Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: Data from Southwest Oncology Group trials 9346 (intergroup study 0162) and 9916

Maha H A Hussain, Bryan Goldman, Cathy Tangen, Celestia S. Higano, Daniel P. Petrylak, George Wilding, Atif M. Akdas, Eric J. Small, Bryan J. Donnelly, Subramanian Kanaga Sundram, Patrick A. Burch, Robert S. DiPaola, E. David Crawford

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

Purpose: Prostate-specific antigen progression (PSA-P) is an indicator of progression in hormone-sensitive (HS) and castration-resistant (CR) prostate cancer (PC). We evaluated different definitions of PSA-P as predictors of overall survival (OS). Patients and Methods: A total of 1,078 patients with HSPC who were on hormones (Southwest Oncology Group [SWOG] trial 9346 [S9346]) and 597 patients with CRPC who were treated with chemotherapy (SWOG trial 9916 [S9916]) were eligible for this analysis. PSA-P definitions tested included the following: PSA Working Group, Prostate Cancer Working Group (PCWG 2008), and other definitions. A time-varying approach analyzed associations between PSA-P at any time and OS. A landmark analysis examined the relationship between PSA-P status at 7 months for S9346, or 3 months for S9916, and subsequent OS. Results: In the time-varying analysis, both working groups definitions were strongly associated with OS (P < .001) in both study settings. In patients enrolled onto S9346, both definitions predicted a 2.4-fold increased risk of death (ROD) and a greater than four-fold increased ROD if PSA-P occurred in the first 7 months. In S9916, they predicted a 40% increase in ROD and a two-fold increase in ROD if PSA-P occurred at 3 months. In landmark analyses of patients on S9346 by using the PCWG 2008 definition of PSA-P, median subsequent OS was 10 months versus 44 months in patients who did or did not have PSA-P by 7 months, respectively; in S9916, data were 11 months versus 18 months for patients who did or did not have PSA-P by 3 months, respectively. Conclusion: PSA-P, defined as an increase of ≥ 25% greater than the nadir and an absolute increase of at least 2 or 5 ng/mL, predicts OS in HSPC and CRPC and may be a suitable end point for phase II studies in these settings.

Original languageEnglish (US)
Pages (from-to)2450-2456
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number15
DOIs
StatePublished - May 20 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hussain, M. H. A., Goldman, B., Tangen, C., Higano, C. S., Petrylak, D. P., Wilding, G., Akdas, A. M., Small, E. J., Donnelly, B. J., Sundram, S. K., Burch, P. A., DiPaola, R. S., & Crawford, E. D. (2009). Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: Data from Southwest Oncology Group trials 9346 (intergroup study 0162) and 9916. Journal of Clinical Oncology, 27(15), 2450-2456. https://doi.org/10.1200/JCO.2008.19.9810