Circulating Tumor Cells as a Biomarker of Survival and Response to Radium-223 Therapy: Experience in a Cohort of Patients With Metastatic Castration-Resistant Prostate Cancer

Clin Genitourin Cancer. 2018 Dec;16(6):e1133-e1139. doi: 10.1016/j.clgc.2018.07.013. Epub 2018 Jul 21.

Abstract

Introduction: Although increasing numbers of therapies with proven survival benefits have become available for metastatic castration-resistant prostate cancer (mCRPC), including radium-223, there is still a need for reliable biomarkers that provide information about clinically meaningful outcomes and treatment responses.

Materials and methods: This study was a translational study that was conducted prospectively by the Spanish Oncology Genito-Urinary Group and included 45 patients with histologically confirmed mCRPC who were treated with radium-223. The primary response outcome was defined by a decline in circulating tumor cells (CTCs) of > 50% from baseline or a CTC count of ≤ 5 cells/7.5 mL at cycle 3 of radium-223. We also assessed response according to prostate-specific antigen and alkaline phosphatase levels. CTCs were evaluated as prognostic factor for treatment completion with radium-223 treatment. Kaplan-Meier estimates of survival were calculated for the global population and were correlated with biomarker response outcomes.

Results: Significantly, more patients with baseline CTC counts ≤ 5/7.5 mL, which are indicative of better prognoses, completed the 6 injections of therapy than those with CTC counts > 5 (16/22; 73% vs. 6/20; 30%, respectively; P = .012). The median overall survival was 16 months. Survival was significantly decreased in patients with baseline CTC counts > 5 cells/7.5 mL (7 months; P = .026) and baseline alkaline phosphatase levels ≥ 220 U/L (8 months; P = .028).

Conclusions: CTCs hold significant promise as a prognostic factor for survival and completing treatment prior to the initiation of bone-targeted radium-223 therapy. These findings may help to guide the use of radium-223 in patients with mCRPC.

Keywords: Biomarkers; Bone metastases; Circulating tumor cells; Radium-223; metastatic castration-resistant prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / blood
  • Bone Neoplasms / mortality
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary
  • Cell Count
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Injections, Intravenous
  • Male
  • Neoplastic Cells, Circulating / radiation effects*
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radiotherapy Dosage
  • Radium / administration & dosage*

Substances

  • Radium-223
  • Prostate-Specific Antigen
  • Radium