# Molecular indolence classifiers bundled with every screening programme

Source: https://onco.cc/ideas/idea-moon-indolence-classifiers-with-screening/  
OnCo record `idea-moon-indolence-classifiers-with-screening` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Screening finds cancers that would never have caused harm alongside dangerous ones. Pair every screening test with a test that says which is which, so people with harmless findings can safely watch and wait.

## Summary

Overdiagnosis in prostate, thyroid, breast (DCIS) and low-dose CT lung screening leads to unnecessary surgery and anxiety and is the main argument against expanding screening. Molecular and imaging classifiers of indolence (genomic classifiers in prostate cancer, DCIS risk scores, radiomic and growth-rate models for lung nodules, ctDNA fragmentomics) are emerging but not integrated into programmes. The proposal is that every screening programme develops, validates and deploys an indolence classifier with a surveillance-first protocol for low-risk findings, and reports overdiagnosis as a monitored quality metric.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Classifier-guided surveillance-first protocols reduce treatment of screen-detected indolent lesions by half without increasing interval cancers or cancer-specific mortality.
- Rationale: Active surveillance in low-risk prostate cancer already shows that deferring treatment is safe when risk is classified well; making classification part of the programme extends the benefit and the political viability of screening.
- Proposed test: Randomised trial within a screening programme of classifier-guided surveillance-first versus standard management for low-risk findings; primary endpoint treatment rate, secondary interval cancers and mortality at ten years.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010): https://doi.org/10.1093/jnci/djq099

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- technologies: [AI in radiology](https://onco.cc/technologies/radiology-ai-screening/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- terms: [Stage shift](https://onco.cc/terms/stage-shift/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Overdiagnosis and false alarms](https://onco.cc/bottlenecks/b-overdiagnosis/), [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/)
- key papers: [Overdiagnosis in cancer](https://onco.cc/key-papers/paper-welch-j-natl-cancer-inst/)

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