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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References
Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD . et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369: 213–223.
Cabot RC, Harris NL, Rosenberg ES, Shepard J-AO, Cort AM, Ebeling SH et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012; 367: 1187–1197.
de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels J-P, Kocak I et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010; 376: 1147–1154.
De Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364: 1995–2005.
Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411–422.
Gillessen S, Omlin A, Attard G, de Bono J, Efstathiou E, Fizazi K et al. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann Oncol 2015; 26: 1589–1604.
Mohler J, Armstrong A, Bahnson R . NCCN clinical practice guidelines for prostate cancer. J Natl Compr Canc Netw 2015; 8: 162–200.
Buhmann S, Becker C, Duerr HR, Reiser M, Baur-Melnyk A . Detection of osseous metastases of the spine: comparison of high resolution multi-detector-CT with MRI. Eur J Radiol 2009; 69: 567–573.
Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE et al. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 2004; 63: 940–945.
Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 2000; 31: 578–583.
Janjan NA . Radiation for bone metastases. Cancer 1997; 80: 1628–1645.
Lutz S, Berk L, Chang E, Chow E, Hahn C, Hoskin P et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys 2011; 79: 965–976.
Gunawardana DH, Lichtenstein M, Better N, Rosenthal M . Results of strontium-89 therapy in patients with prostate cancer resistant to chemotherapy. Clin Nuclear Med 2004; 29: 81–85.
Zelefsky MJ, Scher HI, Forman JD, Linares LA, Curley T, Fuks Z . Palliative hemiskeletal irradiation for widespread metastatic prostate cancer: a comparison of single dose and fractionated regimens. Int J Radiat Oncol Biol Phys 1989; 17: 1281–1285.
Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol 2014; 15: 1397–1406.
Polkinghorn WR, Parker JS, Lee MX, Kass EM, Spratt DE, Iaquinta PJ et al. Androgen receptor signaling regulates DNA repair in prostate cancers. Cancer Discov 2013; 3: 1245–1253.
Spratt DE, Evans MJ, Davis BJ, Doran MG, Lee MX, Shah N et al. Androgen receptor upregulation mediates radioresistance after ionizing radiation. Cancer Res 2015; 75: 4688–4696.
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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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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DOI: https://doi.org/10.1038/pcan.2016.14
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