Prostate Cancer: Radiation, Brachytherapy and Radiopharmaceuticals

Photograph of a person undergoing radiation therapy.

Radiation is a powerful tool at doctors’ disposal to treat and even cure prostate cancer.

The prostate gland wraps around the urethra in men and provides the liquid portion of semen. This gland is necessary for reproduction, and cancer or damage from cancer treatments may cause impotence and/or incontinence. Using radiation to kill cancer cells may still cause side effects, but ideally, they are less severe than those from surgery or other more invasive treatments.

Radiation therapy can be performed via external beam therapy (EBRT) or the placement of radioactive seeds into the prostate (prostate brachytherapy). Radioactive drugs are called “radiopharmaceuticals” and may also be part of therapy for prostate cancer.

An X-ray machine uses a low-energy radiation beam to take a picture of a portion of the body. Radiation therapy machines put out high-energy beams that can be focused very precisely to deliver treatment to a site. The radiation does not "burn out" cancer, but damages the cells' DNA, which causes the cancer cells to die. This process can take some time to occur after the radiation treatments have been given.

The radiation passes directly through the tissues in EBRT. Radiation treatment used today delivers very little energy to normal tissues. It just passes through. Most of the energy is able to be focused and delivered directly to the area of the prostate gland containing cancer. This process minimizes damage to healthy tissue.

EBRT can be administered in a variety of different ways including 3-D CRT, IMRT, and others. EBRT is classically administered in brief daily treatments, 5 days a week over several weeks. While the radiation does not remain in the body with this approach, the effect of the daily fractions is cumulative. Newer forms of EBRT using machines called CyberKnife allow the treatment to be completed in shorter periods of time.

A recently popular technique of EBRT is called proton beam radiation, which can theoretically more closely focus on the area being treated. Proton beam radiation therapy is more expensive. Its side effects presently appear similar to those discussed for standard radiation therapy, except for an increased incidence of gastrointestinal side effects with proton beam radiation. Studies comparing the effectiveness and overall results of conventional radiation therapy versus proton beam therapy have not been completed yet.

Radiation therapy to the prostate gland by external beam technique may cause fatigue and bladder and/or rectal irritation. One may experience frequency of urination or stools and blood in the urine or stools. These effects are usually temporary but may recur or persist long after treatments are finished. Radiation damage to adjacent tissues can cause skin irritation and local hair loss. Delayed onset of impotence can occur after radiation therapy due to its effect on normal tissues, including nerves adjacent to the prostate. Radiation therapy may be given alone or in combination with hormonal therapy, which can also shrink up the prostate gland, thereby reducing the size of the radiation area or field that needs to be treated. The NCCN guidelines recommend that patients with high-risk and very-high-risk prostate cancer receive neoadjuvant/concomitant/adjuvant hormone therapy (androgen deprivation therapy [ADT]) for a total of 2-3 years if the overall health of the patient permits and that patients with intermediate-risk prostate cancer be considered for 4-6 months of neoadjuvant/concomitant/adjuvant hormone therapy (ADT). Pelvic lymph node radiation may be considered for high-risk and very high-risk prostate cancer patients. Patients with low-risk prostate cancers should not receive ADT or lymph node radiation.

EBRT is appropriate for men who are candidates for radical prostatectomy but do not wish to undergo the surgery or who are not ideal surgical candidates.

EBRT may also be used to treat recurrent prostate cancer localized to the prostate bed (where the prostate was before it was removed surgically). It is also used to treat bone metastases (spread of the prostate cancer to the bone) to reduce pain or if the cancer is pressing on important structures, including the spinal cord.

Brachytherapy refers to the use of radiation sources -- sometimes referred to as seeds -- placed into the prostate gland. Brachytherapy may be done with what is called low-dose rate (LDR) or high-dose rated (HDR) technique. In LDR brachytherapy, types of radioactive seeds, which only briefly put out a form of radiation that does not travel very far through tissues, are permanently implanted in the prostate gland. High-dose rate (HDR) brachytherapy involves the temporary placement of different types of seeds or sources that give off higher amounts of more penetrating radiation. These seeds administer higher doses of radiation for longer periods of time and cannot be left in the body.

Such sources are placed in the prostate gland through surgically implanted tubes. These HDR sources are removed along with the tubes in a couple of days. In LDR brachytherapy, the seeds are placed in the operating room using image guidance to ensure the seeds go into the right places -- 40-100 seeds may be placed. With LDR, you can go home shortly after you wake up after the procedure. In HDR, you must stay at the hospital for a few days. If the prostate gland is large, hormonal treatment (ADT) may be used to shrink the gland before the brachytherapy is done. Brachytherapy may also be combined with external beam radiation therapy to further increase the dose of radiation therapy given to the prostate gland.

Brachytherapy can cause some blood in the urine or semen. It can cause a feeling similar to constipation due to the swelling of the prostate gland. One can also experience transient troubles urinating, called urinary retention, related to swelling of the prostate gland, that may require short-term catheter placement. It can also make you feel that you want to move your bowels more often. There may be some long-term problems with irritation of the rectum, difficulty urinating due to scar tissue formation, and even delayed-onset impotence.

The NCCN guidelines version 2.2017 indicate that brachytherapy can be used as a single therapy (monotherapy) in patients with low-risk cancers and select individuals with low-volume intermediate risk cancers. Intermediate-risk prostate cancers can be treated by a combination of brachytherapy and EBRT +/- 4-6 months of neoadjuvant, concomitant/adjuvant ADT.

High-risk patients can be treated with a combination of EBRT and brachytherapy +/- 2-3 years of neoadjuvant/concomitant/adjuvant ADT.

Patients with a very large prostate or very small prostate, those with symptoms of bladder outlet obstruction, or who have had a previous transurethral resection of the prostate (TURP) are more difficult to treat and have a greater risk of side effects.

Brachytherapy can be used as a salvage therapy for recurrent/persistent prostate cancer after external beam radiation therapy (EBRT). The risk of side effects is increased when used as a salvage therapy.

The use of substances that are radioactive as a treatment for bone metastases has been tried for years. Strontium-89 and samarium-153 have been used in the past. They decrease pain in patients with prostate cancer with bone metastases but they do not prolong life; these medications lower levels of healthy blood cells in patients who receive them.

Recently a form of radium called Ra-223 (Xofigo) has been approved for use in prostate cancer patients with metastases to the bone but not to other internal organs. Radium is like calcium and it migrates to the bone where it acts locally. As an alpha emitter, radiation from radium does not travel far enough in the body to damage other healthy tissues. Unlike bisphosphonates, the use of this agent reduces pain and can prolong survival. It is administered by an injection into a vein. It can cause nausea, diarrhea, and low blood counts.