For a paper in Clinical Chemistry, a team from Denmark, Sweden, and Belgium describe survival insights that can be gained through low-coverage sequencing of circulating tumor DNA (ctDNA) in individuals with metastatic, castration-resistant prostate cancer (mCRPC). The investigators used their low-pass whole-genome sequencing (LPWGS) approach to assess cell-free DNA (cfDNA) in 200 blood samples from 143 mCRPC patients receiving first-line treatment with androgen signaling inhibitors. There, they found that higher pre-treatment ctDNA levels were linked to more limited prostate specific antigen marker responses to treatment and shorter progression-free and overall survival. Similarly, the authors note that elevated levels of copy number alterations found in baseline ctDNA tended to correspond to poor outcomes, with copy number alterations typically increasing during disease progression. Together, they say, the findings suggest that "LPWGS of plasma cfDNA holds clinical potential for outcome prognostication in mCRPC patients through estimation of ctDNA [percentage] and tumor [copy number alteration] patterns," the authors report, adding that "our findings are consistent with previous tissue-based reports showing that a high [copy number alteration] burden in prostate tumor tissue is associated with significantly shorter biochemical recurrence-free and cancer-specific survival in localized and metastatic [prostate cancer], respectively."
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