# Re-test the metastasis, not the old primary, before every change of treatment

Source: https://onco.cc/ideas/idea-bio1-rebiopsy-before-switch/  
OnCo record `idea-bio1-rebiopsy-before-switch` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Treatment is often chosen from a biopsy taken years earlier from the original tumour. The spread disease may now look different. Test it again before switching drugs.

## Summary

Receptor and biomarker discordance between primary and metastasis is well documented (oestrogen receptor, HER2, PD-L1, and actionable alterations). Yet most line changes rely on archival tissue. The proposal is a payer-backed policy that a contemporaneous biopsy or validated liquid biopsy is offered before each line change in metastatic disease, with a registry to quantify how often the result changes therapy.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Contemporaneous re-testing changes the selected therapy in at least 15 percent of line changes and is cost-neutral or cost-saving through avoided ineffective treatment.
- Rationale: Discordance rates of 10 to 30 percent for key biomarkers are consistently reported; the rate of unnecessary or missed targeted therapy is a direct cost to payers.
- Proposed test: Coverage-with-evidence pilot in one health system: fund re-testing for 1,000 line changes, record decision changes and downstream costs over 18 months.
- Maturity: early-clinical
- Actor: payer

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- terms: [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)

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