Combined ctDNA and serum PSA for dynamic monitoring of metastatic prostate cancer starting first-line treatment: a prospective national cohort study

The prognosis of newly diagnosed metastatic prostate cancer is highly variable. The primary objective of the PARADIGM prospective cohort study was to evaluate predictors of survival in blood collected at the start of each of the first six treatment cycles from 114 patients with high-volume metastatic prostate cancer (biologically male) who were starting androgen deprivation therapy in combination with docetaxel or an androgen receptor pathway inhibitor. Here circulating tumor DNA (ctDNA) was detected in 29% of patients after 6-12 weeks of combination therapy (compared to 70% before any treatment) and associated with 12 month overall survival of 73% versus 99% for patients who were ctDNA-negative and 24 month survival of 50% versus 85%. The secondary objective was to test ctDNA with serum prostate-specific antigen (PSA). In multivariable models, both were independent risk factors on combination treatment with a hazard ratio of death of 20.34 for the poorest prognosis group, but only ctDNA was associated with shorter survival on androgen deprivation before the start of combination therapy. Using ctDNA with serum PSA and clinical characteristics can improve the accuracy of survival prediction and should be evaluated for ctDNA-informed treatment modification. ClinicalTrials.gov: NCT04067713 .