Radiotherapy For Prostate Cancer: A Review
By Ibrahim Abdalla, MD
The management of newly diagnosed prostate cancer (PC) is usually tailored for each individual patient based on tumor-related prognostic factors (the PSA level, Gleason score (GS), and clinical stage (CS), the number of positive cores, the percentage of cancer in each positive core, and perineural invasion) as well as patient-related factors (age, performance status, and comorbidities). Based on these factors, PC patients are usually stratified into favorable group (PSA<10, GS<7, CS20, GS>8, CS≥T3), and intermediate group (any other patient with factors that do not meet the previous two groups).
For patients with localized PC, curative treatment options include surgery and radiotherapy (external beam, brachytherapy or both). There is no clear cut evidence for the superiority of one option over the others. The recent American Urologic Association (AUA) and National Comprehensive Cancer Network (NCCN) guidelines confirm the well established data of comparable cure rate with any of these curative options. The difference is in the treatment induced side effects - both acute (bleeding, infection, DVT, etc.) and late (urinary incontinence, impotence, rectal and/or bladder damage, urethral stricture).
For patients with more advanced, non-metastatic PC, numerous studies have demonstrated the advantage of androgen blockade (i.e. hormone therapy) and radiotherapy (RT). This combination is now considered by many as the standard of care.
Adjuvant radiation therapy is indicated after surgery to improve cancer control for patients with T3 disease (extracapsular penetration and/or seminal vesicle involvement) or positive surgical margins. RT is also used to salvage late disease recurrence after surgery.
There are two main types of radiotherapy: external beam radiation and brachytherapy. When carefully used by an experienced, well-trained radiation oncology team, both types are outstanding methods of treating PC.
External beam radiation therapy (EBRT)
Patients are treated five days per week over a period of eight to nine weeks. Each treatment lasts only a few minutes and is painless. Prior to treatment, simulation and planning is carefully done using advanced software and imaging to accurately target the prostate and spare the normal surrounding structures (rectum and bladder). Patients are immobilized by a body cast to keep the same position. Radiation beams are custom-shaped and aimed at the prostate from several directions, which makes it less likely to damage normal tissues.
There have been significant improvements in EBRT over the past decade which helps us deliver a higher radiation dose more accurately to the prostate and reduce radiation damage to tissues near the prostate, hence cure more patients and maintain excellent quality of life. Long-term results of RT dose-escalation studies support the use of high dose RT.
Three-dimensional conformal radiation therapy (3D-CRT): Prior to IMRT (see below) 3D-CRT was the standard of care in the 1990s. It is still used to treat patients with prostate cancer when encompassing the pelvic lymph nodes in the RT fields is indicated. Pelvic RT in prostate cancer is controversial at this point but most experts recommend it for unfavorable PC patients.
Intensity modulated radiation therapy (IMRT): IMRT is an advanced form of 3D therapy. It uses a computer-driven machine that actually moves around the patient as it delivers radiation. In addition to shaping the beams and aiming them at the prostate from several angles, the intensity (strength) of the beams can be adjusted to minimize even further the dose reaching the most sensitive normal tissues (rectum, bladder, penile bulb). This allows us to deliver an even higher dose to the cancer areas. Many major hospitals and cancer centers are now able to provide IMRT. RapidArc and Tomotherapy are a modified form of IMRT. Using real-time image-guidance (x-ray or cone beam CT scan) on a daily basis has significantly improved the precision and the accuracy of IMRT. Image-guided IMRT is now considered the state-of-the-art treatment for PC.
Proton beam radiation therapy: Proton beam therapy is related to 3D-CRT and uses a similar approach. But instead of using photons, this technique focuses proton beams on the cancer. Unlike photons, which release energy both before and after they hit their target, protons deposit a very small RT dose in tissues they pass through and then release most of their energy (Bragg peak) at the target. This means that proton beam radiation may be able to deliver more radiation to the prostate and do less damage to nearby normal tissues. As for now, there is no evidence to suggest that proton therapy is more effective or safer than IMRT, and since proton therapy machines cost 10-100 times more than IMRT machines, there are only a handful of them in use in the United States. Currently, no facilities in this region offer this type of treatment. Proton beam radiation may not be covered by all insurance companies at this time.
Brachytherapy (seed implantation or interstitial radiation therapy) is generally used as the sole curative treatment for patients with favorable PC. It is also used in conjunction with hormones and/or external beam RT for the more advanced PC cases (GS>8, PSA>20).
Prior to the seed placement, meticulous planning is done to reach the optimal plan (the total number of seeds, their strength and distribution) to maximize cure and minimize side effects. The radioactive seeds are placed inside thin needles which are inserted through the perineum and into the prostate with ultrasound and fluoroscopy guidance. The most commonly used isotopes are iodine-125 or palladium-103.
Seed implant may not be appropriate for men who have had a transurethral resection of the prostate (TURP), or those who already have severe urinary problems (AUA score>15) since the risk of urinary side effects may be higher. Brachytherapy may not be as effective in men with large prostate glands (>60 cc) because many more seeds may be needed. For patients with favorable PC but have large prostate glands, a short course of hormone therapy beforehand to shrink the prostate usually makes the seed implant feasible and successful.
There is another type of brachytherapy called temporary high dose-rate brachytherapy (HDR) which is used far less commonly than seed implant. In this technique, 12 to 18 catheters are placed through the perineum into the prostate. Radioactive iridium-192 is then placed in the catheters for five to 15 minutes. Generally, about three to four brief treatments are given at least six hours apart, and the radioactive substance is removed each time. The treatments are usually given over a couple of days during which patients are kept in the hospital in supine position. After the last treatment the catheters are removed.
These treatments are usually combined with external beam radiation given at a lower dose than if used by itself. There is no evidence that HDR is better than the other treatment options. Because HDR is usually combined with EBRT and patients must be kept in a supine position for at least two days and are not allowed to sit up or stand up, this technique is not as popular among patients.
Although we are able to deliver much higher doses of radiation than previous generations of radiotherapy, the advancing radiation technology (for external beam or brachytherapy) is associated with much less complications than the previous techniques. The risk of serious complication, such as bowel or bladder perforation or massive bleeding, is less than one percent.
GI: Occasional mild diarrhea, rectal discomfort and hemorrhoid flare may occur. These problems are easily controlled by diet adjustment and rare use of Imodium or similar medications. Most of these problems go away within a month or two after treatments.
GU: Mild dysurea, urinary frequency and urgency do occur. Most do not require any therapy. Flomax does help patients with more severe GU symptoms. These symptoms usually resolve within 2-4 weeks after RT. After brachytherapy, most patients experience moderate to severe urinary obstructive symptoms for about two months after the seed implant, secondary to the prostate gland edema induced by the trauma of needle insertion and subsequently due to radiation dose build up. About one-third of patients require a Foley catheter for 4-5 days after the seed placement.
Other acute side effects: Some fatigue and mild skin irritation.
Impotence: About 30-40 percent of potent patients become impotent 5-10 years after RT. It usually does not occur right after radiation therapy but slowly develops over the years. This is different from surgery, where impotence occurs immediately and may improve over time. Problems with erections may be less likely to develop after brachytherapy than after other common forms of treatment. Some studies have found rates of sexual dysfunction to be lower after brachytherapy, but other studies have found that the impotence rates were no lower than with external beam radiation. Advanced age, the use of androgen blockade, as well as comorbidities (vascular diseases, diabetes), contribute to impotence. The better the sexual function before treatment, the more likely patients will maintain function after treatment. Viagra or similar medications help more than half of these patients to regain adequate erection.
Incontinence: Very rarely seen with any form of radiotherapy. Patients who had TURP and undergo brachytherapy have a higher incidence of incontinence. For those patients, IMRT is probably a preferred option.
Other possible late complications: Urethral stricture, hemorrhagic cystitis, rectal/bladder perforation and fistula formation are seen very rarely.