Prostate-specific antigen dynamics predict individual responses to intermittent androgen deprivation.

Journal Article (Journal Article)

Intermittent androgen deprivation therapy (IADT) is an attractive treatment for biochemically recurrent prostate cancer (PCa), whereby cycling treatment on and off can reduce cumulative dose and limit toxicities. We simulate prostate-specific antigen (PSA) dynamics, with enrichment of PCa stem-like cell (PCaSC) during treatment as a plausible mechanism of resistance evolution. Simulated PCaSC proliferation patterns correlate with longitudinal serum PSA measurements in 70 PCa patients. Learning dynamics from each treatment cycle in a leave-one-out study, model simulations predict patient-specific evolution of resistance with an overall accuracy of 89% (sensitivity = 73%, specificity = 91%). Previous studies have shown a benefit of concurrent therapies with ADT in both low- and high-volume metastatic hormone-sensitive PCa. Model simulations based on response dynamics from the first IADT cycle identify patients who would benefit from concurrent docetaxel, demonstrating the feasibility and potential value of adaptive clinical trials guided by patient-specific mathematical models of intratumoral evolutionary dynamics.

Full Text

Duke Authors

Cited Authors

  • Brady-Nicholls, R; Nagy, JD; Gerke, TA; Zhang, T; Wang, AZ; Zhang, J; Gatenby, RA; Enderling, H

Published Date

  • April 9, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 1750 -

PubMed ID

  • 32273504

Pubmed Central ID

  • PMC7145869

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-15424-4

Language

  • eng

Conference Location

  • England