Bone metastases are tumors that have spread from the original cancer site in the prostate gland to the bones. The most common bone sites for them to develop are in the pelvis, spine, thighs and ribs. However, they can develop in any bone anywhere in your body.  Bone metastases can become extremely painful. If you start experiencing bone pain you must tell your doctor.

Normal bone is constantly being remodeled, or reabsorbed and then reformed. Simply put, bone is broken down into its basic parts and then re-built. Prostate cancer disrupts the balance between the osteoclast cells that break down or reabsorb the old bone and the osteoblast cells that create new bone. When the balance is disrupted, tumors develop that can cause fractures, spinal compression, severe pain, weakness, numbness and difficulty urinating. Bone metastases can also cause hypercalcemia, which is abnormally high levels of calcium in the blood causing constipation; nausea; pain; poor appetite; vomiting; kidney problems with flank pain; frequent thirst; frequent urination and kidney stones.

Detecting Bone Metastases

Since bone metastases symptoms vary from man to man, it is important to correctly distinguish bone metastases from other conditions such as arthritis. If you experience bone pain it is important to tell your doctor. X-rays can diagnose bone metastases best, but bone scans, CT scans, PET scans, MRIs and blood tests can also contribute to an accurate diagnosis.

If bone metastases go without treatment, a man with castrate resistant prostate cancer is likely to experience approximately 1.5 skeletal related events (SREs) annually (Citation: Saad F, Gleason DM, Murray R, etal., J Natl Cancer Inst. 2002;94;1451468) with a median time to the first SRE of 10.6 months (Citation: Saad F, Gleason DM, Murray R, etal., J Natl Cancer Inst. 2002;94:1458-1469).

Early detection of bone metastases allows more effective treatment to delay bone pain and other complications.

Bone Metastases need to be treated not only because they can cause severe pain, but because they also cause bones to weaken and fracture. Uncontrolled progression of bones metastases can completely disable a man. Bone metastases can cause spinal cord compression that can lead to paralysis, even death.  Additionally, bone metastases can invade bone marrow hampering the generation of new red blood cells.

Preventing and Treating Bone Metastases

There are a number of different treatments that will affect bone metastases, including chemotherapy, hormonal therapy (ADT), radiation therapy, and bisphosphonates. All these therapies can slow progression and growth of bone metastases.

Both radiation therapy and bisphosphonates are designed to target bone metastases.

  • External Beam Radiation Therapy (EBRT) can be aimed at sites of painful bone metastases (spot radiation). EBRT relieves pain in the majority of men and is most useful for treatment when there are only one or two sites causing pain. When there are more than one or two sites, a systemic treatment – one that circulates through your body – is preferable.
  • Radiopharmaceuticals, are a systemic treatment that has been recently approved by the FDA. These drugs are administered by intravenous infusion (IV)

Radiopharmaceutical drugs usually relieve pain from bone metastases. They travel throughout the skeleton and are able to directly target the metastases in the bone so they are most effective for men with a number of different and diffuse painful bone metastases.

The newest radiopharmaceutical approved for bone metastases caused by prostate cancer is Radium (RA) 223 dichloride (Trade name: Xofigo®)

The FDA approved Xofigo in May of 2013.  In a clinical trial of 809 men with castration-resistant prostate cancer that had spread to their bones, but not to other organs, the men who received RA 223 lived an average of 14 months compared to just over 11 months for men who received a placebo injection. They also reported significant palliative benefit (pain relief).

Radiopharmaceuticals have shown themselves to be very effective in relieving severe pain.

Radium 223 is a systematic treatment mimics calcium that binds with minerals in the bone to deliver radiation directly to the bone tumors while limiting the damage to the surrounding normal tissues.  Since it is systemic it can be used to treat multiple bone metastases in different parts of the body.

Radium 223 is administered once a month as an IV injection into a vein.  The IV infusion should be slow, lasting at least more than one minute.  The dosage is variable depending upon the body weight of the man.  The dosage level 50 kBq/kg body weight or 1.35 microcurie/kg body weight.  The larger the man, the more radium 223 required.

The most common side effects of Radium 223 are:

  • Nausea
  • Diarrhea
  • Vomiting
  • Swelling of the leg, ankle, or foot (edema).
  • Anemia
  • Lymphocytopenia
  • Leukopenia
  • Thrombocytopenia
  • Neutropenia

RA 223 is a breakthrough treatment.  At this time a full treatment protocol consists of six treatments.  The next question to be faced is, can it be used multiple times?  In the best-case situation this is a question that will need to be answered by additional clinical trials. Alternatively, there is an excellent chance that we will have an answer to this question by reviewing the clinical practices of our doctors as they search for the optimum treatment protocols. Although the current literature states that only six doses are considered safe, this is not to say that additional doses would necessarily be unsafe.

Unlike other drugs used in the treatment of men with advanced prostate cancer, the body does not metabolize RA 223; it decays naturally and is expelled.  During the first week after the injection 63% is excreted in the fecal matter.  Cleaning your toilet bowl is important and should be done while limiting contact with the water in the toilet.  Not discussed, but equally important, is to take care that after moving your bowels you clean yourself thoroughly and don’t allow anyone to have a chance contact with the used toilet paper.  Proper hygiene practice includes:

  • Flush the toilet several times after each use;
  • Wipe up and flush any spilled fecal matter;
  • Wash your hands after using or cleaning a toilet;
  • Wash soiled clothes and bed linens separately from other laundry.

Prior to the approval of RA 223 other useful radiopharmaceuticals were available and which still may be used. RA 223 is a superior treatment because it does not have a long-range (distance) effect on surrounding healthy cells, while older radiopharmaceuticals spread beyond the tumor location.  Additionally, RA 223 is the only treatment in this class that has demonstrated any survival advantage.

Other radiopharmaceuticals include Strontium-89 (Metastron) and Samarium-153 (Quadramet), which specifically target bone lesions.   As well, there are two other radioactive isotopes, rhenium 86 and rhenium 188, which have been utilized less frequently to treat bone metastasis caused by prostate cancer.

Prior to the approval of Radium 223, Metastron (strontium-89) had been the most common radiopharmaceutical for treating men with prostate cancer that has metastasized to the bone. Men with advanced prostate cancer who are responding to chemotherapy appear to have a better chance of survival if bone metastases are treated with strontium-89 every six weeks in conjunction with a chemotherapy drug.

Dosages of radiopharmaceuticals vary with the individual and the type of treatment. Dosages of radioactive materials are expressed in units called millicuries.

Strontium 89 is injected into a vein. The usual dosage is 4 millicuries, depending on age, body size, and blood cell counts. Repeated doses may be required.

Samarium 153 is also injected slowly into a vein. The usual dosage of samarium 153 is 1 millicurie per kg (0.45 millicurie per lb) of body weight. Repeated doses may be necessary. Because samarium 153 may accumulate in the bladder, it is important to drink plenty of liquid prior to treatment and to urinate often after treatment.

Strontium-89 and samarium 153 may temporarily lower the number of white blood cells, which you need to fight infections. The number of blood platelets, which are important for proper blood clotting, may also be lowered.

Strontium-89 and samarium 153 are excreted in the urine. To prevent radioactive contamination, you should follow special measures for one week after receiving strontium-89 and for 12 hours after receiving samarium 153:

  • Use a toilet rather than a urinal;
  • Flush the toilet several times after each use;
  • Wipe up and flush any spilled urine or blood;
  • Wash your hands after using or cleaning a toilet;
  • Wash soiled clothes and bed linens separately from other laundry.

If you suffer with bladder control problems you must take special measures following treatment to prevent contamination with radioactive urine.  Speak to your doctor about this prior to treatment.

While there are no warnings regarding radiation exposure to people around you, if you are involved with a child, a pregnant woman or other vulnerable individual, you might want to speak with your doctor about any particular risk.

Flushing of the skin and transient increased bone pain are among the common side effects of strontium-89.

Signs of infection due to low white blood cell counts after treatment with strontium-89 and samarium 153 are fever, chills, cough or hoarseness, lower back or side pain, painful or difficult urination.  Be sure to see a doctor if these symptoms persist.

Signs of low platelet count after treatment with strontium-89 and samarium 153 include, bleeding or bruising, black, tar-like stools, blood in urine or stools and tiny red spots on the skin.

Radiation therapy or other anticancer drugs may amplify the harmful effects of strontium 89 and samarium 153 on the bone marrow. Medicines containing calcium may prevent strontium 89 from being absorbed by bone tissue. Bisphosphonates may also prevent samarium 153 from working effectively.