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Cancer of unknown primary

Essential points for quick revision.

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Escalate

Treat spinal cord compression, airway or superior vena cava obstruction, bowel obstruction, severe bleeding, sepsis, pathological fracture, symptomatic brain metastasis and severe hypercalcaemia immediately. The absence of a known primary must not delay physiological rescue, corticosteroid or radiotherapy discussion where indicated, or urgent surgical and acute-oncology involvement.

Synopsis

Recognise metastatic malignancy without an identified origin, stabilise urgent complications, perform a focused high-yield diagnostic work-up, and avoid burdensome testing that cannot change treatment or goals.

  • Malignancy of undefined primary describes metastatic cancer before a full initial assessment; confirmed cancer of unknown primary remains after appropriate investigation fails to identify origin.
  • First confirm malignancy and lineage with adequate tissue; poorly planned broad imaging or tumour markers cannot substitute for pathology.
  • History, full examination, basic blood tests and contrast CT chest, abdomen and pelvis form the initial diagnostic core under NICE guidance.

Key red flags

Acute metastatic complication

Neurological deficit, obstruction, severe pain, pathological fracture or metabolic deterioration requires emergency treatment before the primary is found.

Investigation priorities

01
Core biopsy with immunohistochemistryFirst step

Confirm malignancy, lineage and a plausible organ profile while preserving tissue.

Management branches

StabiliseTreat urgent metastatic harm

The patient has neurological, obstructive, metabolic, haemorrhagic or infective compromise.

  1. Use ABCDE assessment and activate acute oncology plus the organ-specific emergency team before completing primary-site investigation.
  2. Obtain the targeted urgent imaging and begin indicated rescue, analgesia and thrombosis or infection management without awaiting every pathology addendum.
DefineComplete the initial CUP assessment

Metastatic malignancy is suspected and the patient is stable enough for investigation.

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Sources and review status4 sources · checked 27 Aug 2026 · clinical review pending
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

Authoring stateRapid draftClinical stateAwaiting reviewJurisdictionUnited Kingdom