How We Evaluate Cancer Testing Technology
Not every test is right for every person. Not every test is right at all.
The cancer testing landscape is expanding faster than the evidence behind it. New screening products enter the market regularly, each with their own claims, limitations, and appropriate use cases.
The PreOncology Evidence Grading Framework
Before any technology is incorporated into a member’s surveillance plan, it is evaluated against the PreOncology Evidence Grading Framework, a composite scoring system developed and maintained by the PreOncology Institute. The framework scores each technology across multiple clinical dimensions. Technologies that do not meet the standard are not used.
Framework Dimensions
Efficacy Evidence
Harm Profile
Testing Characteristics
Clinical Utility
The Technologies We Orchestrate
Category 1
Risk Stratification
Identifies who is most likely to benefit from intensified prevention and surveillance. These tests establish the genomic foundation of each member’s risk profile and inform lifetime surveillance decisions.
Whole Genome Sequencing
The most comprehensive genomic sequencing test available. Whole genome sequencing assesses more than three billion base pairs across the genome, providing broad germline variant assessment across coding and non-coding regions. Unlike targeted panel testing, whole genome sequencing captures a wide spectrum of variant types, including rare variants, structural rearrangements, and copy number changes, while enabling identification of potentially pathogenic variants that panels are not designed to detect. The result is one of the richest, most complete genomic risk pictures available from a single genomic assay.
Category 2
Early Biological Signal Detection
Detects molecular evidence that cancer or premalignant biology may be present before conventional diagnosis. These are the tests that can find what standard screening was never designed to look for.
ctDNA Mutation Assays
Detect circulating tumor DNA in the bloodstream by identifying somatic mutations carried by cancer cells. Widely used in advanced cancer to monitor treatment response and increasingly applied in early detection settings.
cfDNA Methylation Assays
Detect aberrant DNA methylation patterns in cell-free DNA circulating in the blood. Methylation changes occur early in malignant transformation, often before mutations accumulate. Can identify cancer-associated signals across multiple tumor types simultaneously.
Protein Biomarker Panels
Blood-based tests measuring circulating proteins secreted by cancer cells or released in response to tumor activity. Individual markers such as PSA, CA-125, AFP, and CEA have been used clinically for decades. More recent panels combine multiple proteins to improve sensitivity and specificity.
Multi-Cancer Early Detection (MCED) Tests
Commercial blood tests designed to detect signals from multiple cancer types simultaneously. Typically combine cfDNA methylation profiling, mutation detection, and tissue-of-origin prediction.
Fragmentomics
Analysis of the physical characteristics of cell-free DNA fragments, including their length, end motifs, and nucleosome positioning patterns. Cancer cells release DNA fragments with distinctive fragmentation signatures. Does not require identification of specific mutations and can detect signals from cancers with low mutational burden.
Autoantibody Signatures
Detection of antibodies the immune system produces in response to tumor-associated antigens. Because autoantibodies can be generated months to years before a tumor becomes radiographically detectable, they represent a potentially early detection window.
RNA / miRNA Assays
Tests measuring messenger RNA or microRNA circulating in the blood as indicators of active gene expression in cancer cells.
Multi-Omics Blood Tests
Platforms that simultaneously analyze multiple molecular data types from a single blood sample to produce an integrated cancer signal. The premise is that combining signals across molecular layers improves sensitivity and specificity beyond what any single modality can achieve.
Category 3
Localization
When a signal is detected, these tests help determine where it is coming from. Localization is the critical bridge between a positive early detection signal and a defined clinical response.
Tissue-of-Origin Classifiers
Algorithms that analyze the molecular signature of a cancer signal to predict the organ or tissue type where a tumor is most likely located. Because cfDNA carries epigenetic marks from the cells that shed it, methylation classifiers can infer which organ contributed the signal. A key component of MCED tests.
Organ-Specific Biomarker Panels
Targeted tests using established organ-specific biomarkers following detection of a non-specific signal to narrow the probable site of malignancy. These tests leverage decades of validated biomarker data to guide clinical decision-making after a multi-cancer or non-specific early detection finding.
Category 4
Imaging
Directly visualizes cancer or precursor lesions. Imaging tests are selected and sequenced based on each member’s risk profile, not applied uniformly across the population.
Whole-Body MRI
Magnetic resonance imaging of the entire body in a single examination, without ionizing radiation. Particularly sensitive for detecting soft tissue malignancies, lymphomatous involvement, and bone marrow infiltration.
Organ-Specific MRI
Targeted MRI protocols optimized for the anatomy and pathology of a specific organ, offering higher resolution and sensitivity than whole-body sequences. Examples include multiparametric MRI of the prostate, breast MRI, and liver MRI with hepatobiliary contrast. The imaging standard of care in several cancer screening contexts.
Low-Dose CT (LDCT)
CT performed at a fraction of the standard radiation dose, optimized for detecting early-stage lung cancer. The only imaging-based cancer screening test with Level A evidence from a randomized controlled trial demonstrating mortality reduction.
Mammography / Tomosynthesis
X-ray-based imaging of breast tissue. Digital breast tomosynthesis captures multiple images at different angles to construct a three-dimensional reconstruction, reducing tissue overlap and improving detection of invasive cancers, particularly in women with dense breast tissue. Has largely replaced 2D mammography at major screening centers.
Ultrasound
Imaging using high-frequency sound waves to generate real-time images of soft tissue structures. Used to characterize breast masses, evaluate thyroid nodules, assess liver and abdominal organs, and guide biopsies. Free of ionizing radiation and widely available as a practical adjunct in multi-modality screening programs
PET/CT and PET/MRI
Hybrid imaging platforms combining functional metabolic data with anatomic detail. PET detects the preferential uptake of radiolabeled tracers by metabolically active cancer cells. Standard of care for staging many cancers and evaluating treatment response. PET/MRI offers superior soft tissue resolution with lower radiation exposure.
Radiomics and AI-Assisted Imaging
Extraction and analysis of quantitative features from radiologic images using machine learning algorithms to improve diagnostic accuracy and reduce false positives and negatives. AI-assisted reading tools have received FDA clearance for mammography, chest CT for lung nodule characterization, and prostate MRI interpretation.
Advanced Endoscopic Imaging
gh-definition and technology-enhanced endoscopic techniques that improve visualization of mucosal lesions in the gastrointestinal tract, airways, and bladder. Integral to upper and lower GI cancer surveillance programs. Techniques include narrow-band imaging, chromoendoscopy, and endoscopic ultrasound.
The PreOncology Program Difference
No single test is a program. What separates PreOncology from a testing company is the clinical infrastructure that determines which test is right for which person, at which point in time, interpreted within the context of everything else that is known about that individual.
