Cancer types · Other solid tumours
Rare Cancers and Cancer of Unknown Primary
Cancer of unknown primary (CUP) is diagnosed when cancer has spread but the place it started cannot be identified after a thorough work-up. Rare cancers more generally have limited trial data and fewer specialists.
In both situations, comprehensive molecular profiling and multidisciplinary review can help organise the evidence, and some biomarkers carry evidence across tumour types.
Clinical and molecular questions that often arise
- Has the work-up for a primary site been completed?
- What do immunohistochemistry and molecular results suggest about the likely tissue of origin?
- Are there tumour-agnostic biomarkers, such as NTRK fusions or MSI-high status?
- Which trials might accept a rare or unknown-primary cancer?
Information that may be part of an individual assessment
- Imaging, which may include PET-CT.
- Biopsy with an extensive immunohistochemistry panel.
- Comprehensive genomic profiling, and in some cases gene-expression testing for tissue of origin.
Which investigations are appropriate is decided by the treating team for each person.
Molecular profiling and biomarker interpretation
Depending on the setting, molecular and biomarker questions in rare cancers and cancer of unknown primary may involve:
- Tumour-agnostic markers such as NTRK fusions, MSI-high or MMR-deficient status, high tumour mutational burden, BRAF V600E and RET fusions
- Site-suggestive alterations and expression patterns
Biomarkers, panels and available tests vary by subtype, disease setting, assay and guideline version. A detected alteration is not automatically actionable.
How KPCIRC pathways may apply
POAS
POAS may be especially relevant, because the six layers help organise many findings, distinguish tumour-agnostic evidence from tumour-specific evidence and record uncertainty transparently.
Molecular Tumour Board
MTB review is often valuable where the primary site is unclear and evidence must be weighed across specialties.
Second opinion and progression review
A second opinion may help confirm that the work-up is complete. Progression review can organise subsequent findings.
Hereditary risk and screening
Depending on the findings and family history, a hereditary assessment may sometimes be relevant.
How to access the relevant pathway
Patients and families
- Talk to your treating oncologist about whether an additional review may help.
- Request a consultation and tell us which question you want answered.
- Share records only when asked, through the secure route.
Referring doctors
- Define the clinical question and the pathway: POAS, MTB, second opinion or progression review.
- Start a case enquiry without patient identifiers.
- Scope, fees and timing are confirmed before any review proceeds.
Questions and limitations
What does “tumour-agnostic” mean?
It describes evidence that applies to a biomarker regardless of where the cancer started. Only a few biomarkers have this kind of evidence.
Can molecular testing find the primary site?
It can sometimes suggest a likely tissue of origin, but it does not always provide a definite answer.
Does this page apply to my situation?
This page is educational. It explains common questions but cannot account for individual circumstances. Your treating clinician is best placed to interpret your reports and plan your care.
Educational content reviewed against the KPCIRC service scope. It is not a diagnosis, a treatment recommendation or a statement that a specialist or service is available for this cancer type.