title: Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer.
abstract: The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but is not validated as an intermediate endpoint for overall survival (OS).
  
  
  
  To evaluate the association between early PSA decline and OS following abiraterone acetate (AA) treatment.
  
  
  
  We identified mCRPC patients treated with AA before or after docetaxel at the Royal Marsden NHS Foundation Trust between 2006 and 2014. Early PSA decline was defined as a 30% decrease in PSA at 4 wk relative to baseline, and early PSA rise as a 25% increase.
  
  
  
  Association with OS was analyzed using multivariate Cox regression and log-rank analyses. Spearman's rho correlation coefficient (r) was calculated to evaluate the association between PSA changes at 4 wk and 12 wk.
  
  
  
  There were 274 patients eligible for this analysis. A 30% PSA decline at 4 wk was associated with longer OS (25.8 vs 15.1 mo; hazard ratio [HR] 0.47, p<0.001), and a 25% PSA rise at 4 wk with shorter OS (15.1 vs 23.8 mo; HR 1.7, p=0.001) in both univariate and multivariable models. The percentage PSA decline at 4 wk was significantly correlated with the percentage PSA change at 12 wk (r=0.82; p<0.001). Patients achieving a 30% PSA decline at 4 wk were 11.7 times more likely to achieve a 50% PSA decrease at 12 wk (sensitivity 90.9%, specificity 79.4%). Limitations include the retrospective design of this analysis.
  
  
  
  Patients not achieving 30% PSA decline after 4 wk of AA have a lower likelihood of achieving PSA response at 12 wk and significantly inferior OS. Prospective multicentre validation studies are needed to confirm these findings.
  
  
  
  Prostate-specific antigen (PSA) is commonly used to evaluate response to treatment in metastatic castration-resistant prostate cancer. Expert recommendations discourage reliance on PSA changes earlier than 12 wk after treatment initiation. Our data suggest that early PSA changes are associated with survival in patients receiving abiraterone acetate.
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Rescigno
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lorente
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Diletta
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kolinsky
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Sideris
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Zafeiris
authors.initials: Z
authors.lastname: Zafeiriou
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Semini
authors.initials: S
authors.lastname: Sumanasuriya
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Niven
authors.initials: N
authors.lastname: Mehra
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Jayaram
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Raquel
authors.initials: R
authors.lastname: Perez-Lopez
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Mateo
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Nina
authors.initials: N
authors.lastname: Tunariu
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Reid
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK. Electronic address: johann.de-bono@icr.ac.uk.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage*; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000077143:Docetaxel; D016903:Drug Monitoring / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D012042:Registries; D013223:Statistics as Topic; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate
keywords: Abiraterone acetate; Metastatic castration-resistant prostate cancer; Prostate-specific antigen