that offers trackless delivery of energy to the prostate: ie, there is no direct mechanical penetration into the tissue.
Complications include rectal-wall injury, fistula, acute urinary retention, hematuria, and urethral stricture.
FOCAL ABLATION: GETTING ATTENTION, BUT STILL UNDER DEVELOPMENT
Focal ablation for prostate cancer has been receiving much attention. This treatment uses heat energy to destroy tumor cells, guided by high-resolution endorectal-coil MRI. The procedure is in the developmental stages and is available only in research protocols.
The procedure has several major hurdles to overcome before becoming acceptable for clinical practice. First, prostate cancer is multifocal, and microscopic tumor foci are likely present that are invisible even to MRI, so ablation of only part of the prostate leaves the rest of the gland at risk of continued or de novo tumor growth.
Second, a wide range of sensitivities and specificities have been reported for endorectal coil MRI for detecting prostate cancer: its sensitivity has ranged from 27% to 100%, and its specificity has ranged from 32% to 99%.40
ANDROGEN DEPRIVATION, AN ADJUVANT THERAPY
Androgen deprivation therapy (medical castration) is not effective as a monotherapy for prostate cancer. A large population-based study in men with localized prostate cancer showed no higher rate of overall survival at 10 years with primary androgen deprivation therapy than with conservative management.41
Androgen deprivation is achieved with a leutinizing hormone-releasing hormone agonist such as leuprolide (Lupron) or goserelin (Zoladex), or an antiandrogen drug such as flutamide or bicalutamide (Casodex), or a combination of each.
Adverse effects include hot flashes, gynecomastia, decreased libido, erectile dysfunction, weight gain, and hyperlipidemia. Long-term effects include osteoporosis and a significantly higher risk of cardiac events, new-onset type 2 diabetes mellitus, and stroke.
Currently, the only recognized role for androgen deprivation therapy in prostate cancer is as an adjunct to external beam radiotherapy or as a treatment of metastatic prostate cancer.
Orchiectomy
The other way to eliminate testicular production of testosterone is surgical castration. Bilateral orchiectomy has advantages over medical androgen deprivation therapy in that it costs less, is highly reliable, and is done as a single treatment on an outpatient basis. Disadvantages include surgery-related morbidity and the irreversible nature of the procedure. The adverse effects are similar to those of androgen deprivation therapy.
POSTTREATMENT MONITORING
The management of patients with recurrent prostate cancer can be complex, and these patients should be referred to a medical or urologic oncologist.42,43
Often, a rise in PSA after primary therapy represents a regrowth of cancer; 30% to 60% of patients with a recurrence have metastasis, and nearly 20% will die from the disease. The average time from documentation of biochemical recurrence to metastatic progression is 8 years. The average time from metastatic progression to death is 5 years.44,45
After radical prostatectomy, the PSA level should be checked every 6 to 12 months for the first 2 years, then annually until the patient’s life expectancy is only 10 years even without prostate cancer. PSA should reach undetectable levels within 4 to 6 weeks after surgery. Biochemical recurrence after surgery is defined as a PSA level of 0.2 μg/L or higher in two serial studies.
After radiation therapy or cryotherapy, monitoring is complicated by the presence of viable prostatic epithelium that continues to produce PSA. During the first 1 to 2 years after radiation therapy, a PSA “bounce” phenomenon is observed whereby PSA levels rise or fluctuate significantly. This bounce should not be mistaken for a recurrence of cancer. The most widely accepted definition of biochemical recurrence is based on the American Society for Therapeutic Radiology and Oncology “Phoenix” criteria, defined as the nadir PSA level plus 2.0 μg/L.46
