Loading
Nearly one man in eight with prostate cancer that has spread carries an inherited fault in a DNA repair gene, most often BRCA2. Family history and age at diagnosis did not predict who: the only way to find them is to test everybody.
Colin Pritchard, Peter Nelson, Joaquin Mateo and colleagues recruited 692 men with documented metastatic prostate cancer, unselected for family history or age at diagnosis, and used multiplex sequencing to look for germline mutations in 20 DNA repair genes associated with autosomal dominant cancer predisposition syndromes.
The result is one of the cleanest arguments for universal testing in oncology. The mutation frequency was 11.8 percent in metastatic disease against 4.6 percent in 499 men with localised disease and 2.7 percent in 53,105 people in the Exome Aggregation Consortium without a known cancer diagnosis, and it did not differ according to whether there was a family history of prostate cancer or according to age at diagnosis. A selective testing policy based on family history would therefore miss most carriers.
The evidence that made germline testing standard for every man with metastatic prostate cancer, whatever his family history. It changes his treatment, because PARP inhibitors and platinum work better in these tumours, and it changes his relatives' screening, because BRCA2 carries breast, ovarian and pancreatic risk as well.
The randomised proof for PARP inhibition in BRCA-altered prostate cancer, and the clearest evidence that the homologous recombination repair gene list should not be used as a single yes-or-no test. ATM-altered disease needs a different answer, and does not yet have one.
The evidence base for setting the age at which screening starts by risk rather than by birthday. It is also a warning: the same score performs differently across ancestries, so a risk model built and validated in European cohorts will under-serve the men at highest risk.
The genomic definition of advanced prostate cancer, and the evidence that made molecular testing standard in it. The 19.3 percent DNA repair figure is the direct ancestor of PROfound, TRITON3, PROpel and TALAPRO-2, and the 8 percent germline figure is why a tumour result in this disease has implications for a man's relatives.
The first molecularly stratified treatment in prostate cancer, and the proof that the synthetic lethality that works in ovarian and breast cancer works here too. Every PARP inhibitor now licensed in prostate cancer traces back to this trial.
Shares TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer, TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Homologous recombination deficiency (HRD) and the tag prostate-evidence.
Shares TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, SU2C-PCF: integrative clinical genomics of advanced prostate cancer, Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Homologous recombination deficiency (HRD) and the tag prostate-evidence.
Shares SU2C-PCF: integrative clinical genomics of advanced prostate cancer, Homologous recombination deficiency (HRD), Next-generation sequencing (NGS), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.
Shares Next-generation sequencing (NGS), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Biomarkers are not validated or standardised, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares SU2C-PCF: integrative clinical genomics of advanced prostate cancer, Next-generation sequencing (NGS), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction, Metastatic hormone-sensitive prostate cancer, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Fragmented care and guideline gaps and the tag prostate-evidence.
Shares Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Fragmented care and guideline gaps, Prostate cancer and the tag prostate-evidence.
Shares Metastatic hormone-sensitive prostate cancer, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Metastatic castration-resistant prostate cancer, Prostate cancer and the tag prostate-evidence.