Small Bowel Cancer
Small bowel adenocarcinoma is uncommon and often diagnosed late because its symptoms are non-specific. Its molecular profile sits between that of colorectal and gastric cancer without being identical to either.
Disease categories
Major disease categories
- Small bowel adenocarcinoma
- Duodenal adenocarcinoma
- Small bowel neuroendocrine tumours
- Small bowel lymphoma
Molecular
Molecular considerations
Mismatch repair deficiency occurs at an appreciable rate. KRAS, APC, SMAD4 and ERBB2 alterations are described. The rate of mismatch repair deficiency makes testing for it a routine part of the discussion.
Markers commonly discussed in small bowel cancer
- MMR / MSI
- KRAS
- ERBB2
- BRAF
- TMB
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Comprehensive profiling is frequently discussed given how thin the disease-specific evidence base is.
Germline
Germline considerations
Lynch syndrome is a genuine consideration, as is Peutz-Jeghers syndrome where the phenotype suggests it.
Molecular monitoring
ctDNA and liquid biopsy considerations
Investigational in this disease.
Single-cell & computation
Single-cell and algorithmic approaches
In gastrointestinal and hepatobiliary disease, single-cell sequencing is used chiefly to characterise the tumour microenvironment and to resolve clonal structure in tumours that are heterogeneous between regions. Single-cell DNA analysis helps establish whether a RAS or driver alteration is clonal or subclonal, which bears directly on how much weight it should carry. Algorithm work here includes molecular residual disease detection from serial samples, mismatch repair classification from sequencing data, and pipelines that reconcile findings across multiple biopsy sites.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has mismatch repair status been established?
- Has an underlying predisposing condition such as coeliac disease or Crohn disease been considered?
- Is the histology confirmed as adenocarcinoma rather than a neuroendocrine tumour?
Resistance
Resistance and recurrence questions
- Has the molecular profile been reassessed after progression?
Trials
Clinical trial considerations
Given the small evidence base, basket trials and tissue-agnostic options are particularly relevant.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.