Fig. 4: ctDNA fraction is independently associated with mCRPC treatment outcomes.

Kaplan-Meier estimates of time from initiation of first-line systemic therapy for mCRPC to death or last follow-up (A + D) and PSA progression-free survival on first-line therapy (B + E) stratified by synchronously-measured ctDNA% dichotomized by median (A + B) or by predefined bins (high, low, undetectable) (D + E)—see Supplementary Data 2 for per-patient ctDNA% values. Shading indicates 95% confidence intervals; in-set tables show univariable hazard ratios (HRs) from a Cox proportional hazards model. Forest plots show HRs and 95% confidence intervals from univariable (C) and multivariable (F) Cox proportional hazard regression models incorporating ctDNA% plus additional clinical prognostic markers. G Waterfall plot showing best PSA response (relative to baseline PSA) on first-line mCRPC therapy stratified by baseline ctDNA% (ctDNA > 30%, ctDNA 2-30%, and ctDNA < 2%). P-values (two-sided) reflect Fisher’s Exact Test’s comparing the proportion of patients achieving a ≥50% PSA response across ctDNA categories. H Evidence for a nonlinear relationship between ctDNA% and risk of death. Univariable Cox proportional HRs (plotted as dots) for overall survival from initiation of first-line mCRPC therapy as a function of ctDNA% partitioned into non-overlapping intervals. Each interval is demarcated by the horizontal gray lines, with the center of each ctDNA% interval used as each datapoint’s x-coordinate. Vertical gray lines show individual intervals’ 95% HR confidence intervals. For all comparisons, the reference group is patients with ctDNA < 2%; marker size is proportional to the number of patients in the non-reference group (per-interval n is provided in the Source Data file). Solid red line shows a three-parameter negative exponential (with upper asymptote) curve fit. See Supplementary Data 4–6 for a complete summary of univariable and multivariable Cox proportional hazard regression model statistics, per-endpoint event rates, and summary of missing clinical data per initiating line of therapy. Correction for multiple hypothesis testing was not performed. REF reference.