Abstract
We investigated whether inter-patient variation in the dynamic trajectory of hemoglobin (Hb), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prostate-specific antigen (PSA) can prognosticate overall survival (OS) in de novo mHSPC. This is a secondary analysis of the LATITUDE trial in which high-risk de novo mHSPC patients were randomly assigned to receive either androgen deprivation therapy (ADT) plus abiraterone or ADT plus placebo. We used a five-fold cross-validated joint model approach to determine the association of temporal changes in the serological markers with OS. Decision curve analysis was applied to determine the net benefit. When dynamic changes in Hb, LMR, NLR, PLR, and PSA were included in a multivariate joint model, an increase in the log of the current value of PSA (HR: 1.24 [1.20-1.28]) was associated with inferior OS. A multivariate joint model that captured dynamic trajectory of Hb, NLR, PLR, LMR, and PSA up to 24 months, showed a net benefit over the "treat all" strategy at a threshold of probability of approximately ≥30% while no net benefit was seen when dynamic change in PSA was omitted. Our joint model could be used for designing future adaptive trials investigating sequential treatment personalization.