Clinical indicators for predicting prognosis after radium-223 administration in castration-resistant prostate cancer wit
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ORIGINAL ARTICLE
Clinical indicators for predicting prognosis after radium‑223 administration in castration‑resistant prostate cancer with bone metastases Yoshiyuki Yamamoto1 · Yohei Okuda1 · Tomohiro Kanaki1 · Ryo Tanaka1 · Akira Nagahara1 · Yasutomo Nakai1 · Masashi Nakayama1 · Ken‑ichi Kakimoto1 · Kazuo Nishimura1 Received: 6 June 2020 / Accepted: 19 August 2020 © Japan Society of Clinical Oncology 2020
Abstract Background Radium-223 (Ra-223) is a targeted alpha therapy that has been shown to prolong overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, prognosis after Ra-223 administration varies among patients. The aim of the present study was to assess risk factors associated with the poor prognosis of patients treated with Ra-223. Methods We retrospectively reviewed patients’ records of treatment with Ra-223 between October 2016 and December 2019. All patients had mCRPC, bone metastasis, and no known visceral metastases, and received up to six cycles of Ra-223 (55 kBq/kg). Prognostic factors for OS were analyzed by Cox proportional hazards model and log-rank test. Results We identified 42 patients who received at least one cycle of Ra-223 (median six cycles, range 1–6). Approximately two-thirds of patients had received at least two lines of therapy for mCRPC. The median age was 74 years, and the median follow-up duration was 13.6 months. The median OS time was 16.6 months. On multivariate analysis, PSA doubling time (PSADT) (0–3 months) at baseline, number of bone metastases (≥ 20), and treatment line of Ra-223 (4th–5th line) remained significantly correlated with the poor OS (HR 4.354, P = 0.003; HR 2.855, P = 0.020; and HR 4.871, P = 0.001, respectively). Conclusions Our study demonstrated that a shorter PSADT, a heavier volume of bone metastases, and a later treatment line before Ra-223 are poor prognostic factors for mCRPC patients. These newly discovered risk factors may help select patients who potentially have long-term OS after Ra-223 treatment. Keywords Castration-resistant prostate cancer · Number of bone metastases · Overall survival · PSA doubling time · Radium-223 Abbreviations AE Adverse event ALP Alkaline phosphatase HR Hazard ratio mCRPC Metastatic castration-resistant prostate cancer LDH Lactate dehydrogenase OS Overall survival OR Odds ratio PS Performance status PSADT PSA doubling time Ra-223 Radium-223 * Kazuo Nishimura [email protected] 1
Department of Urology, Osaka International Cancer Institute, 3‑1‑69 Otemae, Chuo‑ku, Osaka 541‑8567, Japan
Introduction Metastatic prostate cancer has a poor prognosis of 42 months for overall survival (OS) [1] owing to the development of metastatic castration-resistant prostate cancer (mCRPC). Since 2010, the number of life-prolonging treatments for mCRPC has increased from one (docetaxel) to six, dramatically expanding treatment options and creating the potential to combine therapies for mCRPC. These options are docetaxel [2], sipuleucel-T [3], cabazit
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