Radium-223 therapy of advanced metastatic castration-resistant prostate cancer: quantitative assessment of skeletal tumor burden for prognostication of clinical outcome and hematological toxicity

Aim: To investigate the prognostic value of quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223-dichloride ((223)RaCl2). We hypothesize that Bone Scan Index (BSI) can serve as a prognostic biomarker of overall survival (OS) and hematological toxicity, as well as a tool for response assessment in patients with mCRPC treated with (223)RaCl2Methods: Retrospective study of the Danish cohort of mCRPC patients who received (223)RaCl2 therapy between March 2014 and October 2015 and for whom a baseline bone scintigraphy was available. Bone scintigraphies were reviewed and graded according to extent of disease (EOD). Furthermore, automated BSI (EXINI BoneBSI by EXINI Diagnostics, Lund, Sweden), was obtained for baseline scintigraphies and follow-up scans after three cycles as well as at end of therapy (EOT). Clinical outcomes were OS and occurrence of haematological toxicity grade 2-5. Associations between BSI and clinical outcomes were investigated in multivariate regression models including visual assessment of bone scintigraphy and other relevant covariates. Results: A total of 88 patients were included. Median number of completed (223)RaCl2 cycles was four and 27 patients (31%) completed six cycles. BSI was significantly associated with OS in multivariate analysis and median OS for patients with BSI > 5 was 8.2 months vs. 15.0 months for patients with BSI ≤ 5 (Hazard ratio 2.65 [95% CI: 1.5-4.71]; P = 0.001). Likewise, baseline BSI was prognostic for occurrence of hematological toxicity and patients with BSI > 5 had an odds ratio of 3.02 (95% CI: 1.2-7.8; P = 0.02) for toxicity. BSI declined during therapy in 44% of patients who completed three cycles of (223)RaCl2 (n = 52) and in 84% of patients after EOT (n = 32). There was no significant association between change in BSI during therapy and OS. Conclusion: BSI is a promising biomarker for late-stage mCRPC patients receiving (223)RaCl2 for prognostication of OS and hematological toxicity. Further prospective studies are needed to evaluate the potential for BSI in response assessment of (223)RaCl2 therapy.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Sep 01 [Epub ahead of print]

Marie Øbro Fosbøl, Peter Meidahl Petersen, Andreas Kjaer, Jann Mortensen

Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine & PET., Rigshospitalet, Department of Oncology, Denmark., Rigshospitalet, Denmark.