The three most common primary cancers of bones and joints are osteosarcoma, Ewing sarcoma, and chondrosarcoma. Of the three, chondrosarcoma has the best prognosis. The ages at which these cancers most often occur vary. Osteosarcoma, a malignant bone tissue tumor commonly found near the growing end of the long bones, is the most common, and occurs most frequently in teens and young adults. Ewing sarcoma, a tumor often located in the shaft of long bones and in the pelvic bones, occurs most frequently in children and youth. Chondrosarcoma, a sarcoma of malignant cartilage cells, often occurs as the result of malignant degeneration of pre-existing cartilage cells within bone, including chondromas (a benign tumor), and is primarily found among older adults. However, the vast majority of chondromas never undergo malignant change; therefore, the routine resection of benign chondromas is unwarranted.
Of these three, Ewing sarcoma is generally considered to have the worst prognosis, followed by osteosarcoma. However, this perception is largely due to the greater tendency for osteosarcomas to present as high-grade tumors and for chondrosarcomas to present as low-grade tumors. When analyzed by stage, a recent survivorship analysis revealed similar survivorship rates for low-grade chondrosarcoma compared to low-grade osteosarcoma, and similar survivorship rates for high-grade chondrosarcoma when compared to high grade osteosarcoma. By definition, all cases of Ewing sarcoma are high-grade, the most aggressive category of cancer, with full potential to metastasize and bring about death. Approximately 6% to 20% of osteosarcomas are of lower grade; chondrosarcoma has a higher proportion of low-grade cases than these other two bone and joint cancers.
The fourth common “primary” cancer of the bone is myeloma, a malignant primary tumor of the bone marrow formed from a type of bone marrow cells called plasma cells (the cells that manufacture antibodies). This cancer and usually involves multiple bones simultaneously. The isolated single-bone version of myeloma is called plasmacytoma, but virtually all cases of isolated plasmacytoma evolve into full-fledged multiple myeloma within 5 to 10 years after diagnosis of the plasmacytoma. Like leukemia and lymphoma, myeloma is more properly considered a primary cancer of the hematopoietic bone marrow. Unlike leukemia, however, myeloma typically causes extensive changes or damage to the bone structure itself, causing fractures, pain, and hypercalcemia. Because of the associated bone destruction, myeloma is generally included in analysis of bone cancers; however, leukemia and lymphomas generally are not considered primary bone cancers, presumably because of the lower likelihood of structural bone destruction and associated complications. Non-Hodgkin’s lymphomas, however, warrant some consideration due to the frequency of bone destruction and pathological fractures requiring operative intervention.
SEER estimated that in 2013, 3,010 people were newly diagnosed with cancer of the bones and joints. The number of new cases of bone and joint cancers is 0.9 per 100,000 people per year. In addition, 1,440 people will die annually from cancer of the bone and joints.1 According to SEER statistics, the rates for new bone and joint cancer cases have been rising, on average, 0.4% each year over the last ten years. However, death rates have fallen on average 0.3% per year, with survival rates rising slightly. Incidence estimates derived from NCDB are slightly higher without an appreciable change in survival. There has been a gradual increase in the number of cases reported to the NCDB in the past 13 years. While the reason for this difference is unknown, it could reflect reporting changes rather than incidence changes.
Myeloma occurs five to six times as frequently as the other bone cancers. It will be diagnosed in 22,350 persons per year, an incidence rate of 5.9 per 100,000 persons per year. An expected 10,710 persons died of myeloma in 2013.2
Although annual cases included in the American College of Surgeons National Cancer Data Base (NCDB) show a slower rate of increase, proportionately, for bone and joint cancers than for cancer cases overall, the incidence of bone and joint cancers is increasing. Between 2000 and 2011, the annualized number of primary cases recorded increased by nearly 15%. Myeloma cases, however, increased at twice the rate of cancer cases overall, 47% to 23%, respectively. (Reference Table 8A.5.2 PDF [1] CSV [2])
Gender and Race
Bone cancers and soft tissue sarcomas are found more frequently in males than females, and more frequently among Whites than those of any other race. However, rates have varied slightly for both genders and by race for the past decade. The average annual incidence of bone cancers between 2006 and 2010 was nine in one million, a rate that has remained constant for the last decade. The rate among White males was 12 in one million, while, among White females it was eight in one million. The lowest rate of six in one million was found for both males and females of the Asian or Pacific Islander race. The incidence of cancer of the bones and joints in the United States is comparable to several site-specific oral cancers (ie, lip, salivary gland, floor of the mouth), cancers of the bile duct, cancers of the eye, and Kaposi’s sarcoma, which affects the skin and mucous membranes and is often associated with immunodeficient individuals with AIDS. (Reference Table 8A.1.1 PDF [5] CSV [6])
As with bone and joint cancers, males have a higher incidence of myeloma than do females, with an average of 71 cases in one million males to 42 cases in one million females. Blacks have a much higher incidence rate of myeloma than Whites. The incidence of myeloma in the United States is comparable to the incidence of esophageal, liver, cervical, ovarian, brain, and lymphocytic leukemia cancers. (Reference Table 8A.1.2 PDF [7] CSV [8])
Age
The median age for cancers of the bones and joints has risen slightly, to age 42 years, in recent years. However, it remains the leading cause of cancer in young persons under the age of 20 years. More than one in four diagnoses of bone and joints cancer is in children and youth under the age of 20 years, with more than one-half (52%) of cases diagnosed in person younger than 45 years. Males are typically diagnosed with bone cancers, and die from bone cancer, at an age several years younger than females. (Reference Table 8A.2.1 PDF [9] CSV [10] and Table 8A.3.2 PDF [11] CSV [12])
Myeloma, on the other hand, is primarily a cancer found among elderly persons, with a median age of 69 at the time of diagnosis. Eight-five percent of new myeloma cases are diagnosed in persons age 55 years and older. Again, males are typically diagnosed with myeloma at ages several years younger than females. (Reference Table 8A.2.1 PDF [9] CSV [10], Table 8A.2.2 PDF [13] CSV [14], and Table 8A.3.2 PDF [11] CSV [12])
Death from bone and joint cancer, at a median age of 59 years, occurs at a younger age than any other type of cancer. (Reference Table 8A.2.2 PDF [13] CSV [14])
Annual population-based mortality rates due to cancers of bones and joints are low, averaging four deaths per one million people since the early 1990s.1 While the mortality rate from bone and joint cancer dropped by approximately 50% from that of the late 1970s, no significant improvement in this rate has been observed over the past 20 years.2 Males have a higher mortality rate than females for all races. (Reference Table 8A.4.3 PDF [15] CSV [16])
The overall 5-year survival rate in 2006–2010 for bone and joint cancers was 66%, placing it roughly in the middle of all cancers for 5-year survival and comparable to a number of more common cancers such as non-Hodgkin lymphoma, urinary, cervical/ovarian, and soft tissue cancers. This is an increase of 14% since 1975, when the 5-year survival rate was 52%. The median number of years of survival after diagnosis is 17, with males averaging 16 years and females 18 years.
The overall 5-year survival rate for the primary types of bone and joint cancers is 54% for osteosarcoma, 75% for chondrosarcoma, and 51% for Ewing sarcoma. The osteosarcoma survival rate varies with age: The 5-year survival was 70% for children and youth under the age of 20 years,3 60% for people under 30 years of age, 50% for those aged 30 years to 49 years, and 30% for those 50 years old and older.2 If Ewing sarcoma is found before it metastasizes, the 5-year survival rate for children and youth is about 70%. However, if already metastasized when found, the 5-year survival rate drops to 15% to 30%.4 (Reference Table 8A.4.1 PDF [17] CSV [18], Table 8A.4.2 PDF [19] CSV, [20] and Table 8A.4.3 PDF [15] CSV [16])
The annual population-based mortality rate of myeloma was an average of 34 persons per one million population between 2006 and 2010.5 The mortality rate from myeloma has remained relatively constant since the mid-1970s. The 5-year survival rate for myeloma, 43%, is one of the lowest for all cancers; however, due to being primarily a cancer of older persons, this age-relatedness may well affect survival regardless of the presence or absence of myeloma. The median survival after diagnosis of myeloma is only 6 years. (Reference Table 8A.4.1 PDF [17] CSV [18], Table 8A.4.2 PDF [19] CSV, [20] and Table 8A.4.3 PDF [15] CSV [16])
Within the NCDB, no change in the overall survival rates for patients diagnosed and treated in the years 1985 to 1988 compared to patients between 1994 and 1998 was found. There have been no substantial changes in therapies utilized for osteosarcoma since 1998 and the overall 1998–2010 NCDB data reveals no significant improvement, with an approximate 50% five-year overall survival. However, the survival rate varies greatly with the histologic subtype of sarcoma. For instance, the 5-year relative survival rate is 53% for classic high-grade osteosarcoma, 87% for parosteal osteosarcoma and 18% for osteosarcoma associated with Paget's disease of the bone. (Reference Table 8A.8.1 PDF [21] CSV [22])
The economic burden of bone cancers can be great. The more advanced the disease, the worse the prognosis and, accordingly, the more expensive the treatments. It is likely that early detection, and, certainly, prevention if possible, could drastically reduce costs. A number of expensive treatments are required to address these tumors. In the 2007 report by Damron, Ward, and Stewart,1 it was noted that the most frequent initial treatments varied widely based on the type of sarcoma. Although not reported, these treatments vary widely based on the stage of the disease as well.
Collectively, they reported that surgery alone was the most common initial treatment for chondrosarcomas (69%), whereas for Ewing sarcoma, treatments were divided between surgery and chemotherapy (24% of cases), radiation and chemotherapy (23%), and chemotherapy alone in 18%. With osteosarcoma, when initial treatment was known, the largest group received surgery and chemotherapy (46%). Surgery was reported as part of the initial treatment in 71% of osteosarcoma patients, 83% of chondrosarcoma patients, and 47% of Ewing sarcoma patients. The most frequent operations performed were limb-sparing radical resections and excisions. When the type of surgery was defined and known, limb-preservation surgery was performed in 69% of osteosarcomas, 79% of chondrosarcomas, and 81% of Ewing sarcomas.1
Radiation therapy was employed in 10% of osteosarcomas, 14% of chondrosarcomas, and 46% of Ewing sarcoma cases. In Dr. Ward’s personal series of more than 100 osteosarcomas, amputation has been required in only 17% of patient, but almost all patients have had surgical resection, limb reconstruction, and chemotherapy.1
Multiple therapies may be needed later in the course of the patient’s disease, especially in the more advanced cases. In later stages of the disease for those not cured with surgery alone, significant costs will accumulate as the patients develop pulmonary disease and, ultimately, die. Hormone therapy, immunotherapy, and bone marrow transplant/endocrine treatments each accounted for 1% or less of initial treatments. However, in severely affected individuals in whom standard treatments fail, these alternative treatments may be tried more frequently. Currently, the authors are not aware of any data source that reports the rate of utilization of such late treatments.
All of these treatments are costly to administer. Per-patient cost will vary widely depending on the treatments utilized, and the number and intensity of treatments. Over all, treatment for bone and joint cancers can easily exceed $100,000 for a single patient. This is particularly true if that patient receives surgery, chemotherapy, and radiation therapy. If one includes the cost of bone-replacing endoprostheses or the costs of artificial limbs used in those cases that required amputations, the cost will be much higher. In addition to the direct medical cost, there are extensive indirect and social costs from lost work time and disability. For some patients, healthcare costs associated with their bone and joint cancers will be ongoing.
The burden of paying the cost of treatment for bone and joint cancers is shifting. In the study cited above, from 1998 to 2010, managed care provided insurance coverage for the largest portion of patients (37%), following by Medicare with supplement (16%). Medicare and Medicaid were roughly equal at 8% and 8%, respectively. However, analysis of the NCDB insurance data available for 1,738 (95.7%) of 1,816 bone and joint cancer cases reported for 2010 show Medicare and Medicaid covering a much larger share.
Almost all cancers have preferential sites to which they spread or metastasize, resulting in secondary cancers. Secondary bone cancer is much more common than primary bone cancers, and result in great morbidity and pain. The three most common sites of cancer metastasis are lung, liver, and bone. The skeleton is the most common organ affected by metastatic cancer, and the site of disease that produces the greatest morbidity. The most commonly encountered cancers that readily and frequently spread to bone are cancers of the breast, lung, kidney, prostate, gastrointestinal tract, and thyroid gland. The incidence of bone metastases in lung cancer patients is approximately 30% to 40%, and the median survival time (MST) of patients with such metastases is 6 to 7 months.1 At postmortem examination, 70% of patients dying of breast and prostate cancer have evidence of metastatic bone disease. Cancers of the thyroid, kidney, and bronchus also commonly give rise to bone metastases, with an incidence at postmortem examination of 30% to 40%.2 Brain and ovarian cancers rarely spread to bone. Many other cancers have intermediate rates of spread to bones.
A tumor formed by metastatic cancer cells is called a metastatic tumor or a metastasis. The cancer cells in their new metastatic site closely resemble the original or primary cancer from which the cancer initially arose. For example, breast cancer that spreads to the bone and forms a metastatic tumor is still considered metastatic breast cancer, not true bone cancer. It will still look like breast tissue and breast cancer when it is inspected or viewed under a microscope. Many lay people will now refer to it as bone cancer, but to the physician, bone cancer implies a cancer that started or originated in the bone, such as osteosarcoma, Ewing sarcoma, or myeloma, as discussed above.
Metastatic bone disease complications are termed skeletal-related events (SREs). SREs include pain, pathologic fracture, vertebral deformity and collapse, spinal cord compression, and hypercalcemia (overabundance of calcium in the blood) of malignancy. These complications result in impaired mobility and reduced quality of life (QOL) and have a significant negative impact on survival.2 In addition, metastatic disease may remain confined to the skeleton, with the decline in quality of life and eventual death almost entirely due to skeletal complications and their treatment.
The prognosis of metastatic bone disease is dependent on the primary site, with breast and prostate cancers associated with a survival measured in years compared with lung cancer, where the average survival is only a matter of months. Survival rates for secondary bone cancer depend on patient factors such as age, overall health, treatment, and response to treatment. However, due to the advanced stage of cancer that has spread, survival rates are much lower than for primary cancer without such spread.
The fundamental treatment for bone metastasis from advanced cancer is disease control by systemic chemotherapy and radiation of the bone lesions. Prevention and treatment of bone metastases is highly dependent on an effective treatment being employed against the primary cancer. As a direct treatment for bone metastases themselves, radiation therapy, surgery, and bisphosphonates are the mainstays of treatment. Intravenous bisphosphonates, such as zoledronic acid have been shown to prevent or reduce pathologic fractures and may reduce these costs.3 With FDA approval of the use of bisphosphonate medications to prevent such fractures in 1995, the incidence of fractures in treated patients has significantly decreased. The fracture rates reported in cases of metastatic disease and myeloma have been demonstrated in multiple studies to markedly diminish (roughly a 50% reduction in fracture rates in many studies). Although the tumors still metastasize to the bone, the associated bone destruction and consequent pathologic fracture rate is markedly less. The bisphosphonate medications work by interrupting a biochemical pathway required for bone breakdown by osteoclasts, the cells that normally remove bone in the process of bone remodeling. This bone breakdown step is overactivated in the presence of bony metastases, causing bone loss, bone destruction, and ultimately fractures from the weakening of the bone. Thus, the introduction of bisphosphonate medication has been a major advance over the past 20 years, one that had significant impact on the health of those with myeloma and metastatic cancer to the bone by preventing bone destruction, and thereby preventing bone weakening and subsequent fractures.
The economic burden of SREs in patients with bone metastases is substantial. A recent study showed that the estimated lifetime SRE-related cost per patient suffering from metastatic lung cancer was $11,979 USD, and that radiotherapy accounted for the greatest proportion of cost (61%) by SRE type.1 Finding cures and effective treatments for all types of cancer can help reduce the prevalence and costs associated with bone and joint cancer.
Overall cancers metastatic to bone cause significant pain and morbidity—approximately 50% of patients with metastatic cancer of lung, breast, prostate, and kidney develop bony metastases prior to death. Untreated, these metastases can lead to pathological fractures and cause great pain and disability. Thus, the elucidation of the biochemical steps involved in bone destruction and the development of drugs to combat such steps, have been an example of tremendous scientific advancement and achievement in the field of cancer research and treatment.
Links:
[1] https://www.boneandjointburden.org/docs/T8A.5.2.pdf
[2] https://www.boneandjointburden.org/docs/T8A.5.2.csv
[3] http://seer.cancer.gov/statfacts/html/bones.html
[4] http://seer.cancer.gov/statfacts/html/mulmy.html
[5] https://www.boneandjointburden.org/docs/T8A.1.1.pdf
[6] https://www.boneandjointburden.org/docs/T8A.1.1.csv
[7] https://www.boneandjointburden.org/docs/T8A.1.2.pdf
[8] https://www.boneandjointburden.org/docs/T8A.1.2.csv
[9] https://www.boneandjointburden.org/docs/T8A.2.1.pdf
[10] https://www.boneandjointburden.org/docs/T8A.2.1.csv
[11] https://www.boneandjointburden.org/docs/T8A.3.2.pdf
[12] https://www.boneandjointburden.org/docs/T8A.3.2.csv
[13] https://www.boneandjointburden.org/docs/T8A.2.2.pdf
[14] https://www.boneandjointburden.org/docs/T8A.2.2.csv
[15] https://www.boneandjointburden.org/docs/T8A.4.3.pdf
[16] https://www.boneandjointburden.org/docs/T8A.4.3.csv
[17] https://www.boneandjointburden.org/docs/T8A.4.1.pdf
[18] https://www.boneandjointburden.org/docs/T8A.4.1.csv
[19] https://www.boneandjointburden.org/docs/T8A.4.2.pdf
[20] https://www.boneandjointburden.org/docs/T8A.4.2.csv
[21] https://www.boneandjointburden.org/docs/T8A.8.1.pdf
[22] https://www.boneandjointburden.org/docs/T8A.8.1.csv
[23] http://www.cancer.net/cancer-types/osteosarcoma-childhood/statistics
[24] http://www.cancer.net/cancer-types/ewing-sarcoma-childhood/statistics
[25] http://seer.cancer.gov/statfacts/more.html.