PROSTATE CANCER: RADIATION THERAPY

Radiation therapy is used in a variety of settings to treat prostate cancer. Many prostate cancer patients are benefiting from radiation therapy techniques that decrease side effects and may lead to higher cure rates. What technique is appropriate for you? What are the risks? The following information should help answer these questions and prepare you to discuss radiation therapy with your urologist and/or radiation oncologist.

What is radiation therapy?
Radiation therapy, also sometimes referred to as radiotherapy, is a general term used to describe several types of treatment, including the use of high-powered X-rays, placement of radioactivematerials into the body or injection of a radioactive substance into the bloodstream. These various types of radiation treatments are used in a wide range of settings. These circumstances include primary treatment of localized prostate cancer, secondary treatment for cancer recurring within the region of the prostate and for relief of pain and other symptoms related to prostate cancer that has spread to other parts of the body.

What are the different types of radiation therapy?

External beam radiation therapy (EBRT): This is the most commonly used type of radiation therapy. The emergence of EBRT as a treatment for prostate cancer occurred in the 1950s with the development of high-powered X-ray machines called linear accelerators. Linear accelerators produce very powerful photons (i.e. X-rays) that penetrate deep into the body. These X-rays destroy tumorcells by damaging their DNA. Just as with a diagnostic X-ray, there is a brief exposure to the radiation, typically lasting several minutes. Once the treatment is over, there is no radiation in the patient’s body. The treatment is completely non-invasive, so there is no discomfort to the patient during the delivery of the radiation. EBRT is typically given once per day, five days per week. Primary treatment for localized prostate cancer usually requires about eight weeks of treatment. The use of shorter treatment schedules is being studied.

There are different ways to deliver EBRT. Usually several radiation beams are used to shape the radiation to the prostate, called three-dimensional conformal radiation therapy. The intensity of each beam may be altered to further shape the radiation using a technique called intensity modulated radiation therapy (IMRT). Sometimes image-guidance is used to help locate the prostate each day. Proton beam therapy is another form of EBRT that is used in a few centers in the country to treat prostate cancer. Proton beam is precise like IMRT, only it uses protons instead of photons (X-rays). Recent clinical trials have shown that increasing the dose of radiation, either with photons or protons, can be done safely and leads to improved cancer control.

Brachytherapy: Is also referred to as “seed therapy” or a “prostate implant.” Brachytherapy involves the insertion of a radioactive material, commonly referred to as a source, into the body. Attempts to treat prostate cancer by placing radioactive materials into the prostate date back to the early 20th century. However, the lack of a reliable way to ensure that the radioactive materials were placed in their desired locations limited the use of brachytherapy to treat prostate cancer. In the 1980s, a technique was developed using ultrasound to guide the placement of tiny radioactive “seeds” into the prostate. This technique was first made available in the United States in the late 1980s.

There are two approaches to brachytherapy for prostate cancer: low-dose rate (LDR) and high-dose rate (HDR). Prostate brachytherapy is most commonly performed using the LDR technique. With LDR brachytherapy, the seeds are permanently placed into the prostate. The seeds are temporarily radioactive as the radiation is given off gradually over a period of several weeks to months. After giving off their radioactivity, the seeds remain in the prostate. HDR brachytherapy involves the temporary placement of a highly radioactive source into the prostate. The radiation treatment is given off over a period of minutes and typically repeated two or three times over the course of several days. Both LDR and HDR brachytherapy are usually used alone, but occasionally they may also be combined with EBRT.

An ultrasound study may be performed prior to the day of the procedure to ensure there are no bones interfering with the placement of needles into the prostate. The ultrasound probe is placed into the rectum to obtain pictures of the prostate and surrounding structures. This study is commonly referred to as a transrectal ultrasound (TRUS). The information obtained from the TRUS can also be used to generate a road map for seed implantation. Ultrasound imaging is typically used to define the prostate although newer approaches using CT scan or MRI may be used.

The LDR seed implant is typically an outpatient procedure (i.e. you can go home later in the day) and is performed under anesthesia. Radioactive seeds (which are smaller than a grain of rice) are loaded in individual needles that are passed into the prostate gland through the skin between thescrotum and anus. As the needles penetrate the prostate they are seen on a monitor and can be accurately guided to their predetermined position. Once the position of the needle in the prostate matches the intended position, the needle is withdrawn leaving the seeds behind in the prostate. The radioactivity of the seeds slowly decays during several weeks to months after the procedure, and there are few long-term risks associated with this treatment.

Alternatively, HDR brachytherapy may be utilized to place a highly radioactive source temporarily into the prostate. Narrow hollow plastic tubes called catheters are pre-positioned in the prostate using a technique similar to LDR brachytherapy. The patient is then awakened and typically two or three treatments are given over the next several days after which the catheters are removed. A remote control device is used to move the radioactive material, which rests for a calculated period of time at various positions within each catheter. A computerized treatment-planning program is used to determine the required time the radioactive material must stay at each position and the sequential positioning of the radioactive material at each location needed to achieve coverage of the prostate with the prescribed radiation dose.

Radionuclide therapy: Radioactive substances may also be used for treatment of prostate cancer that has spread to the bones. These radioactive drugs, known as radiopharmaceuticals or radionuclides, are injected intravenously (IV). These radionuclides are absorbed by the bones. The radiation given off is weak and does not penetrate very far into surrounding tissues and organs. A single injection is given in the doctor’s office after which the patient may return home. Additional injections may be given after a period of a few months once the effects of the prior injection have diminished.

What are some of the side effects of radiation therapy?

External beam radiation therapy (EBRT): The principal side effects of EBRT are related to the treated area. Common side effects of EBRT for prostate cancer include increased urinary frequency; mild burning with urination; weakened urinary stream; bowel irritability including mild diarrhea, gas, bowel urgency and tenderness; mild irritation of the skin around the rectum; slightly lower blood counts; and fatigue. Diet modification and medication may be used to manage symptoms. Within one or two months following completion of treatment, most men notice that symptoms disappear. If changes in bladder or bowel function persist, they are typically mild. About 20 percent of men, however, do experience more significant long-term bowel irritability. Relatively rare complications include significant rectal bleeding, bladder irritability and urethral stricture. A decline in sexual function is also a relatively common side effect of radiation. However, the risk of erectile dysfunction(ED) following radiation varies widely, depending on use of other treatments such as hormonal therapies and the presence of other medical conditions that may affect sexual function.

Brachytherapy: Like EBRT, urinary irritation is very common following brachytherapy. Obstructive symptoms including difficulty with urination are somewhat more common, however, as the prostate usually swells due to the insertion of needles into the prostate for the procedure. Less than 10 percent of men will experience complete urinary obstruction within several weeks of the procedure requiring use of a catheter. Usually this problem disappears within weeks as the swelling subsides. Since the radioactive seeds are placed directly into the prostate, short-term bowel side effects are also relatively uncommon. However, as the front part of the rectum lies close to the prostate, over time bowel side effects similar to those of EBRT may occur. As with other radiation treatments, erectile dysfunction may occur.

Radionuclide therapy: The principal side effect of radionuclide therapy is a decrease in blood counts following treatment. Serious side effects including infection and bleeding are fortunately rare. However, an increase in pain may occur in the first several days or weeks after radionuclide therapy but can be managed with increased use of pain medications until the therapy begins to have its desired effect.

Which treatment is appropriate for each stage of prostate cancer?
In order to guide patients in choosing an appropriate treatment, doctors depend in part on an understanding of prognostic factors that suggest how extensive or aggressive the cancer may actually be. Such factors include digital rectal examination (DRE), PSA test, Gleason score and biopsy. Given the impact on prognosis that each of these factors may have, a combination of these factors is often more useful in understanding the potential for treatment success or failure than the use of any one factor alone. Within the realm of clinically localized cancer, a combination of these factors may be used to categorize patients as “low risk,” “intermediate risk” and “high risk” in terms of treatment failure. It is important to note that while prognostic factors are helpful in guiding treatment choices, there is no “cookbook” for selection of treatment, and other factors including age, overall health, urinary and bowel function and each patient’s own concerns about treatment need to be taken into account. Therefore, a thorough discussion with an individual’s urologist, radiation oncologist and medical oncologist is an important part of the decision-making process.

Prostate cancer that has not spread outside the immediate area around the prostate is often referred to as clinically localized cancer. An important distinction within the realm of clinically localized cancer is between prostate cancers confined to the prostate, referred to as organ-confined disease, and prostate cancer that has spread directly outside the prostate or into the seminal vesicles. The term “clinical” is applied to the setting where the determination that cancer has not spread to other sites, including lymph nodes or distant tissues and organs, is based on the findings of physical exam and diagnostic imaging tests that may include CT scan, MRI and/or bone scan. Proof of cancer stage is only obtained by invasive procedures such as surgical removal of the prostate or biopsy.

Treatment of low-risk clinically localized prostate cancer: The “low-risk” category generally includes patients with T1 or T2a cancer (normal examination or small abnormality limited to one side of the prostate), PSA less than 10 ng/ml and/or Gleason grade less than or equal to six. These men are the most likely to have cancer confined to the prostate. Treatment options may include radicalprostatectomy, external beam radiation therapy (EBRT), prostate brachytherapy or, in certain circumstances, active surveillance (observation). Given that almost all men with early detection of prostate cancer are without symptoms, the impact that treatment may have on quality of life is an important consideration.

Treatment of intermediate-risk clinically localized prostate cancer: The “intermediate-risk” category generally includes patients with T2b disease (bulkier abnormality involving more than 50 percent of one side of the prostate), PSA greater than 10 ng/ml but less than or equal to 20 ng/ml and/or Gleason grade seven. In addition, the extent of tumor on biopsy, often referred to as “percent positive biopsies” may help sort out which men in this category have outcomes more similar to the low or high-risk group. Men with just a little cancer found on biopsy might have outcomes more in line with low-risk patients while men with extensive cancer may be at greater risk for treatment failure. Overall, many men in this category may still have cancer confined to the prostate or along the edge of the prostate. The risk of spread outside the prostate is greater, however, than that for men with all low-risk features.

Given the many nuances in the presentation of intermediate-risk disease a number of treatment options may be appropriate. These options may include radical prostatectomy, EBRT, prostate brachytherapy or a combination of EBRT and brachytherapy. A short-course of androgen deprivation therapy, commonly referred to as hormonal therapy, may also have a role in treatment of intermediate-risk prostate cancer when combined with radiation. While in men with high-risk prostate cancer the role of hormonal therapy with radiation is now established, the role in treatment of intermediate-risk prostate cancer remains to be fully defined. One study has suggested a benefit to the addition of six months of hormonal therapy to EBRT in this patient group and therefore at least warrants consideration when radiation therapy is used.

Treatment of high-risk clinically localized prostate cancer: The “high-risk” category includes men with any of the following features: T2c, T3 or T4 disease (abnormal examination on both sides of the prostate or cancer that has spread outside of the prostate as determined by digital rectal examination), PSA greater than 20 ng/ml and/or Gleason grade between eight and 10. Men in this category have a substantial risk of spread of cancer outside of the prostate. Nevertheless, some men in this category do have cancer confined to the prostate and therefore local treatment including prostatectomy may be appropriate. In men deemed to be at greater risk for disease spread, the most standardized radiotherapeutic approach to treatment is the combination of EBRT and hormonal therapy. Other treatments, including combination of EBRT and brachytherapy with or without hormonal therapy, may be considered but the long-term results of newer approaches remain to be fully defined. Several large randomized studies in the United States and Europe have all shown significant benefit to the use of hormonal therapy when combined with EBRT in men with various high-risk features. Recent results confirm a benefit to longer duration hormonal therapy (i.e. two to three years) in men with high-risk or locally advanced prostate cancer. The use ofchemotherapy in this group of men remains to be defined and is now the focus of ongoing national studies. Given the variety of presentations within the high-risk group, the right treatment for any given individual needs to be carefully considered in consultation with a urologist, radiation oncologist, and medical oncologist.

Should radiation therapy be used as treatment following surgical removal of the prostate (prostatectomy)?
External beam radiation therapy (EBRT) may be used following prostatectomy when there is concern that cancer may remain in the region of the prostate. The use of radiation in this setting to destroy residual cancer has previously been sporadic but more recently has gained widespread acceptance. Studies from the United State and Europe have shown benefit to EBRT after prostatectomy in the setting of T3 disease (through the prostate capsule) and/or positive surgical margins, with a recent update demonstrating a survival benefit. The possibility of success with radiation following prostatectomy depends on the likelihood that any remaining cancer is confined to the region of the prostate where radiation is aimed. Therefore, the success rate varies widely depending on the presentation at the time treatment is contemplated. Diagnostic studies may be helpful but unfortunately no test can exclude the possibility of microscopic spread of the cancer. The physician must therefore assess a number of factors including the pretreatment prognostic factors,pathological findings at the time of prostatectomy and the post-surgical PSA history in determining which patients are most likely to have localized cancer versus cancer that has spread (metastasized).

How successful is radiation therapy in the treatment of metastatic cancer?
Radiation is often an effective treatment for preventing or managing symptoms of prostate cancer that has spread. External beam radiation therapy is typically very helpful in decreasing or relieving pain related to prostate cancer that has spread to the bones. A short course of therapy usually no longer than two weeks is sufficient in most cases. In other cases, radiation may be used to prevent debilitating symptoms related to the uncontrolled spread of cancer near critical organs or tissues.

Frequently asked questions:

How do I know if radiation therapy is the right treatment for me?

Talk to your urologist and/or radiation oncologist. Every tumor is different, and it is important that your doctor evaluate all aspects of your tumor (such as localization, size, position) in order to prescribe the best treatment.

Will radiation therapy affect my sexual function?

Possibly. The risk of erectile dysfunction following radiation varies widely, and is dependent on the use of other treatments—such as hormonal therapy—and other medical conditions (such as diabetes and heart disease) that may affect sexual function.

Since the doctors aren’t removing my tumor, how will I know if it’s gone?

Follow up testing is very important in order to be sure that the tumor has been killed. You may require regular PSA testing, digital rectal examination, and occasional imaging to be sure that the cancer has not recurred. Sometimes, you may require additional treatment if the initial radiation does not work.