title: Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.
abstract: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.
  
  
  
  Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.
  
  
  
  Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.
  
  
  
  Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Bryce
authors.affiliation: OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Alumkal
authors.affiliation: Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: A
authors.identifier: 0000-0001-7012-1754
authors.initials: A
authors.lastname: Armstrong
authors.affiliation: Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: Department of Clinical Medicine, Rigshospitalet, Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
authors.forename: C N
authors.initials: CN
authors.lastname: Sternberg
authors.affiliation: Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Rathkopf
authors.affiliation: Department of Cancer Medicine, Institut Gustave-Roussy, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Division of Clinical Studies, Royal Marsden Hospital and Institute of Cancer Research, London, UK.
authors.forename: J
authors.identifier: 0000-0002-2034-595X
authors.initials: J
authors.lastname: de Bono
authors.affiliation: Division of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Medical Affairs, Medivation, Inc., San Francisco, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Abhyankar
authors.affiliation: Biostatistics, Medivation, Inc., San Francisco, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Lin
authors.affiliation: Medical Oncology, Astellas Pharma, Inc., Northbrook, IL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Krivoshik
authors.affiliation: Biostatistics, Astellas Pharma, Inc., Northbrook, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Phung
authors.affiliation: OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Beer
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen