Diagnosis and referral of adults with suspected bony metastasesBMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n98 (Published 25 January 2021) Cite this as: BMJ 2021;372:n98
- Samantha Downie, orthopaedic clinical research fellow1,
- Elizabeth Bryden, general practitioner2,
- Fergus Perks, consultant radiologist3,
- A Hamish RW Simpson, professor of orthopaedics and trauma1
- 1University of Edinburgh, Edinburgh, UK
- 2NHS Greater Glasgow & Clyde, Glasgow, UK
- 3NHS Lothian, Edinburgh, UK
- Correspondence to S Downie
What you need to know
Red flag symptoms for cancer related bone pain include severe progressive pain that is worse on movement or at night, inability to bear weight, signs of hypercalcaemia, and pain on direct palpation
Metastases may not show up on radiographs until 50-70% of the bone has been destroyed, so initial radiographs may be normal
Mirels’ score can be used to predict risk of fracture based on metastasis location, size, radiographic appearance, and pain
Prophylactic fixation (before a pathological fracture occurs) leads to better outcomes in terms of pain relief, hospital stay, and function
Surgery can relieve pain, improve function, and maximise independence, and is usually of benefit even if prognosis is poor
Of the 44 million people worldwide who are living with treated cancer, 30-80% will experience bone metastases.12345 Metastatic bone disease (MBD) can lead to pain, loss of function, and pathological (low energy) fractures.67
Patients can present to any specialty, and half of those with a first recurrence present to primary care.8 Initial diagnosis can be difficult as lesions may not be visible on radiographs until 50-70% of bone has been destroyed.9 Early treatment can reduce the need for surgery and improve outcomes101112; therefore, a high degree of suspicion is essential when assessing cancer patients with new bone pain.
Despite evidence that outcomes are better when we operate to stabilise bony lesions before they break, more than half of patients are not referred for surgery until they have sustained a pathological fracture.41314
Guidelines from the British Orthopaedic Oncology Society for good practice in metastatic bone disease were published in 201512 and called for targeted guidance for oncology and primary care to ensure that patients who could benefit from surgery were referred to their local centre early. These guidelines have not translated to a change in referral practice and clear guidance is needed for healthcare staff who care for patients with bone metastases.
This article, aimed at primary care and hospital doctors, covers assessment, investigation, and referral for patients with a history of cancer presenting with a suspected new bony metastasis.
How should I assess bone pain in patients with cancer?
Suspect bone metastases in patients with previous cancer and new musculoskeletal pain.11 All cancers (including haematological malignancies—eg, lymphoma) can metastasise to bone.3 The risk of bony secondaries is higher in those with metastases elsewhere (eg, viscera or lung).15 The five commonest sites for bone metastases are the vertebrae, pelvis, ribs, femurs, and skull, but metastases can occur in any bone.461016
Bone metastases present with progressive pain, which can interfere with activities of daily living.41617 Persistent background pain may be exacerbated by movement in an “episodic” pattern.418 Pain that is worse at night or aggravated by movement or weight bearing can indicate an impending fracture.161920
Patients may experience symptoms of hypercalcaemia, including nausea/vomiting, anorexia, constipation, muscle weakness, polyuria, and confusion.16 Vertebral metastases can cause neurological abnormalities that result from spinal nerve root involvement.4 Metastatic spinal cord compression (severe back or abdominal pain with associated sensorimotor deficits and/or features of cauda equina syndrome) is an emergency and merits urgent referral to oncology for a same day magnetic resonance imaging (MRI) scan.212223 In patients with severe back pain and known history of cancer, suspect metastatic spinal cord compression until it is ruled out.22 In areas of the body less commonly affected by bone metastases such as the skull, presentation may include localised pain with or without features of local nerve impingement—eg, facial palsy.24
Suspicious features on examination include pain on palpation, painful movement, or pain on weight bearing.161825 Alternatively, a reduced range of motion in the joint above or below the affected area may point towards an alternative pathology such as infection or gout. A targeted neurological exam focusing on any loss of motor power, sensation, or symptoms of peripheral nerve impingement is important. Clinical suspicion is based on loss of function, progression of symptoms, and associated features (fig 1).
What tests should be organised?
Figure 2 details an assessment pathway for patients with new bony pain based on the degree of suspicion of metastatic disease. Where suspicion is moderate or high, perform baseline blood tests, including full blood count, urea and electrolytes, bone profile (including corrected calcium and alkaline phosphatase), albumin, and any relevant tumour markers (eg, prostate specific antigen, cancer antigen 15-3, and carcinoembryonic antigen).1126 Seek urgent specialist input for patients with moderate to severe hypercalcaemia (>3 mmol/L); inpatient management is often required.
Low clinical suspicion
Initial investigation of patients considered to be at low risk is based on symptom duration and comprises modification of activity and interim review after two weeks.2728 Review patients sooner if symptoms progress.
Moderate or high clinical suspicion
If suspicion is moderate or high, request urgent radiographs (anteroposterior and lateral of entire affected bone). Radiographs can determine tumour size, cortical involvement, and detect the presence of multiple lesions (fig 3a).19 Bone metastases may not show up on radiographs until 50-70% of the cortical bone is lost (fig 3b), so initial radiographs may be normal.9 If radiographs are unremarkable but suspicion remains high, particularly if symptoms do not resolve or progress, further imaging may be necessary. A whole bone MRI is the most sensitive modality for identifying occult metastases (fig 3c).491213 Computed tomography imaging is also acceptable if MRI availability is limited or the patient has contraindications to MRI.
Which features indicate a high risk of fracture?
Radiographic features indicating an impending fracture include significant cortical destruction (more than 50% cortical destruction in any long bone or 50% circumferential involvement on an axial “cross-sectional” view).2930 Mirels’ score, first published in 1989, is the most commonly used method for assessing risk of pathological fracture (table 1).32 Despite some concerns that it may lead to over-treatment of lesions that will not go on to fracture, it is a useful tool for triaging patients.30 Urgently refer patients with lesions scoring 9 or more out of 12 to orthopaedics for counselling regarding surgery to prevent fracture (prophylactic fixation).12
Where should I refer patients with new bony metastases?
Refer patients with confirmed asymptomatic lesions or those at low risk of fracture to their cancer team for consideration of targeted or systemic medical management to prevent progression to fracture. Patients with substantial pain or lesions at high risk of fracture should be referred to the local trauma or orthopaedic oncology service who will liaise with the patient’s oncology team in planning surgical treatment.
Which specialist teams should be involved?
Any patient with a new bone metastasis diagnosis should be referred to their oncologist or appropriate multidisciplinary team.33 Management of MBD should be multidisciplinary, with oncology input to advise on benefit from radiotherapy and bone-modifying agents (eg, bisphosphonates and denosumab).41114 Radiotherapy to metastases can provide pain relief and improve function for 60% of recipients within 2-3 weeks.1734
Early involvement of multidisciplinary cancer teams including specialist nurses can expedite referrals to other specialties (including orthopaedics and radiology) and signpost patients to other sources of support, including physiotherapy, occupational therapy, counselling, and financial services.113335 Recent international consensus guidelines recommend the following criteria for palliative care referral: treatment resistant symptoms, assistance with decision making/advance planning, delirium and progressive disease despite optimal input from other specialties.3637
What can surgery offer?
In most cases, surgery for bone metastases is not curative.3839 The aims of treatment are to prolong survival, improve quality of life, relieve pain, and prevent complications such as fractures.14 Guidelines emphasise that surgical procedures are chosen to balance life expectancy with the necessary recovery time.440 Patients are counselled about the options for prophylactic versus reactive fixation (surgery to treat a fracture that has already occurred).41 Prophylactic surgery can prevent painful fractures but may be undertaken unnecessarily if the lesion does not fracture. However, reactive fixation can be more difficult technically to undertake, and may lead to a poorer outcome in terms of patient quality of life.3041 Studies comparing prophylactic and reactive metastatic lesion fixation are retrospective in nature with no randomised controlled trials available; however, cohorts are of moderate-large size with adequate follow-up, given the poor survival in this patient group.4243 The principles of orthopaedic management are summarised in box 1.
General aims in orthopaedic management of metastatic bone disease
Establish diagnosis (exclude a primary bone tumour, which may be curable) before deciding on type of surgery
Initiating non-surgical treatment (eg, bisphosphonates or radiotherapy) early can reduce the risk of requiring surgery or reduce the complexity of surgery46
Reduce pathological fracture rate by offering prophylactic fixation for lesions that are symptomatic/at risk of fracture. Prophylactic fixation reduces perioperative pain, length of hospital stay, and technical difficulty of surgical procedure4347
Evidence based patient counselling to enhance shared decision making in a palliative condition where enhancing quality of life to maintain function and independence is key
Patients who do not want surgery are unlikely to benefit from orthopaedic referral, but may benefit from input by orthotics or plaster room technicians for custom splints and orthoses that may improve the function in their affected limb. In addition, oncology input may highlight non-surgical options for their symptoms.1117 The focus for surgery in bone metastases should be on shared decision making in accordance with patient preference for palliation of symptoms.
Patients with advanced disease
Irrespective of prognosis, symptomatic metastases are usually treated with surgery as a palliative procedure. In frail patients with a short prognosis (1-6 months), prophylactic “damage control” surgery (eg, with an intramedullary nail or plate, fig 4a, 4b) can prevent fracture, relieve pain, and improve likelihood of discharge to the patient’s own home.42434748 Patients most likely to benefit from this approach include those with multiple metastases, an expected survival of 1-6 months,1249 or symptoms such as severe pain or difficulty mobilising.13 Observational studies of patient reported outcomes in surgery for bony metastases show sustained improvements in function and pain relief up to one year post surgery, and complication rates comparable with the older adult trauma patient population.405051
Patients with limited disease
In patients with low volume oligometastatic disease (<5 metastases throughout the body), studies indicate an enhanced survival and/or chance of cure with surgery.384452 Such patients may benefit from direct referral to orthopaedic oncology1247 and urgent staging investigations (computed tomography imaging of the chest, abdomen, or pelvis, and bone scan).19 Patients with a solitary suspicious bone lesion should undergo further imaging and/or biopsy before any surgical treatment to confirm whether the lesion is a metastasis or a new primary tumour.412
In patients who choose to have surgery, planned prophylactic fixation without major excisional surgery (eg, stabilisation with an intramedullary nail) can lead to better outcomes in terms of pain relief, hospital stay, and function.142653 In all cases, timely diagnosis of bony metastases and targeted medical management (eg, with radiotherapy) can reduce the number of patients who need to undergo surgery. Neo-adjuvant radiotherapy can also reduce the complexity of surgery where this is eventually required.101346
How can I estimate prognosis?
Prognosis is highly variable and any attempt at estimating survival in MBD should be with input from oncology.11 Patients with solitary metastases from renal and breast primaries have a median survival of 5-7 years.143854 Patients with a poorer prognosis may still benefit from orthopaedic input to relieve pain and maximise mobility.
Factors favouring survival include low volume oligometastatic disease, certain types of primary cancer (eg, breast, renal, thyroid, myeloma, or lymphoma),55 patient fitness,56 and a long disease-free interval between primary and recurrence.38 Factors indicating a shorter prognosis (ie, less than six months) include high volume “polymetastatic” disease, multiple “organs” involved, pathological fracture, and significant biochemical abnormalities (eg, low albumin or high calcium).4144955 The Ratasvuori score (table 2) can help to estimate prognosis.56 It is a simple score based on primary type, presence of bone/organ metastases, and functional status.57
Considerations for shared decision making
When breaking the news of cancer recurrence or spread, considering how to communicate information can help avoid causing further distress to patients.58 Several methods are available for structuring this discussion, such as the SPIKES method commonly used in primary care.5960 Take care to set up the interview in a supportive environment with no interruptions.59 Give patients the opportunity to indicate how much information they are comfortable with initially, with an option to continue the conversation at a later date. Information should be shared in small chunks at a suitable pace.61 Patients appreciate a gradual build-up of information with suitable “warning shots.”61 It helps to finish the interview by agreeing a clear plan for what happens next. Discuss any practical issues such as transport, immediate emotional support, or help in relaying news to key family members.
Interim pain management methods include restricted weightbearing with a stick or crutches.1417 Pain relief should follow the World Health Organization pain ladder, with use of anti-inflammatories where tolerated and fast acting opiates for pain exacerbations.14286263 When treating cancer induced bone pain, refer to the 2015 BMJ clinical review,28 NICE cancer pain management scenarios,64 and the Cancer Pain Management leaflet from the British Pain Society.65
The prognosis for many patients with bone metastases is no longer poor.143855 Early referral for specialist management can lead to better survival, reduced need for surgery,3846 and better outcomes for those who do need surgery.4050
How patients were involved in the creation of this article
This article has been reviewed by a lay member of a regional ethics committee with extensive experience in reviewing medical research applications for readability, language, and ethical treatment of NHS patients. This enhanced the readability of the article by amending some technical terminology and improving clarity of the figures for use by primary care physicians.
How this article was created
This article was based on guidance published in 2015 by the British Orthopaedic Oncology Society on Good Practice in Metastatic Bone Disease,12 which updated previous guidance from the British Association of Surgical Oncology.11
Recommendations have been supplemented by international guidelines from Japan and Europe,414 and a thorough literature review including the Cochrane, Medline, and Web of Science databases and a citation search for both published national guidelines. Search terms used included “bone metas*”,“bone cancer”,“secondary bone cancer”, and “pathological fracture”. The guidance provided in this article has been reviewed and approved by specialists in orthopaedics, oncology, radiology, and primary care.
Education into practice
How do you follow up patients with a history of cancer who present with musculoskeletal pain?
How often do patients in your care/practice with new bony metastases undergo urgent radiographic imaging within 10 days of presentation?
Think about the last time you spoke to a patient about a new diagnosis of metastatic bone disease. How confident were you about what to tell them? How might you change this conversation the next time?
Acknowledgments: The authors would like to acknowledge the contribution of Matthew Moran, consultant orthopaedic oncology surgeon, Alison Stillie, consultant clinical oncologist, and Robert Ashford, president of the British Orthopaedic Oncology Society for their significant input into the content and accuracy of this article. The authors also gratefully acknowledge the input of Lorna McLeish, lay member of the east of Scotland research ethics service, for her input regarding content, readability, and ethical considerations arising from the recommendations put forth in this article.
Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none.
The BMJ policy on financial interests is here: https://www.bmj.com/sites/default/files/attachments/resources/2016/03/16-current-bmj-education-coi-form.pdf.
Provenance and peer review: commissioned; externally peer reviewed.