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.
Advantages and disadvantages of interstitial brachytherapy
Advantages. Interstitial brachytherapy is done as a single outpatient procedure. It can deliver a targeted high dose of radiation. And it is associated with a lower rate of posttreatment incontinence than radical prostatectomy, and a lower cost.
Disadvantages. There are limited data to support long-term cancer control in intermediate- and high-risk disease. Short-term adverse effects include dysuria, hematuria, urinary urgency, and urinary frequency in up to 80% of patients.29 Voiding symptoms typically peak 1 to 3 months after the procedure and subside after 8 to 12 months. Erectile dysfunction has been reported in 30% to 35% of men at 5 years after the procedure. Other possible adverse effects include urethral stricture, incontinence, recurrent hematuria, rectal bleeding, proctitis, and the development of bladder cancer and other secondary cancers.
EXTERNAL BEAM RADIOTHERAPY
In external beam radiotherapy, radiation is delivered to the prostate and surrounding tissues via an external energy source. Electrons, protons, or neutrons are used, and although each has theoretical advantages over the others, all appear to have similar clinical efficacy.
As with brachytherapy, the object—and the challenge—is to deliver an effective dose of radiation to the tumor while sparing adjacent organs. Intensity-modulated delivery is a radiotherapy technique that delivers more of the radiation dose where we want it to go—and less where we don’t want it to go. For prostate cancer, the target dose with intensity-modulated delivery is typically 75 to 85 Gy, in doses of 2 to 2.25 Gy for 30 to 36 days.
Androgen deprivation therapy before or after external beam radiotherapy augments the effects of the radiotherapy, particularly in patients with high-risk disease.30
The oncologic efficacy of intensity-modulated radiotherapy in patients at low and intermediate risk appears commensurate with that of radical prostatectomy. In one study,31 in low-risk cases, biochemical disease-free survival rates were 85% for radiotherapy vs 93% for prostatectomy; in intermediate-risk cases, 82% for radiotherapy and 87% for prostatectomy; and in high-risk cases, 62% for combined androgen deprivation and radiotherapy vs 38% for prostatectomy.31
Advantages and disadvantages of external beam radiotherapy
Advantages. External beam radiotherapy is noninvasive. It can treat the prostate as well as areas outside the prostate in patients with intermediate- and high-risk disease, and it is proven effective for high-risk cancer when used in combination with androgen deprivation.
Disadvantages. On the other hand, radiotherapy requires a series of daily treatments, which can be inconvenient and burdensome to the patient. Its adverse effects are similar to those of brachytherapy, and it is expensive. Long-term adverse effects include irritative voiding symptoms (frequency, urgency, nocturia), hemorrhagic cystitis, bowel symptoms (pain with defecation, tenesmus, bleeding), and a significantly higher lifetime risk of a secondary malignancy, particularly of the bladder and rectum.32
External beam radiotherapy also induces tissue changes in the pelvis that make salvage surgery more difficult. Patients in whom radiotherapy is ineffective as monotherapy and who require salvage prostatectomy typically have poor outcomes in terms of disease control, continence, and potency.
COMBINED RADIATION THERAPY: BETTER, OR OVERTREATMENT?
Many patients are offered a combination of external beam radiotherapy and interstitial brachytherapy. The rationale is that the combination can boost the dose of radiation to the prostate and at the same time treat cancer that has extended beyond the prostate or to the pelvic lymph nodes.
The radiation dose in the combined approach is 45 to 50 Gy (vs 70 to 80 Gy in monotherapy), thereby minimizing toxicity.
This combination has not been shown to improve overall survival or cancer-specific survival compared with either therapy alone, and it likely constitutes overtreatment.33 Adverse effects of combination therapy include erectile dysfunction, rectal and bladder toxicity, and secondary malignancy.
A serious complication associated more often with the combination of external beam radiotherapy and brachytherapy than other treatments is rectoprostatic fistula, a condition that requires complex reconstructive surgery and often requires permanent urinary and fecal diversion.34
CRYOTHERAPY: MORE STUDY NEEDED
Refinements in cryoablative therapy to destroy prostate tissue have improved the safety and efficacy of this procedure significantly over the past decade. The AUA consensus guidelines recognize cryotherapy as a viable primary cancer monotherapy, but it is most commonly used as a salvage therapy after failure of radiation therapy.
The procedure involves ultrasonographically guided stereotactic placement of cryoprobes into the prostate via a transperineal approach. Argon is pumped through the probes under pressure to initiate ice formation, and repeated freeze-thaw cycles cause tissue damage and necrosis.
Rates of biochemical recurrence at 5 years in patients at low, intermediate, and high risk have been reported at 16%, 27%, and 25%, respectively.35 The presence of viable cancer on biopsy specimens after primary cryoablation has been reported at 15%, compared with 25% after definitive radiation therapy.35
Advantages and disadvantages of cryotherapy
Cryotherapy can destroy cancer tissue in a minimally invasive way. It has no long-term delayed adverse effects, and it is a low-cost and convenient outpatient procedure.
On the other hand, we lack long-term data on its oncologic efficacy, acute complications, and late adverse effects. Acute complications occur in up to 16% of patients and include acute urinary retention requiring prolonged catheterization, hematuria, urethral sloughing, perineal pain, and incontinence.36 Potential late effects include rectoprostatic fistula (< 1%), incontinence (< 5%), persistent hematuria, and chronic pelvic pain.36
Cryoablation therapy appears to have a more significant negative impact on sexual function than does brachytherapy.37
More study of the complications and efficacy of cryotherapy is needed before the procedure can be adopted as routine primary monotherapy.
