Association Between Early PSA Increase and Clinical Outcome in Patients Treated with Enzalutamide for Metastatic Castration Resistant Prostate Cancer

Vincenza Conteduca, Simon J. Crabb, Emanuela Scarpi, Catherine Hanna, Francesca Maines, Helen Joyce, Paolo Fabbri, Lisa Derosa, Francesco Massari, Cristian Lolli, Sunnya Zarif, Robert J. Jones, Orazio Caffo, Tony Elliott, Ugo de Giorgi

Research output: Contribution to journalArticle

Abstract

Objective: 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. Patients and Methods: 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. Results: 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]. Conclusions: 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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalMolecular Diagnosis and Therapy
DOIs
Publication statusAccepted/In press - Mar 28 2016

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ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Medicine(all)
  • Pharmacology

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