ctDNA Blood Test May Identify High-Risk mHSPC Before Treatment Begins

A blood test taken before starting treatment could help identify men with metastatic hormone-sensitive prostate cancer (mHSPC) who are at greater risk of developing treatment resistance early.

We have already discussed the importance of ctDNA after treatment in a previous article, but this new study looks at its potential value even before treatment begins.

A new prospective observational multicentre study enrolled 85 men with mHSPC, with 72 providing evaluable blood samples before starting androgen deprivation therapy (ADT). Circulating tumour DNA (ctDNA) was detectable in 46 patients, or 64%.

The difference in outcomes was substantial. Men with detectable ctDNA developed castration-resistant prostate cancer after a median of just 13 months. In men without detectable ctDNA, the median had not yet been reached. Detectable ctDNA was associated with a 3.43-times higher risk of progression to castration-resistant disease.

Overall survival showed a similar pattern. After a median follow-up of 20.8 months, median survival was 33 months among men with detectable ctDNA, while it had not yet been reached among those without detectable ctDNA. The risk of death was approximately 3.3 times higher in the ctDNA-positive group.

Men without detectable ctDNA were also more likely to achieve an undetectable PSA seven months after starting treatment, another indicator associated with better long-term outcomes.

However, ctDNA was strongly linked to the amount and presentation of disease. Among men with detectable ctDNA, 87% had metastatic disease at initial diagnosis and 80% had high-volume disease, compared with 39% and 46%, respectively, among men without detectable ctDNA. This means that part of the prognostic signal may reflect a greater overall tumour burden.

Even so, the researchers found indications that ctDNA could provide additional information within high-volume disease and among men receiving doublet treatment, although these smaller subgroup analyses need confirmation.

The findings add to growing evidence that ctDNA could complement PSA, scans and conventional disease-volume classifications in metastatic prostate cancer. Baseline ctDNA could potentially help establish how aggressive the disease is before treatment begins, while repeated ctDNA testing during therapy could eventually show how effectively that disease is responding.

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