Oncologic emergencies

• Oncologic emergencies are life-threatening complications of cancer or its treatment. This page covers five: tumour lysis syndrome, superior vena cava syndrome, metastatic spinal cord compression, hypercalcaemia of malignancy, and neutropenic fever.
• Each is a medical emergency. Start treatment before the diagnosis is final, because delay causes kidney failure, paralysis, arrhythmia or septic shock.
• The first steps are nearly always the same: secure the airway, give oxygen, obtain intravenous access, send blood and start targeted therapy (fluids, dexamethasone, antibiotics or bronchodilator-style supportive care) as the clinical picture dictates.
• The cause is usually the tumour itself, not infection. Treat the tumour where possible, but first protect the patient from the cascade the tumour has triggered.
• Prognosis is usually good if the emergency is caught early; the danger lies in not recognising it.

By the end of this page you should be able to:

1. Recognise each of the five emergencies from the presenting history and examination.
2. Explain the pathophysiology that links the tumour to the clinical picture.
3. State the first-line investigations and the numbers that define the condition.
4. Outline the first 24 hours of management, with doses and monitoring.
5. Know which complications change the plan, and what to do when resources are limited.
6. Counsel a patient or relative about urgency and what treatment aims to achieve.

Oncologic emergencies are conditions in which a cancer, or its treatment, threatens life within hours to days. They do not all announce themselves loudly: a patient on chemotherapy may simply develop a fever, and a patient with back pain may be heading for paraplegia. The common thread is that the tumour has created a physiological crisis faster than the body can compensate.

This page treats five emergencies together because they share a way of thinking. In each, an underlying malignancy produces a biochemical or mechanical problem (urate crystals, a blocked vein, a compressed cord, excess calcium, a collapsed neutrophil count); the emergency is the downstream failure (renal failure, cerebral oedema, neuronal death, arrhythmia, sepsis). Good care means reversing the downstream problem while the oncologists deal with the upstream tumour.

Each section below gives definition, mechanism, how it presents, what to check and what to do. The final sections give red flags, pregnancy and age-specific cautions, low-resource notes, key points, and a check-yourself.

Tumour lysis syndrome (TLS) is the metabolic wreckage that follows rapid death of a large mass of cancer cells. Their contents flood the bloodstream faster than the kidneys and other organs can clear them.

TLS occurs most often in rapidly growing, high-burden haematological cancers such as Burkitt lymphoma, acute lymphoblastic leukaemia and diffuse large B-cell lymphoma, and increasingly after targeted or immune therapies in solid tumours. Spontaneous TLS, before any treatment, is well described, particularly in children and in bulky disease. Risk rises with dehydration, pre-existing kidney disease, high lactate dehydrogenase (LDH), bulky or metastatic disease, and leucocytosis.

When cancer cells break up, they release potassium, phosphate and nucleic acids. Nucleic acids are metabolised to uric acid. The kidneys face four problems at once:

1. Potassium rises and can cause cardiac arrhythmia.
2. Uric acid precipitates in renal tubules, obstructing flow.
3. Phosphate binds calcium, producing hypocalcaemia and calcium-phosphate crystals that also obstruct tubules.
4. The combined crystal and urate burden causes acute kidney injury, which then traps the other metabolites in the blood.

This is why early fluids are not optional: they keep urine flowing and dilute the crystals.

Diagnosis needs two or more of the following laboratory criteria, measured when treatment begins (pre-treatment values may be lower), together with the timing rules in the original paper: an elevated uric acid, potassium or phosphate, or a low calcium, or a 25% rise or fall compared with baseline. In adults the thresholds are: uric acid 476 micromol/L or higher, potassium 6 mmol/L or higher, phosphate 1.45 mmol/L or higher (2.1 mmol/L or higher in children), and calcium 1.75 mmol/L or lower. Clinical TLS is laboratory TLS plus one of acute kidney injury, cardiac arrhythmia, seizure or sudden death.^[4]

A practical point for the bedside: a rising creatinine with a new hyperkalaemia in a patient with high-grade lymphoma in the first few days after chemotherapy is TLS until proven otherwise.

Prevention is easier than rescue. For patients at intermediate or high risk, start hydration before chemotherapy and continue through the period of risk, use a urate-lowering drug, and monitor electrolytes closely.^[4]

• Hydration. Aim for generous oral or intravenous fluids so that urine output is maintained; match the volume to the patient's volume status and heart function, and monitor for fluid overload.
• Urate lowering. Allopurinol (typically 300 mg daily for 5 days) is suitable for low- to intermediate-risk patients. Rasburicase, a recombinant urate oxidase, is preferred for high-risk patients and for established TLS.^[4]
• Monitoring. Check urea, creatinine, potassium, phosphate, calcium and urate frequently during the at-risk period, as often as every few hours in high-risk patients.
• Bicarbonate. Routine urine alkalinisation is no longer recommended; it promotes calcium-phosphate precipitation. Reserve any bicarbonate use for a defined indication.

Once TLS is established, management is four-track: fluids, correction of potassium, urate lowering, and management of calcium-phosphate.

1. Fluids. Isotonic saline intravenously, with the aim of a high urine output, unless the patient is fluid-overloaded or oliguric. Insert a urinary catheter only if there is urinary retention or the patient cannot pass urine; many patients need one simply to measure output.
2. Potassium. Stop all potassium intake. Give calcium gluconate to stabilise the myocardium if the ECG shows hyperkalaemia. Use insulin with glucose, or salbutamol, to shift potassium intracellularly. Dialysis is indicated for refractory hyperkalaemia.
3. Urate. Rasburicase is preferred because it acts within hours (median time to uric acid control about 4 hours) rather than days (about 27 hours for allopurinol).^[4] Dosing in current practice ranges from 0.15 to 0.20 mg per kilogram daily, capped at 6 mg; a single dose of 0.2 mg/kg is effective in roughly 98% of patients, with no serious adverse events in a large real-world cohort.^[4] Rasburicase is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficiency because of methaemoglobinaemia and haemolysis; screen patients at risk, especially those of African, Asian, Middle-Eastern or Mediterranean origin. Allopurinol (300 mg daily) remains an alternative when rasburicase is unavailable or contraindicated.
4. Calcium and phosphate. Do not treat asymptomatic hypocalcaemia; calcium is given only for neuromuscular or cardiac symptoms, because giving calcium when phosphate is high precipitates calcium-phosphate. Use phosphate binders and restrict phosphate intake. Avoid routine bicarbonate.
5. Dialysis. Indicated for refractory hyperkalaemia, anuria, volume overload, severe or symptomatic hypocalcaemia, or rapidly rising creatinine. Continuous renal replacement therapy is often used in the intensive care unit.

• Up to one-third of patients with TLS need dialysis, and around 15% of cases are fatal.^[4]
• Rasburicase normalises uric acid in about 97 to 98% of patients within 24 hours of a first dose.^[4]
• Allopurinol for 5 days controlled uric acid in 66% of hyperuricaemic patients versus 87% for rasburicase in a randomised comparison.^[4]
• Elderly patients and those with cardiac disease tolerate large fluid volumes poorly; watch for pulmonary oedema.

Superior vena cava syndrome (SVCS) is the set of signs and symptoms produced when the superior vena cava, the large vein returning blood from the head, neck and upper limbs to the heart, is compressed or thrombosed. It is itself a clinical diagnosis; the underlying cause is what matters. ^[6]

Malignant disease is still the leading cause, in roughly 90% of cases. The commonest culprits are lung cancer (especially small cell and squamous non-small cell cancer), lymphoma, germ-cell tumours and thymoma, with metastases to the mediastinum the next most common. Benign causes (central venous catheters, pacemaker leads, benign tumours) are a growing minority. The syndrome develops when the normal collateral venous drainage through the azygos system cannot keep up with the obstruction. ^[6]

Presentation ranges from mild to life-threatening, and the speed of onset matters as much as the degree. Acute obstruction produces facial and arm swelling, dilated neck and chest wall veins, dyspnoea, cough, dysphagia, hoarseness and headache, and can progress to cerebral or laryngeal oedema with altered consciousness and stridor. Chronic obstruction allows collaterals to develop, so symptoms are milder: upper limb heaviness, swelling and skin discoloration.

A commonly used clinical grading system, proposed by Yu and colleagues, has six grades:^[6]

Grades 4 and 5 are true emergencies and need airway protection and urgent decompression.

Contrast-enhanced CT of the chest is the preferred test (sensitivity 96%, specificity 92%) and shows the level and cause of the obstruction, the collaterals, and the tumour.^[6] Duplex ultrasound can show acute thrombosis of neck and arm veins but is less useful for the deeper obstruction. MRI has a role but is affected by mediastinal movement and pacemaker leads.

The principle is to treat the symptom emergency first and the tumour second. Treatment choice depends on the cause, the severity, and how ill the patient is.

• Symptomatic measures. Elevate the head, give oxygen, give diuretic and corticosteroid where there is laryngeal or cerebral oedema. These are temporising.
• Stent. Endovascular stenting gives the fastest relief, with technical success near 99% and clinical success near 93% in one meta-analysis; up to 97 to 99% of patients report rapid symptom relief.^[6] It is used for severe or life-threatening obstruction, for obstruction not sensitive to chemotherapy or radiotherapy, or as a bridge when treatment will be slow. Life-threatening thrombosis may need thrombolysis before stenting.
• Radiotherapy. Often the usual treatment for radiosensitive or slowly growing tumours (lymphoma, small-cell lung cancer, metastases) in patients who are not immediately threatened. Relief typically takes days to weeks, so it is not the answer for grade 4 disease.
• Chemotherapy. First-line for chemotherapy-sensitive tumours, especially small-cell lung cancer and germ-cell tumours, sometimes given with radiotherapy.
• Anticoagulation. Used when thrombosis is part of the picture and after stenting, although no regimen has shown better stent patency than another.^[6]
• Defining the tumour. Tissue diagnosis (bronchoscopy, biopsy, node sampling) should be obtained whenever it can be done safely, because the treatment follows the histology. Stenting first and biopsying second is a reasonable sequence when the patient is unstable.

In practice, the fastest reliable relief is a stent; where stents are not available, radiotherapy is the usual option, and grade 4 disease may need intensive care support.

Metastatic spinal cord compression (MSCC) is compression of the spinal cord or cauda equina by a tumour or by bone collapsing after tumour infiltration. It is one of the few oncological emergencies in which the outcome is permanent if the diagnosis is late: the level of neurological function at presentation is the strongest predictor of what function the patient keeps.

Any cancer can do it, most often breast, lung and prostate cancer, and myeloma. Compression usually arises from vertebral body collapse or from tumour extending into the epidural space. Look for a past or current cancer and new back pain.

The classic history builds in stages: back pain first, then radicular pain, then sensory change, then weakness, then bladder or bowel disturbance. New back pain in a cancer patient is MSCC until proven otherwise; most patients have had pain for days or weeks. Ask about walking, passing urine and opening the bowels.

Urgent MRI of the whole spine is the investigation of choice, to be done as soon as possible and always within 24 hours when MSCC is suspected.^[5]

CT is used only if MRI is contraindicated. Plain X-ray should not be relied on to diagnose or exclude the condition.^[5]

Speed matters. Neurological function at presentation predicts long-term function, so treat on suspicion.

1. Immobilise. Start immobilisation at once if there are neurological symptoms or signs suggesting spinal instability, and consider it for everyone with moderate to severe pain on movement. Nurse supine (flat or partially elevated) and seek specialist imaging advice early.^[5]
2. Dexamethasone. For patients with neurological symptoms or signs of MSCC, give 16 mg of oral dexamethasone (or an equivalent parenteral dose) as soon as possible. After the first dose, give 16 mg daily for patients awaiting surgery or radiotherapy. Reduce gradually after surgery or at the start of radiotherapy until stopped.^[5] If dexamethasone is given before imaging and MSCC is then excluded, stop it.^[5]
3. Imaging. Whole-spine MRI as above; overnight MRI only where urgent diagnosis is needed so that treatment can start immediately.^[5]
4. Radiotherapy. For patients not suitable for spinal surgery, give urgent radiotherapy (as soon as possible and within 24 hours) unless they have had complete paraplegia or tetraplegia for 2 weeks or more with well-controlled pain, or an overall poor prognosis. The standard dose is 8 Gy as a single fraction unless the patient is at high risk of radiation side-effects, in which case multiple fractions are considered.^[5]
5. Surgery. Used for mechanical instability, progressive neurological deficit, recurrence at a previously irradiated level, unknown primary, radioresistant tumour, or bony compression with cord compromise. The decision sits with the spinal surgery and oncology teams.
6. Supportive care. Analgesia promptly; proton pump inhibitor protection and glucose monitoring for anyone on dexamethasone; rehabilitation planning from the start.^[5]

About 8 Gy single fraction is also the standard for painful spinal metastases without cord compression.^[5]

Hypercalcaemia of malignancy (HCM) is a common metabolic complication of advanced cancer, with a prevalence of 2 to 30% depending on cancer type and stage. It most often accompanies breast cancer, lung cancer, renal cancer and myeloma. It is usually driven by parathyroid hormone-related protein (PTHrP, about 80% of cases) or by osteolytic bone metastases (about 20%); calcitriol-mediated hypercalcaemia, usually from lymphoma, is a less common cause. ^[1]

By corrected serum calcium: mild under 3.0 mmol/L, moderate 3.0 to 3.5 mmol/L, severe over 3.5 mmol/L.^[1] Mild disease causes fatigue, constipation and cognitive slowing. Severe or rapidly rising calcium produces nephrogenic diabetes insipidus, dehydration and renal failure, and can precipitate arrhythmia.

Whatever the driver, the common pathway is increased osteoclastic bone resorption. PTHrP mimics parathyroid hormone and drives calcium out of bone and renal calcium retention. In bone metastases, local cytokines activate osteoclasts. In calcitriol-mediated disease, intestine and bone absorb more calcium. Treatment therefore aims first to dilute and excrete calcium, then to shut down osteoclast activity, while treating the cancer.

Check corrected (or ionised) calcium, phosphate, urea, creatinine, magnesium, albumin, and (if the type is unclear) PTH and PTHrP. Watch the ECG; hypercalcaemia shortens the QT interval. Review medications and hydration.

The algorithm differs by severity and by mechanism.

Every patient: fluids first. Isotonic intravenous saline (0.9%) to correct volume depletion is first-line. Rates of 200 to 500 mL per hour may be needed, with monitoring for volume overload. Loop diuretics are not routinely recommended, but may be considered in patients at risk of volume overload, such as cardiac or renal impairment.^[1]

Urgent relief in severe disease. In severe hypercalcaemia, add salmon calcitonin (4 to 8 units per kilogram subcutaneously, three or four times daily for 2 to 3 days), because it acts within hours while the antiresorptive takes effect. Calcitonin causes tachyphylaxis after 2 to 3 days, so it is a bridge.^[1]

Antiresorptive treatment (the definitive step). The Endocrine Society guideline suggests using denosumab in preference to intravenous bisphosphonates as first-line pharmacological treatment.^[1] At the bedside the picture is more complicated, because denosumab is licensed for bisphosphonate-refractory HCM but not as first-line by the FDA, and it is not licensed for HCM in the UK or European Union. Many services therefore still use zoledronic acid first. Both are acceptable options; say so, and note that guidelines differ.

• Zoledronic acid: 4 mg intravenously over 15 to 30 minutes; can be repeated after 7 days and then every 3 to 4 weeks. Use 3 mg over 30 minutes if creatinine clearance is 30 to 60 mL per minute, and avoid if creatinine clearance is under 30 mL per minute.^[1]
• Pamidronate: 90 mg intravenously over 2 hours (60 mg over 4 hours if creatinine clearance is 30 to 60 mL per minute; contraindicated under 30).^[1]
• Denosumab: 120 mg subcutaneously, repeated after 1, 2 and 4 weeks, then monthly. Can be used in renal impairment; hypocalcaemia is more common.^[1]

Special mechanisms.

• Calcitriol-mediated hypercalcaemia (usually lymphoma): first-line treatment is high-dose glucocorticoids: hydrocortisone 200 to 400 mg per day for 3 to 5 days, or prednisolone 60 mg per day for 10 days; add an antiresorptive if calcium is still poorly controlled.^[1]
• Parathyroid carcinoma: cinacalcet 30 mg twice daily initially, titrated up to 90 mg four times daily, plus antiresorptives as needed.^[1]

Good-practice points. Review dental health before giving an antiresorptive; check renal function before IV bisphosphonates; replace magnesium and phosphate; check and replace vitamin D; arrange oncology review for cancer treatment, which is the real fix. Bisphosphonates and high-dose steroids together raise the small risk of osteonecrosis of the jaw and atypical fracture.

Neutropenic fever (often called neutropenic sepsis) is a temperature of 38 °C or higher, or other signs consistent with clinically significant sepsis, in a patient whose neutrophil count is 0.5 × 10^9 per litre or lower during anticancer treatment.^[2] It is the emergency you will see most often. It is common in patients on chemotherapy, and a minority of those affected develop life-threatening complications; risk stratification separates them.

Significant neutropenia means a neutrophil count of 0.5 × 10^9 per litre or lower. The period of highest risk is the nadir, after the neutrophil count falls during cytotoxic chemotherapy. Delays in antibiotics, not the neutropenia itself, are what kill patients.

The Multinational Association for Supportive Care in Cancer (MASCC) risk index is the most widely validated triage tool. It combines seven clinical variables. A score of 21 or higher identifies low-risk patients, with a positive predictive value of 91% for not developing serious complications.^[3] Those patients may be managed in an outpatient or ambulatory setting; those with a score under 21 are high-risk and need standard inpatient neutropenic sepsis management.^[3]

The important caveat is that the MASCC score is not validated in patients treated with combined chemotherapy and immune checkpoint inhibitors, so apply clinical judgement there.

There is no time to wait.

1. Treat as an emergency. Start empiric antibiotics immediately, and blood cultures should be taken first if they can be obtained without delay, including an additional peripheral culture if the patient has a central venous access device.^[2]
2. Initial assessment. History and examination; full blood count, urea, creatinine, electrolytes, liver function, albumin, C-reactive protein, lactate and blood cultures. Do not do a chest X-ray unless clinically indicated.^[2]
3. First-line antibiotic. Beta-lactam monotherapy with piperacillin with tazobactam is the recommended initial empiric intravenous therapy unless there are patient-specific or local microbiological contraindications.^[2] Other guideline-acceptable monotherapies in different regions include ceftazidime or meropenem, but your local guideline and microbiology profile should decide. Do not add an aminoglycoside routinely.^[2]
4. Do not give empiric glycopeptides for suspected neutropenic sepsis in patients with a central venous access device unless there is a specific microbiological indication, and do not remove the line as part of initial management.^[2]
5. Supportive care. Fluids, oxygen, antipyretics, analgesia, nutritional support, and daily reassessment of risk with a validated score.^[2][3]
6. Duration. Continue empiric antibiotics in patients with unresponsive fever unless an alternative cause of fever is likely. Withdraw empiric antibiotic therapy once the sepsis has responded, irrespective of the neutrophil count.^[2] Do not switch initial antibiotics for unresponsive fever unless the patient deteriorates or there is a microbiological reason.^[2] Transfer from intravenous to oral therapy is possible after 48 hours once risk is reassessed as low.^[2]
7. Prophylaxis. In adults with expected significant neutropenia from chemotherapy (acute leukaemias, stem-cell transplant or solid tumours) prophylactic fluoroquinolone (ciprofloxacin in the UK) is offered during the expected neutropenic period only; it is not routine G-CSF unless G-CSF is part of the regimen or needed to maintain dose intensity.^[2]

Chemotherapy-immune-checkpoint-inhibitor combinations are now standard for several cancers. In that setting:

• Suspect ICI-mediated neutropenia if the timing is unexpected, or if grade 3/4 neutropenia persists 10 days after administration. Incidence is under 1%, with a median onset of 3 cycles, often severe.^{[3] [6]}
• Initial treatment of suspected ICI-mediated neutropenia is high-dose steroids (for example 1 mg per kilogram oral prednisolone) plus short-acting granulocyte colony-stimulating factor (G-CSF). Escalate to IV immunoglobulin or cyclosporine if first-line treatment fails, guided by bone marrow findings.^[3]
• Do not give high-dose steroids empirically for febrile neutropenia with grade 3 or higher diarrhoea or transaminitis when a septic picture or chemotherapy toxicity is more likely, unless strongly suspected ICI toxicity persists after treating the sepsis.^[3]
• If adrenal insufficiency from ICI is possible and the patient has been given steroids as anti-emetic prophylaxis, it is hard to diagnose biochemically in the acute septic episode.^[3]

For confirmed low-risk neutropenic fever (MASCC 21 or higher), ambulatory or outpatient antibiotic therapy with a broad-spectrum oral agent, clear safety-netting and review within 72 hours can be safe and cost-effective, provided the patient has support at home and lives within reach of hospital.^[3]

• Fever 38 °C or higher during chemotherapy with a low or unknown neutrophil count: treat as an emergency.
• A cancer patient with new back pain, paraesthesia, leg weakness or sphincter disturbance: MSCC until proven otherwise.
• Facial or arm swelling with dyspnoea or altered consciousness: SVCS, possibly life-threatening.
• Confusion or excessive thirst with a high corrected calcium.
• A rising creatinine and potassium after starting treatment for Burkitt lymphoma or leukaemia.
• Dehydration, oliguria, or new arrhythmia in a patient with TLS risk factors.

• Children. Tumour lysis is commoner and more severe after induction for acute lymphoblastic leukaemia and Burkitt lymphoma. G6PD deficiency, and the need for different rasburicase dosing, matter more. Growth factor prophylaxis and antibiotic prophylaxis follow paediatric protocols.
• Pregnancy. Chemotherapy and radiotherapy decisions, and dexamethasone use, must be made with obstetric and oncology teams. Febrile neutropenia is treated with the same urgency and similar antibiotics, checking teratogenicity.
• Older adults. Tolerate fluids less well (heart failure, renal impairment), so watch for pulmonary oedema. Drug toxicity and delirium complicate assessment.
• Immunocompromised patients (HIV, transplant, corticosteroid use) can become septic with low-grade or absent fever; do not be reassured by a normal temperature.

• Neutropenic fever. Time to antibiotics matters more than which antibiotic. Blood cultures, a thermometer and a first dose of a broad-spectrum beta-lactam are achievable in most settings. If piperacillin-tazobactam is unavailable, use ceftazidime or meropenem according to local guidance. MASCC-based outpatient pathways are harder to run without transport and reliable follow-up; admit if in doubt.
• Tumour lysis. Fluids, allopurinol and careful electrolyte monitoring will save many patients. Rasburicase may be unavailable or unaffordable; allopurinol is the fallback. Dialysis is often not available; transfer early if creatinine or potassium is rising.
• Spinal cord compression. MRI may not exist; recognise the clinical syndrome, immobilise and start dexamethasone while arranging transfer for imaging or radiotherapy. A fractionated course of radiotherapy may be the only neurosurgical resource available.
• SVCS. Recognise severe (grade 4) disease by altered consciousness, stridor, hypotension and renal impairment. Stents may not be available; radiotherapy or chemotherapy are the usual options, with diuretics, steroids and oxygen as temporising measures.
• Hypercalcaemia. Saline, calcitonin and loop diuretics used with care are widely available. Zoledronic acid and denosumab depend on supply; zoledronic acid is cheap in many settings, denosumab may not be.

In every case, the tumour has produced a faster problem than the tumour itself. The immediate job is to buy time for oncology to take over: dilute, oxygenate, support, decompress, and do not be too proud to start treatment before the scan report arrives.