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How much of the DNA floating in a blood sample came from the cancer. Above a few per cent, a plasma test finds what a biopsy would find; below it, a negative result means the test could not see, not that there is nothing there.
The number that decides whether a plasma genomic result can be believed. In 45 men with metastatic castration-resistant prostate cancer whose plasma was taken on the day of a metastatic tissue biopsy, 75.6% of samples had a circulating tumour DNA proportion above 2% of total cell-free DNA; in those samples, every somatic mutation found in the matched tissue was also present in plasma, the ranking of variant allele fractions was closely similar, and copy-number calls in actionable genes agreed 88.9% of the time (Wyatt 2017). At scale, 3,129 of 3,334 men with advanced prostate cancer, 94%, had detectable circulating tumour DNA at a median tumour fraction of 7.5%, and 67 of the 72 BRCA1 or BRCA2 mutations found in tissue were also found in plasma, 93%, including 100% of the variants predicted to be germline (Tukachinsky 2021). Two things confound the reading. Tumour fraction tracks disease burden, so plasma performs worst in the low-volume disease where an early answer would help most. And clonal haematopoiesis contributes variants that look somatic: at a 2% threshold, 13 of 69 men had such variants, and 7, 10%, had one in a gene used to decide PARP inhibitor candidacy, most often ATM, with clonal haematopoiesis accounting for almost half of all somatic repair-gene variants detected (Jensen 2021).
A blood test for cancer genes is easier than a bone biopsy and often gives the same answer. If it comes back with nothing found, that is not the same as nothing being there: it can mean the cancer was not shedding enough DNA into the blood that day, and a tissue sample may still be needed.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
The estimated proportion of cell-free DNA in plasma that derives from tumour, reported with the genomic result; below the assay's tumour-fraction floor a negative result is uninformative rather than negative, and any repair-gene variant used for treatment selection should be checked against a paired whole-blood control.
“Seventy-five point six percent of cfDNA samples had a ctDNA proportion greater than 2% of total cfDNA. In these patients, all somatic mutations identified in matched metastatic tissue biopsies were concurrently present in ctDNA.”
Wyatt et al., Journal of the National Cancer Institute 2017No approval uses this readout as a threshold. It is defined by Tukachinsky et al., Clin Cancer Res 2021: circulating tumour DNA profiling in 3,334 men with advanced prostate cancer.
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.
It shows that the useful information in a castration-resistant plasma sample is in the repair genes and TP53 rather than in the androgen receptor finding that dominates the report, and it is the closest thing the field has to a head-to-head comparison of abiraterone against enzalutamide.
It is the study that justified using plasma instead of a bone biopsy in this disease, with the honest caveat attached: the concordance holds only above a tumour fraction threshold, and below it the test is uninformative rather than negative.
Shares Androgen receptor, Comprehensive genomic profiling, Prostate cancer and the tags biomarker, prostate.
Shares Androgen receptor, Comprehensive genomic profiling, Prostate cancer and the tags biomarker, prostate.
Shares AR amplification (gene and upstream enhancer), Androgen receptor, Metastatic castration-resistant prostate cancer, Prostate cancer and the tags biomarker, prostate.
Shares Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms, AR amplification (gene and upstream enhancer), Androgen receptor, Circulating tumour DNA (ctDNA) and the tag biomarker.
Shares AR amplification (gene and upstream enhancer), Biopsy, Androgen receptor, Metastatic castration-resistant prostate cancer and the tag biomarker.
Shares Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA) and the tag biomarker.
Shares Biopsy, Clonal evolution & minimal residual disease, Comprehensive genomic profiling, Liquid biopsy (ctDNA) and the tag biomarker.
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Homologous recombination repair gene mutation in prostate cancer, Germline vs somatic mutations, BRCA1 / BRCA2 (HRD) and the tag biomarker.