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  • Original Article
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Clinical Research

Radium-223 outcomes after multiple lines of metastatic castration-resistant prostate cancer therapy in clinical practice: implication of pre-treatment spinal epidural disease

Prostate Cancer and Prostatic Diseases volume 19, pages 271–276 (2016)Cite this article

Subjects

Abstract

Background:

Magnetic resonance imaging (MRI) is not routinely performed before initiating radium-223 to document spinal epidural disease. However, radium-223 decays to form α-particles with very short path lengths that may not reach the epidural space. Herein, we investigate the impact of baseline spinal epidural disease on metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223.

Methods:

Between October 2013 to December 2014, 41 consecutive mCRPC patients at a large tertiary cancer center were prescribed radium-223 as part of standard of care. 29% of patients had pre-treatment epidural disease (posMRI), 27% had no epidural disease (negMRI), and 44% did not have a baseline MRI (noMRI). All patients had post-treatment spinal imaging. Actuarial survival times were calculated for overall survival (OS), spinal axis radiographic progression-free survival (spinePFS) and epidural progression-free survival (epiPFS) from time of first radium-223 treatment.

Results:

For patients with posMRI (n=12), noMRI (n=18) and negMRI (n=11) cumulative rates of development or worsening of epidural disease and/or high-grade cord compression at time of last follow-up were 83%, 44% and 9%, respectively (P=0.001). For the posMRI, noMRI and negMRI groups the median OS was 6.3 months, 12.6 months and not reached (P=0.01), the median spinePFS was 3.2 months, 4.8 months and not reached (P=0.01), and the median epiPFS was 3.2 months, 10.4 months and not reached (P=0.001). Completing less than six cycles of radium-223 was significantly associated with worse OS (P<0.0001), spinePFS (P=0.007) and epiPFS (P=0.01). Greater than or equal to twenty osseous lesions pre-treatment was significantly associated with worse spinePFS (P=0.001) and epiPFS (P=0.03).

Conclusions:

In a heavily pre-treated small cohort, patients with baseline epidural disease frequently progressed to spinal cord compression and early cessation of radium-223 therapy. Studies are needed to determine the optimal timing of radium-223 with other mCRPC therapies given the predilection for epidural disease and treatment failure after multiple prior lines of mCRPC therapy.

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Acknowledgements

Supported by the Prostate Cancer Foundation Rebecca and Nathan Milikowsky Young Investigator Award (DES). MJM and JRO have received funding and are conducting a clinical trial with Bayer.

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Author notes

  1. D E Spratt and J R Osborne: Co-first authorship.

Authors and Affiliations

  1. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    D E Spratt, Z S Zumsteg, J Leeman, A Rivera & M J Zelefsky

  2. Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI, USA

    D E Spratt

  3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    J R Osborne & K Rebeiz

  4. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    M J Morris

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  1. D E Spratt
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Correspondence to D E Spratt.

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Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

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Spratt, D., Osborne, J., Zumsteg, Z. et al. Radium-223 outcomes after multiple lines of metastatic castration-resistant prostate cancer therapy in clinical practice: implication of pre-treatment spinal epidural disease. Prostate Cancer Prostatic Dis 19, 271–276 (2016). https://doi.org/10.1038/pcan.2016.14

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