What are externalbeam and conformal externalbeam radiation therapies What are the side effects of EBRT

External-beam radiation therapy (EBRT) is the use of radiation therapy to kill or inactivate cancer cells. The total radiation dose is given in separate individual treatments, known as fractionation. Cancer cells are most sensitive to radiation at different phases in their growth.

By giving the radiation on a daily basis, the radiation oncologist hopes to catch the cancer cells in the sensitive phases of growth and also to prevent the cells from having time to recover from the radiation damage. Con-formal EBRT uses CT images to help better visualize the radiation targets and the normal tissues. With three dimensional images, the radiation oncologist can identify critical structures, such as the bladder, the rectum, and the hip bones. This allows the radiation oncologist to deliver more radiation (72-82 Gy as opposed to 66-72 Gy with standard EBRT) to the prostate tissue but decrease the amount of normal tissue that is irradiated. The advantage of conformal EBRT over EBRT is that conformal EBRT causes less rectal and urinary irritation. The construction of an immobilization device (cradle) and the placement of small, permanent tattoos ensure that you are properly positioned for the radiation treatment each day. Through the assistance of computers, the radiation oncologist can define an acceptable dose distribution to the prostate and surrounding tissues, and the computer determines the appropriate beam configuration to create this desired distribution.

By giving the radiation on a daily basis, the radiation oncologist hopes to catch the cancer cells in the sensitive phases of growth and also to prevent the cells from having time to recover from the radiation damage.

Who is a candidate for conformal EBRT?

Men who are candidates for conventional EBRT are also candidates for conformal EBRT. Similar to other curative treatments, the ideal patient has a life expectancy of 7 to 10 years. In higher-risk patients, the increased radiation dose used with conformal EBRT causes a significantly better decrease in PSA progression than the dose used in conventional EBRT. There does not appear to be a PSA progression-free survival benefit with conformal EBRT when compared with conventional EBRT in patients who have low-risk prostate cancer. Men who have a PSA level > 10 ng/mL or with a tumor that is clinical stage T3 are the most likely to benefit from the higher radiation doses that can be achieved with confor-mal EBRT. They may benefit from combination therapy, such as hormone therapy for 6 months plus EBRT. For patients with locally advanced or high-grade disease (Gleason score > 7) studies have demonstrated that 2 to 3 years of postradiation adjuvant therapy helps improve survival. The amount of radiation and the field of radiation differ for each individual and depend on the clinical stage and the Gleason grade. Contraindications to EBRT include a history of inflammatory bowel disease, such as Crohn's disease and ulcerative colitis or a history of prior pelvic radiotherapy.

What are the side effects and risks of EBRT and conformal EBRT?

The side effects of EBRT or conformal EBRT can be either acute (occurring within 90 days after EBRT) or late (occurring > 90 days after EBRT). The severity of the side effects varies with the total and the daily radiation dose, the type of treatment, the site of treatment, and the individual's tolerance. The most commonly noted side effects include changes in bowel habits, bowel bleeding, skin irritation, edema, fatigue, and urinary symptoms, including dysuria, frequency, hesitancy, and nocturia. Less commonly, swelling of the legs, scrotum, or penis may occur. Late side effects include persistence of bowel dysfunction, persistence of urinary symptoms, urinary bleeding, urethral stricture, and erectile dysfunction.

Bowel Changes

A change in bowel habits is one of the more common side effects of EBRT. Patients may develop diarrhea, abdominal cramping, the feeling of needing to have a bowel movement, rectal pain, and bleeding. Usually, if these side effects are going to occur, they do so in the second or third week of treatment.

Rectal pain can be treated with warm sitz baths, hydro-cortisone-containing creams (ProctoFoam HC, Corti-foam), or anti-inflammatory suppositories (Anu-sol, Rowasa).

Late bowel effects include persistent changes in bowel function, rectal fistula, or perforation (a hole in the rectum), and bleeding. Rectal fistula and perforation are rare and often require surgical treatment.

Skin Irritation

How skin tolerates radiation depends on the dose of radiation used and the location of the skin affected. The perineum and the fold under the buttocks are very sensitive and may become red, flake, or drain fluid. To prevent further irritation, avoid applying soaps, deodorants, perfumes, powders, cosmetics, or lotions to the irritated skin. After you wash the area, gently blot it dry. Cotton underwear and loose fitting clothes can help prevent further irritation. If the irritated skin is dry, topical therapies, such as petroleum jelly (Vaseline), lanolin, zinc oxide, Desitin, Aquaphor, Procto-Foam, and corn starch, can be applied.


Edema of the legs, scrotum, and penis may rarely occur, but when it does, it is more common in those who have undergone prior pelvic lymph node dissection. Lower extremity edema can be treated with supportive stockings, TED hose, and elevation of feet when sitting and lying down. Penile and scrotal edema is often difficult to treat.


An abnormal passage or communication, usually between two internal organs, or leading from an internal organ to the surface of the body.

How skin tolerates radiation depends on the dose of radiation used and the location of the skin affected.

Urinary Symptoms

The genitourinary symptoms of dysuria, frequency, hesitancy, and nocturia are related to changes that occur in the bladder and urethra that result from radiation exposure. The bladder may not hold much urine because of the irritation and scarring, and irritation of the bladder lining may make it more prone to bleeding. Bladder inflammation usually occurs about 3 to 5 weeks into the radiation treatments and gradually subsides about 2 to 8 weeks after the completion of radiation treatments. Urinary anesthetics (phenazopyridine HCL [Pyridium]) and bladder relaxants (antimuscarinic agents) may be helpful in decreasing the urinary frequency.

What is the success rate with EBRT/conformal EBRT? The success rate varies with the initial PSA level. In one study, 89 to 92% of men treated with conformal EBRT whose pretreatment PSA was < 10 ng/mL showed no increase in PSA level at 5 years. Those with a pretreat-ment PSA of 10 to 19.9 ng/mL had an 82 to 86% chance of no increase in PSA level at 5 years, compared with a 26 to 63% chance of no increase in PSA at 5 years in men with a pretreatment PSA of > 20 ng/mL.

Men with T1 and T2 tumors have survival rates that are comparable to that with radical prostatectomy. In such individuals, the clinical tumor-free survival is 96% at 5 years and 86% at 10 years.

24. What if I am incontinent after radical prostatectomy or radiation therapy? What if I have erectile dysfunction after radical prostatectomy or EBRT or brachytherapy?

When seeking treatment for prostate cancer, many men are very concerned about the effects of the treatment on erectile function. Basically, all of the treatment options carry a risk of erectile dysfunction; however, they differ in how soon after treatment the erectile dysfunction occurs and how likely it is to occur. If you are already having trouble with erections, none of the treatments for prostate cancer will improve your erections. The incidence of erectile dysfunction associated with radical prostatectomy varies with patient age, erectile function before surgery, nerve-sparing status, and the surgeon's technical ability to perform a nerve-sparing radical prostatectomy. The incidence of erectile dysfunction after a nerve-sparing radical prostatectomy varies from 16 to 82%. When it occurs with radical prostatectomy, erectile dysfunction is immediate and is related to damage of the pelvic nerves, which travel along the outside edge of the prostate. Men who have undergone nervesparing radical prostatectomies and who are impotent after surgery may experience return of their erectile function over the following 12 months.

The incidence of erectile dysfunction after EBRT ranges from 32 to 67% and is caused by radiation-related damage to the arteries. Unlike with surgery, the erectile dysfunction occurs a year or more after the radiation. The incidence of erectile dysfunction is 15 to 31% in the first year after EBRT and 40 to 62% at 5 years after EBRT.

The incidence of erectile dysfunction after interstitial seed therapy with or without medium-dose EBRT ranges from 6 to 50%. Similar to EBRT, the erectile dysfunction tends to occur later than with radical prostatectomy.

Hormone therapy with the LHRH analogues or orchiectomy also causes erectile dysfunction, as well as loss of interest in sex in most men. This loss of libido is related to the loss of testosterone, but why the loss of testosterone causes troubles with erections is not well known.

Penile prosthesis

A device that is surgically placed into the penis that allows a man with erectile dysfunction to have an erection.

Various therapies are available for the treatment of erectile dysfunction, including oral, intraurethral, and injection therapies; the vacuum device; and the penile prosthesis, which is a device that is surgically placed into the penis and allows an impotent individual to have an erection (see Questions 75, 80-100).

In the treatment of post-radical prostatectomy erectile dysfunction, the effectiveness of oral PDE-5 Inhibitors (Viagra, Cialis, Levitra) varies with nerve-sparing status:

Bilateral nerve sparing: 71% success rate Unilateral nerve sparing: 50% success rate Non-nerve sparing: 15% success rate

In men with EBRT-associated erectile dysfunction, oral PDE-5 Inhibitors work in about 70% of individuals. In men who have erectile dysfunction associated with interstitial seed therapy, PDE-5 Inhibitors have a success rate of approximately 80% (see Question 81 for use of PDE-5 inhibitors).

If oral therapy is not effective or if you have contraindications to oral therapy there are a variety of other medications/devices that may allow you to achieve an adequate erection for satisfactory sexual function. See Questions 84-99.

Urinary incontinence, the uncontrolled loss of urine, is one of the most bothersome risks of prostate cancer treatment. Although it is more commonly associated with radical prostatectomy, it may also occur after interstitial seed therapy, EBRT, and cryotherapy. Urinary incontinence may lead to anxiety, hopelessness, and loss of self-control and self-esteem. Fear of leakage may limit social activities and participation in sex. If you are experiencing these feelings, you should discuss this with your doctor and spouse or significant other.

If you experience persistent urinary incontinence after surgery or radiation therapy, your doctor will want to identify the degree and the type of incontinence. You will be asked questions regarding the number of pads you use per day, what activities precipitate the incontinence, how frequently you urinate, if you have frequency or urgency, how strong your force of urine stream is, if you feel that you are emptying your bladder well, and what types and how much fluid you are drinking. The doctor may check to make sure that you are emptying your bladder well. This is usually done by having you urinate and then scanning your bladder with a small ultrasound probe to determine how much urine is left behind. Normally, less than 30 cc (one tablespoon) remains after urination.

Several different types of urinary incontinence exist, and the different types may coexist. The treatment of urinary incontinence varies with the type, and the types that may be encountered in men being treated for prostate cancer includes stress, overflow, and urge incontinence. Men who have undergone radical prostatectomy typically experience a type of stress incontinence called intrinsic sphincter deficiency. Stress incontinence may also occur after interstitial seed therapy and is much more common if a TURP of the prostate was performed in the past. In men, urinary control is primarily at the bladder outlet by the internal sphincter muscle. This muscle remains closed and opens only during urination. An additional muscle, the external sphincter, is located further away from the bladder and is the back up muscle. The external sphincter is the muscle that you contract when you feel the urge to urinate and there is no bathroom in sight. During a radical prostatectomy, the internal sphincter is often damaged with removal of the prostate because it lies just at the top of the prostate. Continence then depends on the ability of the remaining urethra to close (coapt) and on the external sphincter.

Urge incontinence

Incontinence associated with urgency.

Urge incontinence is the involuntary loss of urine associated with the urge to urinate and is related to an over-active bladder. Although less common than intrinsic sphincter deficiency in men who have undergone radical prostatectomy, it may be present alone or in conjunction with intrinsic sphincter deficiency. Overactive bladder and decreased bladder capacity are more common in men who have undergone EBRT for prostate cancer. Urge incontinence can be treated with antimuscarinic agents, medications which relax the bladder muscle.

Overflow incontinence

A condition in which the bladder retains urine after voiding, and as a result, urine leaks out, similar to a full cup under the faucet.

Overflow incontinence is the involuntary loss of urine related to incomplete emptying of the bladder. After radical prostatectomy, this may occur if significant scarring (a bladder neck contracture) is present at the bladder outlet area. Treatment of the bladder neck contracture often relieves the overflow incontinence. Other symptoms include a weak urine stream and the feeling of incomplete bladder emptying. With overflow incontinence, the bladder scanner would demonstrate a large amount of urine left in the bladder after urinating. Urethral strictures after EBRT may also cause overflow incontinence; dilation of such strictures also improves the overflow incontinence. Urethral strictures tend to recur, and daily in and out passage of a catheter beyond the site of the stricture helps prevent recurrence of the stricture. Swelling of the prostate after interstitial seed therapy may cause voiding troubles, which if unrecognized, may lead to overflow incontinence. Initial treatment of overflow incontinence after seed therapy is with clean intermittent catheterization, and possibly the addition of an alpha-blocker (Hytrin, Cardura, Flomax, Rapaflo) and a nonsteroidal anti-inflammatory.

Your doctor may wish to perform further studies (see urodynamics in Question 34) to further identify the cause of your incontinence.

Treatment Options

Once the cause and the severity of the urinary incontinence has been assessed, you can then embark on treatment. In all cases of incontinence, it is important to make sure that you are voiding regularly, that is, every 3 hours, and avoiding alcohol and caffeinated fluids. Caffeine and alcohol cause the kidneys to make more urine and are bladder irritants. It may also be helpful to avoid acidic foods and foods with a lot of hot spices because these may also act as bladder irritants.

If a bladder neck contracture is present, treatment may consist of dilation or incision. There is a risk of stress incontinence after incision of a bladder neck contracture. If overflow incontinence occurs after interstitial seed therapy, your doctor may give you a medication called an alpha-blocker to relax the prostate, an anti-inflammatory drug, and prescribe clean intermittent catheterization until you are voiding on your own. Usually, voiding troubles of this nature after interstitial seed therapy resolve with time, so additional treatment is rarely needed. Your doctor will be quite reluctant to do anything more aggressive for the first 6 months after the placement of the seeds because of the high risk of urinary incontinence with a TURP.

Overactive bladder is treated with medications that relax the bladder muscle, the most common of which are called antimuscarinics, including:

• oxybutynin (Ditropan)

• tolterodine (Detrol)

• solifenacin (Vesicare)

• trospium chloride (Sanctura)

• darifenacin (Enablex)

• oxybutynin patch (Oxytrol)

• oxybutynin gel (Gelnique)

• fesoterodine (Toviaz)

More common side effects of these medications include dry mouth, facial flushing, constipation, and, in some patients, blurry vision. Dry mouth and constipation rates are decreased with the long-acting formulations.

A variety of treatment options exist for stress incontinence, including pelvic floor muscle exercises, a penile clamp, collagen injection, an artificial sphincter, and a male urethral sling.

Pelvic floor muscle exercises: Pelvic floor muscle exercises are intended to strengthen these muscles. To identify these muscles, simply try stopping your urine stream while you are urinating. The exercises involve repetitive contracting and relaxing of the pelvic muscles at least 20 times per day every day of the week. Pelvic floor stimulation and biofeedback allow you to identify these muscles better and to monitor the strength of the contractions.

Penile clamp: Several penile clamps are available, and all of them have the same principle, which is to compress the urethra to prevent urinary leakage (Figure 14). They should be worn for brief periods of time only and should not be left on all day. If they are left on for long periods of time, they may cause damage to the penile skin and the urethra. The clamp needs to be removed if you need to urinate. The penile clamp should not take the place of pelvic floor muscle exercises; rather, it should be used as a backup measure. For instance, if you are going out to dinner and want to make certain there is no leakage, then you should use the penile clamp.

Collagen injection: Collagen is a chemical that is found throughout your body. The collagen that is being used to treat urinary incontinence is derived from a cow. Because it comes from a source outside of your body,

Metal frame

Metal frame

Radiation Penis Clamp
Foam rubber Figure 14 Penile clamp.

you must have skin testing to make sure that you are not allergic to the collagen. The collagen is injected into the bladder neck and the proximal urethra to make the urethra come together (coapt) (Figure 15). The amount of collagen injected at each treatment varies from person to person. The collagen injection can be performed in the urologist's office under local anesthesia or in the operating room under spinal or general anesthesia. More commonly, the collagen is injected retrograde through a cystoscope that is placed through the penile urethra and positioned just before the injection site. A long, thin needle is then passed through the scope, advanced into the urethra at the appropriate location where the collagen

Figure 15 Location of collagen injection.

is injected. The collagen is injected at several sites in the urethra until the urologist is satisfied with the amount of urethral coaptation. Some urologists prefer to perform the procedure antegrade. A small needle is passed through the lower abdominal skin into the bladder. A small wire is then placed through the needle into the bladder, and the needle is removed. Small dilators are then placed over the wire to make an opening that is large enough for the cystoscope, which is then placed through the opening in the abdominal skin into the bladder. The bladder neck is identified and the collagen injected. Often, more than one treatment session is needed. Typically three to four injections, each 4 weeks apart, are necessary. It is also possible that repeat collagen injections will be necessary over the long term. Collagen injections provide a continence rate of about 26% in postprostatectomy incontinence and a reduction in the number of pads used per day in an additional 37% of men.

The advantages of collagen injection are that it is minimally invasive, it is repeatable, it is associated with a short recovery period, and if it fails, it does not prevent you from pursuing other forms of therapy. Disadvantages of collagen therapy are that only a small percentage of men become totally dry, a small number of men develop a urinary tract infection, and 11% of men have transient urinary retention requiring clean intermittent catheteri-zation. Permanent retention has not been reported.

Lastly, some individuals will experience transient dysuria (discomfort with voiding) and urgency after the procedure. The best candidates for collagen are men who have higher Valsalva leak point pressures (60 cm H2O), who do not have overactive bladders, have not had prior radiation or cryotherapy, and who have not had a vigorous incision of a bladder neck contracture.

Artificial urinary sphincter. The artificial sphincter is a mechanical device that is comprised of a cuff that is placed around the urethra, a pump that is placed in the scrotum, and a reservoir that is positioned in the abdomen (Figures 16 and 17). All of these parts and the tubing that connects them are buried under the skin and are not visible. The cuff remains filled with sterile fluid and compresses the urethra. When you wish to urinate, the pump is pressed, which transfers fluid out of the cuff, allowing you to urinate. The cuff automatically refills to compress the urethra. Placement of the artificial sphincter requires general or spinal anesthesia and an overnight hospital stay. Initially after the surgery, the sphincter is

Ams Artificial Urinary Sphincter

Figure 16 AMS Sphincter 800 urinary prosthesis.

Courtesy of American Medical Systems®, Inc. Minnetonka, Minnesota (www.AmericanMedicalSystems.com).

Figure 16 AMS Sphincter 800 urinary prosthesis.

Courtesy of American Medical Systems®, Inc. Minnetonka, Minnesota (www.AmericanMedicalSystems.com).

Pressure-regulating balloon

Pressure-regulating balloon

Control pump

Figure 17 Location of artifical sphincter.

Control pump

Figure 17 Location of artifical sphincter.

Courtesy of American Medical Systems®, Inc. Minnetonka, Minnesota (www.AmericanMedicalSystems.com).

deactivated so that it doesn't work. It will be activated 4 to 6 weeks after surgery, when the tissues have healed and the swelling and sensitivity have subsided. The artificial sphincter provides continence rates of 20 to 90%, including men who are either totally dry or who use one pad per day. The sphincter can be used after collagen has failed. Disadvantages of the sphincter include mechanical malfunction rates of 10 to 15%, erosion rates of 0 to 5%, and infection rates of 3%. The cuff may erode, or move, into the urethra or through the skin, and other parts of the sphincter may erode into the skin or other areas. If there is an erosion, the device must be removed. Similarly, if the sphincter becomes infected, it must be removed. It is very important that a urodynamic study be performed before the sphincter is placed to make sure that the bladder holds an adequate amount of urine at low pressures and to identify an overactive bladder, which would require additional treatment.

Male sling. The fascial sling has been used for several years in women with stress incontinence and has proved to be a successful and durable procedure. Because of its success in women, it has been used more recently in men who are incontinent after radical prostatectomy. The sling may be derived from the patient's own tissues, from a synthetic material, or from cadavers. The goal of the sling is to place tissue under the urethra to act as a buttress or a hammock. The tissue is anchored to either the abdominal wall or the pubic bone.

Success rates with the male sling vary, but about 50% will be dry with a single procedure and retightening of the sling in those who are incontinent after the initial surgery can improve the success rate. In a long-term study, 64% of patients were improved and required two or fewer pads per day after the sling and 36% required zero pads per day. This is a surgical procedure that usually involves an overnight stay in the hospital. Urinary retention may occur that requires CIC over the short term and loosening of the sling if persistent. Complications of surgery include the need for revision, erosion of the sling, and infection.

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