What is Primary Bone Cancer?

Primary bone cancer is an uncommon type of cancer that starts in the bone cells. While it can occur anywhere in the body, it is very rare, making up only about 0.2% of all worldwide cancer cases. We often don’t know what causes these cancers. There are several types of primary bone cancer, with osteosarcoma, chondrosarcoma, and Ewing sarcoma being the most common. Each type affects different people, looks different in medical images, and has different behaviors.

These cancers are often aggressive, which means they can grow and spread quickly if not detected early. Diagnosis usually involves medical imaging, like an X-ray, and a biopsy where a small piece of the tumor is taken to be looked at under a microscope.

Once detected, surgery to remove the cancer is the main form of treatment. Other treatments like chemotherapy and radiation, which use powerful drugs or high-energy beams to kill cancer cells, are also used apart from surgery.

What Causes Primary Bone Cancer?

Even though the primary cause of bone cancer is often unknown, there are still certain risk factors that can contribute to its development.

Some people might have a genetic makeup that makes them more susceptible to developing bone cancer. This has a lot to do with genes that control how our cells grow and divide. For example, if there is a defect in the TP53 tumor suppressor gene, it can cause a condition called Li-Fraumeni syndrome, which can increase the individual’s risk for a type of bone cancer called osteosarcoma. Another gene, called the Rb1 gene, is connected to an eye cancer known as retinoblastoma but can also raise the risk of osteosarcoma if it is mutated. Additionally, certain conditions, like Werner and Rothmund-Thomson syndromes, are also associated with a higher chance of developing osteosarcoma.

If one has had radiation therapy as a cancer treatment in the past, especially as a child, this can increase the risk of developing bone cancer later on in life. This is particularly true when the treatment involved ionizing radiation.

There are also some non-cancerous (benign) conditions that can potentially become cancerous over time. For instance, Paget disease is a condition that disrupts the normal cycle of bone renewal and repair, making patients more likely to develop osteosarcoma, although it’s a rare complication. Also, growths called enchondromas and osteochondromas, which start in the cartilage (the smooth, rubbery connective tissue on the end of bones), have the potential to become a malignant type of cancer known as chondrosarcoma.

Risk Factors and Frequency for Primary Bone Cancer

Primary bone cancer is quite rare, accounting for only a small percentage of all types of cancer, including those in children. In 2020, roughly 3,600 new cases were reported in the United States, resulting in about 1,720 fatalities. Each type of primary bone cancer has a different prevalence among adults and children. The disease also appears to be slightly more common in males.

Primary bone cancer makes up 0.2% of all cancers and 5% of cancers in children.
In the United States in 2020, approximately 3,600 people were diagnosed, and 1,720 people died from it.
Among adults, chondrosarcoma is the most common form (40%), followed by osteosarcoma (28%).
For children and teenagers, osteosarcoma is the most common (56%), with Ewing sarcoma in second place (34%).
Other types of primary bone cancer include chordoma, undifferentiated pleomorphic sarcoma, adamantinoma, fibrosarcoma, and giant cell tumor of the bone, but these are less common.
The disease is slightly more common in males, with the global ratio of male to female osteosarcoma patients being 1.43 to 1.

Signs and Symptoms of Primary Bone Cancer

Primary bone cancer is an uncommon condition that many primary care doctors might never see in their patients. Despite its rarity, early detection of this cancer can greatly improve a patient’s chances of survival, but it’s frequently diagnosed late. Identifying bone cancer first requires considering the patient’s medical history and physical symptoms. If there’s a suspicion of bone cancer, the patient should be immediately referred to a specialist for a more detailed examination.

The most frequent symptom of bone cancer is deep, persistent pain that gets worse over time and doesn’t respond to basic pain relief medications. This pain can be especially bothersome during the night. Additionally, a patient might present a palpable lump with localized tenderness. Some patients may show general signs of illness, like tiredness, feeling unwell, or fever. However, the absence of these symptoms in cases of high-grade tumors could mean that the cancer has spread to other parts of the body. An abnormal fracture can sometimes be the first indication of bone cancer; therefore, any unusual fracture needs to be investigated further. Knowing if the patient has genetic conditions that increase the risk of bone cancer, like Li-Fraumeni syndrome, hereditary retinoblastoma, Werner syndrome, Rothmund-Thomson syndrome, or Paget disease, is vitally important.

During the physical examination, doctors should pay attention to the pain, tenderness or lump. They should closely examine the affected area, taking note of the size, firmness, mobility, and location of the mass and any changes to the skin on top of it. Any swollen lymph nodes should also be checked.

Testing for Primary Bone Cancer

To diagnose primary bone cancer, doctors usually rely on different methods such as imaging tests, laboratory blood tests, and tissue biopsy.

Fundamental to this process is the use of plain x-ray images. These images might show irregularities in your bone such as holes or dense spots. Sometimes the bone may have a ‘moth-eaten’ appearance, which suggests the bone destruction caused by a rapidly growing tumor. Other times, the disease might progress through the bone, creating an unclear boundary between the healthy and ill parts of the bone. Some tumors can partially lift off the bone which can look like an ‘onion skin,’ while others create a sharp ‘triangle’ or a starburst pattern of bone changes.

Another useful tool for identifying the local extent of your tumor is an MRI scan. It manages to capture images of bones and soft tissues that give detailed insights about the tumor. Using the latest techniques, we can even identify the high-risk areas of the tumor and see how your tumor is reacting to chemotherapy.

A CT scan is important if the diagnosis is unclear after the MRI scan or if an MRI isn’t suitable for you. It’s particularly useful in the diagnosis of pelvic bone cancer and is often utilized when planning reconstructive surgery. If you’re diagnosed with primary bone cancer, a chest CT scan will usually be done to look for any signs of spread (metastases).

A whole-body bone scan is a special type of imaging test that uses a small amount of radioactive material to highlight areas of bone change. These scans help in detecting any cancer spread. PET scans might also be used for initial cancer staging and follow-up. This scan helps to detect the high metabolic activity in abnormal cells, which is typical of cancer.

Blood tests alone can’t diagnose bone cancer but they can give some useful information about your general health and how well your kidneys and liver are working—useful to know if chemotherapy is being considered. Certain blood markers, like alkaline phosphatase and lactate dehydrogenase, can provide some indication about the cancer, and are often followed over time to assess for any recurrence of the disease.

A biopsy of the suspicious area is necessary to confirm the diagnosis of bone cancer. This procedure will provide a small tissue sample which will be examined under a microscope by a specialist bone cancer pathologist. It will tell us about the type and grade of cancer cells present. Biopsies can be guided by ultrasound, x-ray, or CT, and it’s important that the approach is carefully planned. Incorrectly done biopsy can affect future treatment options.

Treatment Options for Primary Bone Cancer

Managing primary bone cancer requires team effort from specialists in a bone cancer center. This includes professionals who are specifically trained in working with kids or teenagers. Treatment varies based on several factors such as the type of bone tumor, the grade and the stage of cancer, and your preference. Surgically removing the tumor is the main method for treating primary bone cancer. Other widely used treatments include chemotherapy before and after the surgery, and radiation therapy which is used in some cases.

Let’s take a look at the various treatment approaches:

Surgery

The goal of surgical removal is to completely remove the tumor while keeping as much functionality in the affected limb as possible. The decision on whether to try to salvage the limb or to amputate it relies on several factors, including imaging results, pathology reports, the response to post-surgery treatment, and your preference. Surgery can often lead to significant loss of tissue and it’s important that you understand the potential pros, cons and long-term functional impact of the surgery. Low-grade tumors that can be removed with surgery usually require wide excision, i.e, removing the part of the bone affected by the tumor along with some healthy tissue around it. High-grade tumors may require radical excision which means removing the affected bone and nearby soft tissues within the same anatomical area.

Chemotherapy

Use of multiple chemotherapy drugs is common in managing primary bone cancer. Usually, this involves chemotherapy before surgery (neoadjuvant) and chemotherapy after surgery (adjuvant). These have improved the rates of limb-saving surgery and overall survival. Chemotherapy is part of the standard treatment for bone cancers like Osteosarcoma and Ewing’s sarcoma. Chondrosarcoma is mainly managed with surgery, although in some cases, chemotherapy and radiotherapy are used.

Neoadjuvant chemotherapy primarily aims to reduce the risk of cancer spreading in future; however, studies also suggest it can help control the primary tumor. If a patient has positive responses to such chemotherapy, that suggests less histological necrosis (cell death), which in turn might signal need to alter post-surgery chemotherapy and suggest a less favorable prognosis.

Radiotherapy

Radiation therapy, or radiotherapy, is also often used to treat primary bone cancer. It’s commonly used to treat Ewing’s sarcoma since this type of tumor responds well to radiation. Sometimes, radiotherapy is given before surgery if the tumor didn’t respond well to chemotherapy before surgery or if the tumor is in a hard-to-reach area where reducing the tumor size will aid in surgical removal. If a large portion of the tumor can’t be removed surgically or doing so would cause significant disability, radiotherapy is used for local treatment. If not all of the tumor can be removed during surgery, postoperative radiotherapy is conducted. Chondrosarcomas are less responsive to radiotherapy, in these cases radiotherapy is only used for tumors that can’t be surgically removed or were not completely removed. Radiotherapy also helps relieve pain and slow down the growth of all primary bone cancers.

When diagnosing primary bone cancer, other conditions and types of tumors need to be considered. These may include:

Malignant Tumors:

Metastases – cancer that has spread from another part of the body
Lymphoma – cancer affecting the lymphatic system
Multiple myeloma – a type of blood cancer

Benign Tumors:

Giant cell tumor – a rare, usually non-cancerous tumor
Osteoblastoma – a rare bone tumor, usually benign
Enchondroma – a non-cancerous bone tumor
Chondromyxoid fibroma – a rare, benign bone tumor
Cortical desmoid – typically a benign bone tumor

Infections:

Osteomyelitis – infection in the bone

Trauma:

Fracture callus – a bump that forms as a bone heals

Other Conditions:

Aneurysmal bone cyst – a non-cancerous bone tumor filled with fluid
Fibrous dysplasia – a bone disorder where normal bone is replaced with fibrous tissue

What to expect with Primary Bone Cancer

The outlook for primary bone cancer depends on many factors. Unfortunately, the 5-year survival rate hasn’t improved much over the last 25 years. In the United States, statistics from the National Cancer Institute show that about 66% of patients survive five years after diagnosis, although rates might be lower in the United Kingdom.

For those patients where the disease is only in the bone where it started, called localized osteosarcoma, 60 to 78% still live 10 years after diagnosis. However, for those patients who already have cancer spread to other parts of their body at diagnosis, the survival rates drop to between 20% to 30%. The likelihood of survival is reduced by factors such as having the tumor in the middle or near part of a limb, having larger tumors, high levels of certain substances in the blood (like alkaline phosphatase or lactase dehydrogenase), being older, experiencing a break in the bone caused by the cancer, and no significant improvement after initial chemotherapy.

For a type of bone cancer known as chondrosarcoma, the most important factor affecting survival is the grade of the cancer – a measure of how much the cancer cells resemble normal cells. Other factors affecting survival include having the cancer already moved to other parts of the body when diagnosed, older age, and having the cancer located in the pelvis. Those with low-grade chondrosarcoma have a 83% chance of surviving for 5 years, dropping to 53% for those with higher grades.

Ewing sarcoma, another type of bone cancer, also has a different survival rate depending on whether the disease is localized or not. When the disease is localized, 70% to 80% of patients survive at least 5 years post-diagnosis. If the cancer has only spread to the lungs, the survival rate drops to 50%. If it has spread to any other part of the body, less than 30% of patients survive 5 years. Factors that make the survival rate worse include having the tumor in the pelvis, larger tumor size, and lack of significant improvement after either initial or subsequent chemotherapy treatment.

Possible Complications When Diagnosed with Primary Bone Cancer

The complications resulting from primary bone cancer can be varied and are broken down into two categories:

Complications related to the tumor itself:

Pathological fracture
Return of the tumor
Cancer spreading to other parts of the body

Complications related to the treatment, which could be:

Surgery
- Infections at the surgical site or around the prosthetic
- Failure of the surgical implant
- Non-healing or fracture of the biological implant
Chemotherapy
- Short-term side effects like feeling unwell, anemia, nausea, vomiting, and hair loss
- Long-term side effects like heart and kidney damage, hearing loss, and an increased risk of developing another cancer
Radiotherapy
- Side effects can vary depending on the treatment area, causing damage to the skin, organs in the pelvic area, digestive system, and lungs
- There is also a small increase in the long-term risk of developing another cancer