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Original Investigation
July 2018

Phase 3 Assessment of the Automated Bone Scan Index as a Prognostic Imaging Biomarker of Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer: A Secondary Analysis of a Randomized Clinical Trial

Author Affiliations
  • 1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina
  • 2Division of Urology, Department of Surgery, Duke Cancer Institute, Duke University, Durham, North Carolina
  • 3Department of Pharmacology and Cancer Biology, Duke Cancer Institute, Duke University, Durham, North Carolina
  • 4EXINI Diagnostics AB, Lund, Sweden
  • 5Division of Urological Cancers, Department of Translational Medicine, Lund University, Malmö, Sweden
  • 6Department of Nuclear Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 7Umeå University, Umeå, Sweden
  • 8San Camillo Hospital, Rome, Italy
  • 9Forlanini Hospital, Rome, Italy
  • 10Indiana University School of Medicine, Indianapolis
  • 11Active Biotech AB, Lund, Sweden
  • 12Nordle Biostatistical Consultancy, Rydebäck, Sweden
  • 13The John Hopkins University School of Medicine, Baltimore, Maryland
  • 14Memorial Sloan Kettering Cancer Center, New York, New York
  • 15Weill Cornell Medicine, New York, New York
JAMA Oncol. 2018;4(7):944-951. doi:10.1001/jamaoncol.2018.1093
Key Points

Question  Is the automated Bone Scan Index an independent prognostic determinant of overall survival in men with metastatic castration-resistant prostate cancer?

Findings  In this secondary analysis of 721 participants in a randomized clinical trial, the automated Bone Scan Index was significantly associated with overall survival and remained independently associated with overall survival in a multivariable survival model. The automated Bone Scan Index was also significantly associated with additional clinical end points.

Meaning  This study supports the prognostic utility of the automated Bone Scan Index in the design and eligibility of clinical trials of systemic therapies for patients with metastatic castration-resistant prostate cancer.

Abstract

Importance  Prostate cancer commonly metastasizes to bone, and bone metastases are associated with pathologic fractures, pain, and reduced survival. Bone disease is routinely visualized using the technetium Tc 99m (99mTc) bone scan; however, the standard interpretation of bone scan data relies on subjective manual assessment of counting metastatic lesion numbers. There is an unmet need for an objective and fully quantitative assessment of bone scan data.

Objective  To clinically assess in a prospectively defined analysis plan of a clinical trial the automated Bone Scan Index (aBSI) as an independent prognostic determinant of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC).

Design, Setting, and Participants  This investigation was a prospectively planned analysis of the aBSI in a phase 3 multicenter randomized, double-blind, placebo-controlled clinical trial of tasquinimod (10TASQ10). Men with bone metastatic chemotherapy-naïve CRPC were recruited at 241 sites in 37 countries between March 2011 and August 2015. The statistical analysis plan to clinically evaluate the aBSI was prospectively defined and locked before unmasking of the 10TASQ10 study. The analysis of aBSI was conducted between May 25, 2016, and June 3, 2017.

Main Outcomes and Measures  The associations of baseline aBSI with OS, radiographic progression-free survival (rPFS), time to symptomatic progression, and time to opiate use for cancer pain.

Results  Of the total 1245 men enrolled, 721 were evaluable for the aBSI. The mean (SD) age (available for 719 men) was 70.6 (8.0) years (age range, 47-90 years). The aBSI population was representative of the total study population based on baseline characteristics. The aBSI (median, 1.07; range, 0-32.60) was significantly associated with OS (hazard ratio [HR], 1.20; 95% CI, 1.14-1.26; P < .001). The median OS by aBSI quartile (lowest to highest) was 34.7, 27.3, 21.7, and 13.3 months, respectively. The discriminative ability of the aBSI (C index, 0.63) in prognosticating OS was significantly higher than that of the manual lesion counting (C index, 0.60) (P = .03). In a multivariable survival model, a higher aBSI remained independently associated with OS (HR, 1.06; 95% CI, 1.01-1.11; P = .03). A higher aBSI was also independently associated with time to symptomatic progression (HR, 1.18; 95% CI, 1.13-1.23; P < .001) and time to opiate use for cancer pain (HR, 1.21; 95% CI, 1.14-1.30; P < .001).

Conclusions and Relevance  To date, this investigation is the largest prospectively analyzed study to validate the aBSI as an independent prognostic imaging biomarker of survival in mCRPC. These data support the prognostic utility of the aBSI as an objective imaging biomarker in the design and eligibility of clinical trials of systemic therapies for patients with mCRPC.

Trial Registration  ClinicalTrials.gov Identifier: NCT01234311

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