Optimization of Radium-223 Treatment of Castration-resistant Prostate Cancer Based on the Burden of Skeletal Metastasis and Clinical Parameters

Patient selection methods are suboptimal for determining who will benefit most from Ra-223 treatment for prostate cancer that has metastasized to bone. This article characterizes bone scintigraphy as a potentially useful and important biomarker for patient selection and prognosis. Background Radium-223 dichloride (Ra-223) is now frequently used to treat prostate cancer that has metastasized to bone, although patient selection continues to be suboptimal for determining who will benefit most from this novel treatment modality. Materials and Methods Seventy-nine patients with metastatic castration-resistant prostate cancer (mCRPC) were treated with Ra-223 from 2012 to 2016. The burden of skeletal metastasis was determined for each using the Bone Scan Index (BSI) as a ratio of diseased to normal bone. Clinical, laboratory, and survival data were collected and examined for associations with BSI, and treatment tolerability was assessed. Results Chemotherapy-naive patients were significantly more likely to complete the full course of treatment. Median follow-up was 31 months (range 0.7-38.8 months) and median overall survival was 15.4 months (range 9.5-20.6 months). Overall survival was significantly associated with findings on bone scans (P < .05). Patients with higher BSI tended toward poorer outcomes. Nearly half the patients with low baseline BSI survived 3 years or more following Ra-223 treatment. By contrast, only 20% of the patients with high baseline BSI lived for 1 year, and none lived for an additional 3. Baseline BSI was significantly associated with decreased hemoglobin, higher serum PSA and alkaline phosphatase levels, and treatment-associated reductions in platelet and absolute neutrophil counts. Conclusion Our results suggest better outcomes to Ra-223 therapy for patients who are chemotherapy-naive and who undergo treatment earlier in the course of their disease as reflected by low BSI and concordant laboratory parameters.

Automated summary

This study identifies bone scintigraphy as a potentially important biomarker for selecting prostate cancer patients with bone metastasis who will benefit most from Ra-223 treatment. Patients with lower baseline Bone Scan Index (BSI) levels are more likely to have better outcomes following treatment, while those with higher BSI levels have poorer survival rates.