This feature has been funded by Janssen UK as part of the Make Blood Cancer Visible campaign and written on the company’s behalf by M&F Health, based on an interview with Dr Pawan Randev. The views expressed in this feature are his own and do not represent any other entity.
Why is recognising blood cancer so challenging?
Diagnosing blood cancers is often difficult in primary care – partly because the individual conditions are relatively rare. “Depending on local demographics, a GP may see a case of childhood leukaemia once every three to five years. They may see a myeloma once every three years,” says Dr Randev. “It’s difficult to gain experience with that caseload.”
To complicate matters further, blood cancers have, Dr Randev notes, “very diverse presentations”. For example, acute leukaemia often has a dramatic onset: 65% of acute lymphoblastic leukaemia cases present as emergencies.9 Moreover, 37% of UK myeloma patients are diagnosed following an emergency presentation, which is associated with a poor prognosis.10 Only 51% of those diagnosed with myeloma following an emergency presentation survive for a year compared with 81% of those who were not.10
On the other hand, chronic leukaemia is often indolent.3 For example, early or intermediate chronic lymphocytic leukaemia tends to be diagnosed as an incidental finding.11 Twenty per cent of patients with chronic myeloid leukaemia are diagnosed incidentally.12
“The lack of distinctive symptoms is the main issue facing GPs trying to detect blood cancers. Most symptoms of blood cancers are vague.”13 Dr Randev says. “Lymph node pain after drinking alcohol is, for example, a classic symptom of Hodgkin's lymphoma.14 But this symptom is quite rare. There are often no red flag symptoms until the later stages of blood cancers. Nevertheless, several clinical indicators may suggest that prompt referral is needed.”
Why is there a delay in recognising blood cancer?
A growing number of studies suggest that, if the primary care team had a higher index of suspicion, blood cancers might be diagnosed more rapidly.5, 6, 7, 8 Given the rarity of some blood cancers and the fact that the constitutional symptoms could arise from many different causes, it’s not surprising that GPs may misattribute symptoms to more common ailments, especially as many patients have significant co-morbidities and require polypharmacy. So, fatigue could be a symptom of a blood cancer,13 “but it may also arise from heart failure, chronic obstructive pulmonary disease, osteoarthritis or as a medication side effect.” Dr Randev says.
For instance, several GPs regarded back pain – which, with the benefit of hindsight, was due to myeloma – as mechanical, and prescribed analgesics, anti-inflammatories, and recommended consulting a physiotherapist or osteopath.5
Other studies confirm the delay in diagnosis. An analysis of 17,042 patients with a new cancer diagnosis during 2014 from 439 GP practices in England reported a median diagnostic interval of 40 days.7 Blood cancers were broadly in line with the overall results.6 GPs, however, felt that avoidable delays occurred in 14.7% of leukaemia cases, 26.3% of lymphomas and 27.3% of multiple myelomas.6 Furthermore, the 2017 National Cancer Patient Experience Survey in England found that 28% of patients with blood cancers needed at least three GP consultations before referral.7
How can a diagnosis be confirmed?
The vague, ambiguous signs and symptoms mean that the diagnosis of blood cancers depends on laboratory findings. Hypercalcaemia and leucopaenia with raised ESR and normochromic anemia, for example, are particularly important and coupled with symptoms, “strongly suggest myeloma”.10 If ordering blood chemistry, it’s important to specify calcium levels. Hypercalcaemia can be a sign of blood cancer.”15 agrees Dr Randev.
“Protein electrophoresis and other immunohistochemistry tests can confirm or exclude the diagnosis of some blood cancers.16 Hodgkin's lymphoma in the chest can cause symptoms such as cough, shortness of breath or pain14 and a chest x-ray may reveal enlarged lymph nodes.17 It’s important to request radiography when someone presents with symptoms such as back or bone pain or an enlarged lymph node.”
A low threshold for ordering blood and other tests is important to improve early diagnosis. Even blood tests aren’t always definitive. “Full blood counts can be normal in some blood cancers such as lymphoma. A person with blood cancer fatigue may not show changes on the initial blood count,” says Dr Randev.
“Patients and GPs are, naturally concerned about cancer. So, performing the tests can offer reassurance to patients and the doctor. In many cases, however, GPs will need to deal with considerable uncertainty, which can be stressful. But a detailed examination and safety netting of symptoms allows you to develop a management plan, whether or not the symptoms arise from a blood cancer,” Dr Randev says.
Yet GPs should not rely on laboratory tests alone: they also need their clinical acumen. “The art of medicine is knowing when something doesn’t seem right for that patient, based on the GP’s knowledge of the person and their family. Lymph nodes can enlarge during acute infections.”18 Dr Randev says. “However if the nodes remain enlarged, then GPs should step back and reassess the diagnosis.”
What are the recommendations around blood cancer referrals?
Early diagnosis and rapid referral are the foundation of management for blood cancers. NICE’s suspected cancer, recognition and referral pathway (NG12) for leukaemia, myeloma and NHL and Hodgkin's lymphoma includes recommendations on the symptoms and signs that warrant investigation and referral for suspected cancer.19
“NG12 includes a list of symptoms which can be difficult to use in everyday clinical practice. The award winning GatewayC Cancer Maps, developed by Ben Noble can be easier to use during a busy consultation,” Dr Randev says.
GatewayC Cancer Maps, which is approved by NICE and the Royal College of General Practitioners (RCGP), is an interactive online tool to help clinicians assess possible cancer symptoms during consultations. “Using Cancer Maps, you input the symptoms, age and sex,” Dr Randev explains. “The program highlights on the most likely differential diagnoses and the suggested actions. GatewayC also includes educational modules covering myeloma, chronic leukaemia and lymphoma diagnosis, which can contribute to continuing professional development.”
How can diagnosis be improved?
Despite these innovations, delays in diagnosis will, inevitably occur. The RCGP Early Diagnosis of Cancer Significant Event Analysis Toolkit allows primary care practices to determine if there was an avoidable delay in patients who do not meet target referral times.20 “We now use the term Learning Event. These have long been part of GP appraisal, but Learning Events are an excellent tool to spread information in a structured way through Primary Care Networks especially for less common conditions.” says Dr Randev, who was involved in the toolkit’s development. “Traditionally, we don’t share these across practices. However, this is a missed opportunity.”
Dr Randev suggests consolidating Learning Events from rare conditions collected by several practices. “When you reach 100-200 cases, the data is a powerful means to identify issues, drive improvements and address common features between practices, such as poor patient health literacy.” Dr Randev comments. “The learning events can be shared with colleagues, such as Physician Associates, Nurse Practitioners, Clinical Pharmacists and other front-line staff. The entire team and network can benefit.”
“The increasing primary care workload makes finding the time to make a considered diagnosis of blood cancers difficult. Many GPs also worry about the medicolegal implications of missing a case of cancer.” Dr Randev concludes. “Handling uncertainty can be difficult, especially for less experienced GPs. We should encourage safety-netting for patients where there is uncertainty, reviewing at appropriate intervals and documenting that this has been done.21 Fortunately, a growing range of resources help GPs diagnose blood cancers rapidly and refer patients quickly, which should help improve outcomes. However, the primary care team needs to maintain a high level of awareness for blood cancers.”
To find a summary of the educational materials and referral tools available to help support primary care professionals in the recognition of blood cancers, please visit http://www.makebloodcancervisible.co.uk/healthcare-professionals.
Date of preparation: November 2019
Job code: CP-104849
- APPG on Blood Cancer. The Hidden Cancer. Available at: https://bloodwise.org.uk/sites/default/files/documents/appg_report_on_blood_cancer.pdf. Last accessed November 2019.
- Shafique S and Tehsin S Computer-aided diagnosis of acute lymphoblastic leukaemia Computational and Mathematical Methods in Medicine 2018;2018:6125289-6125289.
- Storck K, Brandstetter M, Keller U et al Clinical presentation and characteristics of lymphoma in the head and neck region Head & Face Medicine 2019;15:1.
- Howell DA, Hart RI, Smith AG et al Myeloma: Patient accounts of their pathways to diagnosis PLOS One 2018;13:e0194788.
- Howell DA, Hart RI, Smith AG et al Disease-related factors affecting timely lymphoma diagnosis: A qualitative study exploring patient experiences British Journal of General Practice 2019;69:e134-e145.
- Swann R, McPhail S, Witt J et al Diagnosing cancer in primary care: Results from the National Cancer Diagnosis Audit British Journal of General Practice 2018;68:e63-e72.
- National Cancer Patient Experience Survey. Available at www.ncpes.co.uk/reports/2017-reports/national-reports-2/3580-cpes-2017-national-results/file. Last accessed November 2019.
- WHO. Guide to Cancer Early Diagnosis. 2017. Available at: https://apps.who.int/iris/bitstream/handle/10665/254500/9789241511940-eng.pdf;jsessionid=92D5E3975A6D81453C89A215FF325D02?sequence=1. Last accessed November 2019.
- Leukaemia Care Can you spot leukaemia? Available at https://www.leukaemiacare.org.uk/support-and-information/for-healthcare-professionals/gp-learning/ Last accessed November 2019.
- Shephard EA, Neal RD, Rose P et al Quantifying the risk of multiple myeloma from symptoms reported in primary care patients: A large case–control study using electronic records British Journal of General Practice 2015;65:e106-e113.
- Zent CS and Kay NE Management of patients with chronic lymphocytic leukemia with a high risk of adverse outcome: The Mayo Clinic approach Leukemia & Lymphoma 2011;52:1425-1434.
- Davis AS, Viera AJ, and Mead MD Leukemia: An overview for primary care American Family Physician 2014;89:731-8Last accessed November 2019.
- Bloodwise. Blood Cancer Symptoms. Available at: https://bloodwise.org.uk/info-support/blood-cancer/symptoms. Last accessed November 2019.
- Cancer Research UK. Hodgkin Lymphoma. Symptoms. Available at: https://www.cancerresearchuk.org/about-cancer/hodgkin-lymphoma/symptoms. Last accessed November 2019.
- Cancer Research UK. Coping with cancer. High calcium in people with cancer. Available at: https://www.cancerresearchuk.org/about-cancer/coping/physically/blood-calcium/high-calcium-people-cancer. Last accessed November 2019.
- University of Rochester Medical Center. Protein Electrophoresis (Blood). Available at: https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=protein_electrophoresis_serum. Last accessed November 2019.
- Cancer Research UK. Hodgkin Lymphoma. Chest x-rays. Available at: https://www.cancerresearchuk.org/about-cancer/hodgkin-lymphoma/getting-diagnosed/tests-stage/chest-x-ray. Last accessed November 2019.
- NHS. Swollen glands. Available at: https://www.nhs.uk/conditions/swollen-glands/. Last accessed November 2019.
- NICE Suspected cancer: recognition and referral. Available at www.nice.org.uk/guidance/ng12. Last accessed November 2019.
- RCGP. Early Diagnosis of Cancer Significant Event Analysis Toolkit. Available at: https://www.rcgp.org.uk/clinical-and-research/resources/toolkits/early-diagnosis-of-cancer-significant-event-analysis-toolkit.aspx. Last accessed November 2019.
- Nicholson D et al. The BMJ. Can safety-netting improve cancer detection in patients with vague symptoms? 2016;355:i5515. Published 09 November 2016.