Metastatic Bone Disease

Metastasis, or metastatic disease, is the spread of cancer from an initial or primary site in one organ or part of the body to a secondary non-adjacent organ or part.

Epidemiology

It is estimated that there are over 20,000 new cases of metastatic bone disease (MBD) in the UK each year.

Although any type of cancer can in theory spread to bone, MBD is most commonly seen in Breast, Prostate, Lung, Renal and Thyroid cancers.

In Breast and Prostate cancer in particular, the incidence of MBD is approximately 70% in advanced disease.

Presentation

The most common presenting feature is pain, usually exacerbated by weight-bearing and often worse at night.

Pathologic fracture occurs in about 20% of patients with MBD.

Patients may also present with symptoms of hypercalcaemia in about 20% of cases. Symptoms include generalised bone pain, nausea and vomiting, polyuria, abnormal heart rhythms, depression, cognitive dysfunction, and in extreme cases depressed consciousness.

Acute spinal cord or neural compression manifests in around 10% of patients, and bone marrow failure presenting as a pancytopaenia has been reported in up to 9% of patients with MBD.

Assessment 

Never assume that a solitary lesion is a metastasis!

A full medical history and examination must be performed and the general condition of the patient assessed.

Baseline blood tests, including a bone profile to look for hypercalcaemia, plasma electrophoresis to screen for myeloma, and tumour markers as indicated by the history and physical.

If the primary source of MBD is unknown, further investigations should be directed to finding it (CT chest/abdo/pelvis, mammogram, etc)

As a minimum, a full length radiograph of the affected bone must be obtained to rule out other lesions within the same bone. An isotope bone scan can help elicit other  sites of MBD, although it is often cold in myeloma.

If diagnostic doubt remains,  or the lesion is solitary, a biopsy is indicated. If done early, it can also help guide other investigations. Read more about the principles of how to biopsy a musculoskeletal tumour.

Assessing Fracture Risk

Mechanical or functional pain is a good indicator of imminent fracture risk, as are avulsion of the lesser trochanter, and >50% erosion through the cortex of a long bone on any view.

Mirels developed a scoring system to help rationalise the decision making process regarding the risk of pathological fracture and when to intervene with prophylactic fixation. The system has four categories scored 1-3, giving a maximum total of 12 points. Patients with scores of 8 and above are at high risk of fracture and should be considered for prophylactic fixation. The categories are:

  • Site: upper limb (1pt), lower limb (2pts), intertrochanteric (3pts).
  • Pain: mild (1pt), moderate (2pts), limits function (3pts).
  • Lesion: blastic (1pt), mixed (2pts), lytic (3pts).
  • Size: (maximal cortical destruction in any view) <1/3 (1pt), 1/3-2/3 (2pts), >2/3 (3pts).

Prognosis, pre-morbid functional status, and the likelihood that the lesion may respond to non-surgical treatment should also be taken into consideration.

Non-Surgical Treatment

Radiotherapy is usually palliative and is generally given in a single fraction. It may prevent a fracture from occurring  if the lesion subsequently heals.

Chemotherapy clearly has a role in chemo-sensitive tumours and should be discussed with oncologists in the setting of the MDT.

Bisphosphonates are a class of drug which block the mechanisms of bone resorption by stimulating apoptosis (programmed cell death) in osteoclasts, the cells which normally resorb bone. Their use is essential in cases of hypercalcaemia related to MBD. Critically, The addition of zoledronic acid to adjuvant endocrine therapy has been shown by Gnant et al to improve disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. You can read the paper by Gnant et al in the New England Journal of Medicine.

Prophylactic Fixation

Read more about the principles for surgical treatment of metastatic bone disease.

References

British Orthopaedic Association Guidance on Metastatic Bone Disease.

Mirels H. Metastatic Disease in long bones. A proposed Scoring System for diagnosing impending pathologic fracture. Clin Orthop Rel Res 1989: 249; 256-264

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Classification of soft tissue tumours

Soft tissue tumours are classified using the WHO classification, based on the morphological appearances of the tumour and whether or not it is benign or malignant. There are more than 50 variants of soft tissue sarcoma. The classification includes:

  • adipocytic tumours (eg lipoma, liposarcoma)
  • fibroblastic/myofibroblastic tumours (eg elastofibroma, adult fibrosarcoma)
  • so-called fibrohistiocytic tumours (eg GCT of tendon sheath, pleomorphic MFH)
  • smooth muscle tumours (eg angioleiomyoma, leiomyosarcoma)
  • pericytic tumours (eg glomus tumour)
  • skeletal muscle tumours (eg rahbdomyoma, rhabdomyosarcoma)
  • vascular tumours (eg haemangioma, angiosarcoma)
  • chondro-osseous tumours (eg soft tissue chondroma, extraskeletal osteosarcoma)
  • tumours of uncertain differentiation (eg intramuscular myxoma, synovial sarcoma)

Classification of primary bone tumours

Primary bone tumours can be classified according to the tissue of differentiation, using the WHO system. Tumours are classified as:

  • cartilage tumours (eg osteochondroma, chondrosarcoma)
  • osteogenic tumours (eg osteoid osteoma, osteosarcoma)
  • fibrogenic tumours (eg desmoplastic fibroma, fibrosarcoma)
  • fibrohistiocytic tumours (eg benign fibrous histiocytoma, malignant fibrous histiocytoma)
  • Ewing sarcoma/Primitive Neuroectodermal tumour (PNET)
  • Haemopoetic tumours (eg plasma cell myeloma)
  • Giant cell tumour of bone
  • Notochordal tumours (eg chordoma)
  • Vascular tumours (eg haemangioma)
  • Smooth muscle tumours (eg leiomyosarcoma)
  • Lipogenic tumours (eg lipoma, liposarcoma)
  • Neural tumours (eg neurilemmoma)
  • Miscellaneous tumours (eg adamantinoma)
  • Miscellaneous lesions (eg aneurysmal bone cyst)
  • Joint lesions (eg synovial chondromatosis)
For more information look here.
A simpler classification can also be helpful:
  • Cartilage forming tumours
  • Bone forming tumours
  • Fibrous tumours
  • Non-matrix producing tumours