Novel nomogram developed for determining suitability of metastatic castration resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment – Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial

Abstract

Abstract Purpose: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration resistant prostate cancer (mCRPC) patients. Methods: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment at 14 hospitals between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. Results: Within median 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior new hormone therapy, never prior chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at one, two, and three years were 0.771, 0.818, and 0.771, respectively. A two-year survival calibration plot indicated consistent predicted and observed values without large discrepancy. Conclusion: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision making.