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



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.



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).



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.
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI, USA.
D E
DE
Spratt
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J R
JR
Osborne
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Z S
ZS
Zumsteg
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
K
K
Rebeiz
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J
J
Leeman
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
A
A
Rivera
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
M J
MJ
Morris
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
M J
MJ
Zelefsky
D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy; D003131:Combined Modality Therapy; D018450:Disease Progression; D015174:Epidural Neoplasms / Q000175:diagnosis / Q000556:secondary; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000401:mortality* / Q000532:radiotherapy*; D011883:Radium / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
D011883:Radium