Carcinoma of unknown primary
A focused work-up for metastatic cancer with no obvious primary, the immunohistochemistry that points to a site, the favourable subsets treated like a known cancer, empirical chemotherapy for the rest, and where molecular profiling (CUPISCO) now fits.
Tier 2Condition
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- CUP is biopsy-proven metastatic cancer whose primary remains hidden after a standard work-up. It makes up about 2 to 3% of cancers and is still one of the more common causes of cancer death in Australia.
- Most are adenocarcinoma or poorly differentiated carcinoma. The primary, when it is eventually found, is most often lung or pancreas, then the biliary tree, stomach, kidney and bowel.
- The aim is not to find the primary at all costs. It is to find the treatable subsets (about 15 to 20%) and to get fit patients onto therapy quickly.
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Sources
- Optimal care pathway for people with cancer of unknown primaryAU/NZCancer Council Australia and Cancer Australia, 2020 (current edition, checked November 2026)
- eviQ Cancer Treatments Online (unknown primary protocols)AU/NZCancer Institute NSW
- Krämer A et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023;34:228-46European Society for Medical Oncology, 2023 (latest ESMO version, checked November 2026)
- Krämer A et al. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet 2024;404:527-39The Lancet, 2024
- Molecularly guided therapy versus continued chemotherapy in unfavorable cancer of unknown primary: updated efficacy and safety from the CUPISCO phase II study. J Clin Oncol 2026;44(30):2895-902 (erratum doi:10.1200/JCO-26-02285)Journal of Clinical Oncology, 2026
- Losa F et al. SEOM-GECOD clinical guideline for cancer of unknown primary (update 2025). Clin Transl Oncol 2026;28:1610-23Spanish Society of Medical Oncology, 2026
- NCCN Clinical Practice Guidelines in Oncology. Occult primaryNational Comprehensive Cancer Network, 2026
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Turnstile bot check on sign-in and signed-out feedback