Osteosarcoma (bone cancer) is the topic of this review article. It’s a rare form of cancer with only about new 560 cases diagnosed each year. But it can have devastating effects and a poor prognosis, so articles like this are very helpful in keeping us up-to-date on the diagnosis and treatment of this disease.
Children and teens are affected most often because of how fast they are growing. Rapid turnover of bone cells goes haywire when tumor-suppressor genes that normally regulate the bone cell cycle get turned off or get side tracked. It doesn’t look like osteosarcoma is an inherited condition, but there are some genetics involved with chromosomal abnormalities and of course, mutation of the tumor-suppressor gene.
There are different subtypes of osteosarcoma. These are divided into conventional, telangiectatic, and low-grade intramedullary. These subtypes are based on the location of the tumor (at the end of the bones versus in the long shaft of the bone), size and shape of the tumor cells, and type of bone cells affected (osteoblasts versus osteoclasts or mixture of both). Conventional osteosarcoma (also known as classic osteosarcoma) is the most common type presenting in 80 per cent of all cases.
There are also surface osteosarcomas. These tumors form on the surface of the long bones rather than inside the intramedullary canal of the bone. Surface osteosarcomas are divided into subgroups labeled parosteal, periosteal, and high-grade. Young adults between the ages of 20 and 30 are affected most often by surface osteosarcomas.
Red flag symptoms for osteosarcoma alert the patient that there is a problem. These include joint pain and loss of joint motion. Sometimes there’s a bony bump that can be felt. There may be redness and warmth of the skin over the affected area. Fastest growing bones are affected most often. The knee is the most common joint where osteosarcoma shows up. The knee joint involves the lower end of the femur (thigh bone) and the upper end of the tibia (lower leg bone). But osteosarcoma can also affect the humerus (upper arm bone), the pelvis, the spine, and the bones of the face and head.
Many times the patient just thinks he or she strained the arm or leg in sports or other recreational activities and waits for it to get better. But the pain doesn’t go away and after several weeks or months, it becomes constant, even waking the person up from sleep at night. If the bone weakens enough from the growing tumor, a fracture can occur and then the diagnosis is finally made. Late signs and symptoms also include weight loss, fatigue, and fever.
X-rays show fractures but don’t always show the full extent of bone tumors. MRIs help pinpoint how far the tumor has invaded into the soft tissues, nerves, blood vessels. They can show how much of the bone marrow has been replaced by the growing tumor. And the MRI helps show if there is metastases (spread) of the cancer. A surgeon will take a core sample of the tumor (called a biopsy) to make the final, specific diagnosis. The pathologist who looks at the sample under a microscope is able to identify the subtype.
Osteosarcoma has a less than optimal prognosis. This is partly caused by the fact that by the time the diagnosis is made, the tumor has spread in 20 per cent of all cases. And that refers to detectable metastases — meaning it can already be seen on imaging studies. Micrometastases (invisible or undetectable but very much present) are very likely present in most other patients. It’s just a matter of time before the tumors spread and grow enough to show up on a diagnostic test. Osteosarcoma spreads through the blood, first to the lungs and then to other bones.
Treatment is aimed at removing the primary (main) tumor and killing off any tumor cells that can’t be seen before they have time to grow. Before a specific treatment plan can be devised, the tumor must be staged. The physician relies on imaging studies (X-rays, MRIs, PET scans, bone scans) to stage the tumor from Grade I (low) to Grade IIB (high) and Grade III (low to high but with metastases already present).
Chemotherapy is often done before surgery to shrink the number of circulating tumor cells. This is important for patients with known metastases and because of the high risk of micrometastases already present. Chemotherapy also helps reduce the amount of blood supply to the tumor, which gives it a chance to shrink the main tumor as well. When chemotherapy has been completed, the body is given a three to four week rest in preparation for surgery. This sounds scary at first — you may think, what if the cancer cells start growing back during that break in time? But studies show no apparent bad effect of waiting in this fashion.
Surgery can be very complex and is meant to save as much of the normal anatomy as possible. This procedure is called limb salvage. Sometimes it just isn’t possible to save the leg or arm and amputation is necessary. Removing as much of the tumor and the metastatic lesions as is possible will improve the prognosis. The decision to have the limb cut off is never easy. But for some patients, by the time the surgeon removes the necessary tissue and begins to do plastic surgery to improve function and appearance, it’s just easier and more functional to have an amputation.
When limb salvage is the treatment direction, the surgeon is faced with many possible decisions, too. What’s the best way to reconstruct the joint? Joint replacement may be necessary to stabilize the limb while keeping as normal biomechanical function as possible. Joint stability is important, but for the growing child/teen, maintaining equal limb lengths is just as important. Specifically designed adjustable growth rods can be placed inside the bone.
Once the tumor has been surgically removed and the limb restored as close to normal as possible, then a second round of chemotherapy is started. The patient, family members, and health care team must now watch for complications from the surgery such as infection, poor wound healing, failure of any mechanical parts, and joint instability. The treatment team does everything it can to reduce the risk of limb loss and cancer recurrence. The results of a multidisciplinary approach to osteosarcoma with improved treatments have really improved survival and quality of life over the last 10 to 20 years.
It used to be that amputation was the only treatment option. Now with limb salvage procedures, that’s not always necessary. Survival rates have increased from 10 to 20 per cent back in the 1960s to almost 80 per cent today. That optimistic figure of 80 per cent applies to patients who don’t have any sign of metastases. The presence of mets changes the prognosis downward toward a shorter lifespan and increased risk of cancer recurrence.
Pre- and postoperative chemotherapy has helped improve results. It is hoped that with continued research, new and better drugs to target the cancer cells will be available in the near future. Right now, the relapse rate is 30 to 40 per cent within three years after treatment. If the cancer returns, the prognosis is not too good — less than two out of every 10 patients with recurrence of osteosarcoma will make it.
Even though that sounds grim, there is cause for optimism. Studies show that removing the new tumor can improve survival rates. Whether or not that patient should have another round of chemotherapy remains a question that is up in the air. One of the big research questions is what kind of chemotherapy (if any) works best for recurrence of osteosarcoma? Scientists believe it is only a matter of time before their efforts to find less toxic drugs that specifically target tumor cells will pay off. When that happens, we should expect to see improved survival rates with fewer limbs amputated and a better cosmetic result in the end.