title: Association Between Early PSA Increase and Clinical Outcome in Patients Treated with Enzalutamide for Metastatic Castration Resistant Prostate Cancer.
abstract: Prostate-specific antigen (PSA) decline by 50 % from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the association between PSA changes at 4 weeks and clinical outcome.
  
  
  
  Eligible patients had PSA levels assessed at baseline, and monthly during enzalutamide treatment. Early PSA increase was defined as an increased PSA level at 4 weeks ≥20 % (PSA + 20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥30 % (PSA30w4) and ≥50 % (PSA50w4) from baseline. Progression-free survival (PFS), overall survival (OS) and their 95 % confidence intervals (CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. The impact of early PSA increase and decline on PFS and OS was evaluated by Cox regression analyses.
  
  
  
  We assessed 193 patients with median age of 73 years (range 43-91 years). The median follow-up was 11.7 months (range 0.5-27.4 months). PSA + 20w4 predicted both PFS and OS [HR 6.50 (95 % CI 2.63-16.07; p < 0.0001) and HR 10.54 (95 % CI 4.02-27.64; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95 % CI 0.21-0.67; p = 0.0009) and HR 0.34 (95 % CI 0.19-0.60; p = 0.0003), respectively].
  
  
  
  An early PSA increase, defined as a PSA level at 4 weeks ≥20 % (PSA + 20w4), could be useful to quickly identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA + 20W4 as an early biomarker of primary resistance to enzalutamide.
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Conteduca
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Crabb
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Beatson West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hanna
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Maines
authors.affiliation: Christie Hospital, Manchester, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Joyce
authors.affiliation: Oncology Unit, Cervesi Hospital, Cattolica, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fabbri
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Pisa, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Derosa
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Lolli
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Sunnya
authors.initials: S
authors.lastname: Zarif
authors.affiliation: Beatson West of Scotland Cancer Centre, Glasgow, UK.|Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Caffo
authors.affiliation: Christie Hospital, Manchester, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Elliott
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy. ugo.degiorgi@irst.emr.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen