# Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Source: https://onco.cc/key-papers/paper-esmo-cancer-of-unknown-primary-guideline-ann-oncol-2023/  
OnCo record `paper-esmo-cancer-of-unknown-primary-guideline-ann-oncol-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The European guideline on cancer that has spread from a primary no one can find: how far to look, which favourable subsets to treat like a known cancer, and what chemotherapy or targeted therapy to give the rest.

## Summary

ESMO guideline defining cancer of unknown primary, the recommended diagnostic work-up (histology, immunohistochemistry, CT, PET-CT in selected cases, and comprehensive genomic profiling), the favourable subsets (such as women with peritoneal serous carcinoma, isolated axillary adenocarcinoma, squamous carcinoma in cervical nodes, poorly differentiated carcinoma with midline distribution, and neuroendocrine carcinoma) that are treated as their presumed primary, and empirical platinum-based chemotherapy for unfavourable disease with molecularly guided therapy where an actionable alteration is found.

## Fields

- Kind: Key paper
- Last checked: 2026-09-18
- Journal: Annals of Oncology
- Year: 2023
- DOI: 10.1016/j.annonc.2022.11.013
- Authors: Krämer A, Bochtler T, Pauli C, et al.
- What it means: The split between favourable and unfavourable cancer of unknown primary on OnCo, and the treatment on each page, follow this guideline.
- Caveats: Published shortly before the CUPISCO result; the place of molecularly guided therapy is still being defined.; Tissue-of-origin gene expression tests are not recommended for routine treatment selection.

## Sources

- Ann Oncol 2023: https://doi.org/10.1016/j.annonc.2022.11.013
- PubMed: https://pubmed.ncbi.nlm.nih.gov/36563965/

## Connected records

- cancers: [Cancer of unknown primary, favourable subsets](https://onco.cc/cancers/cup-favourable-subsets/), [Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)](https://onco.cc/cancers/cup-unfavourable/)
- journals: [Annals of Oncology](https://onco.cc/journals/annals-of-oncology/)

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