title: Poor concordance between CA-125 and RECIST at the time of disease progression in patients with platinum-resistant ovarian cancer: analysis of the AURELIA trial.
abstract: Data on CA-125 as a predictor of disease progression (PD) in ovarian cancer come predominantly from patients with platinum-sensitive disease receiving chemotherapy alone. We assessed concordance between CA-125-defined and RECIST-defined PD using data from the Gynecologic Cancer InterGroup (GCIG) randomized phase III AURELIA trial in platinum-resistant ovarian cancer (PROC).
  
  
  
  Patients with PROC were randomized to receive single-agent chemotherapy with or without bevacizumab. PD by CA-125 was defined according to GCIG criteria (except that confirmatory CA-125 measurement was not required). This exploratory analysis included patients with RECIST PD and a CA-125 reading ≤28 days before and ≤21 days after RECIST-defined PD.
  
  
  
  Of 218 eligible patients, only 94 (43%, 95% confidence interval 36% to 50%) had concordant RECIST and CA-125 PD status (42% in the chemotherapy-alone arm; 45% in the bevacizumab combination arm, P = 0.6). There was no evidence of CA-125-defined PD in the remaining 124 patients despite PD according to imaging. There were no significant differences in baseline characteristics between patients with PD defined by both RECIST and CA-125 and those with RECIST-only PD. CA-125 was even less sensitive in detecting PD in patients with early (<8 weeks after randomization) compared with later RECIST-defined PD (69% versus 53%, respectively, not meeting CA-125 criteria; P = 0.053). There was no significant difference in survival after PD in patients with concordant PD by RECIST and CA-125 versus those with PD only by RECIST. We validated our findings in an independent study population of PROC.
  
  
  
  In this platinum-resistant population, PD was typically detected earlier by imaging than by CA-125, irrespective of bevacizumab treatment. Disease status by CA-125 at the time of PD was not prognostic for overall survival. Regular radiologic assessment as well as symptom benefit assessment should be considered during PROC follow-up.
authors.affiliation: NSGO and Department of Gynecological Cancer, The Norwegian Radium Hospital, Oslo University Hospital, Oslo stinalindemann@hotmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Lindemann
authors.affiliation: NSGO and Department of Gynecological Cancer and Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital and Institute for Clinical Medicine, Oslo University, Oslo, Norway.
authors.forename: G
authors.initials: G
authors.lastname: Kristensen
authors.affiliation: NSGO and Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: M R
authors.initials: MR
authors.lastname: Mirza
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Davies
authors.affiliation: AGO and Oncological Center, Hospital Jerusalem, Hamburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hilpert
authors.affiliation: GEICO and Valencia Institute of Oncology, Valencia, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Romero
authors.affiliation: GINECO and Baskent University, Ankara, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Ayhan
authors.affiliation: AGO and Department of Gynecology and Obstetrics, Hospital of University of Munich, Campus Großhadern, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Burges
authors.affiliation: GEICO and University Hospital Queen Sofía, Córdoba, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Rubio
authors.affiliation: MITO and National Tumour Institute of Milan, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Raspagliesi
authors.affiliation: BGOG and Antwerp University Hospital, Edegem, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Huizing
authors.affiliation: DGOG and Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: G-J
authors.initials: GJ
authors.lastname: Creemers
authors.affiliation: HECOG and University of Athens, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Lykka
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia.
authors.forename: C K
authors.initials: CK
authors.lastname: Lee
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Gebski
authors.affiliation: GINECO and Paris Descartes University, AP-HP Central Paris University Hospitals, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Pujade-Lauraine
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D018394:CA-125 Antigen / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D010984:Platinum / Q000627:therapeutic use; D011379:Prognosis; D066066:Response Evaluation Criteria in Solid Tumors
chemical_list: D018394:CA-125 Antigen; D000068258:Bevacizumab; D010984:Platinum; D004317:Doxorubicin
keywords: CA-125; RECIST; ovarian cancer; platinum resistance