Prognostic factors that affect survival outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223.

Abstract

225 Background: Radium-223 (Ra-223) improved overall survival (OS) in men with mCRPC with predominantly bone metastases. We analyzed their survival outcomes to identify factors associated with prognosis for men treated with Ra-223. Methods: This was a retrospective study of men with mCRPC at Princess Margaret Cancer Centre treated with Ra-223. Demographics, disease characteristics, number of bone metastasis [ < 6, 6-20, > 20], laboratory results, number of Ra-223 doses, systemic treatment lines after radium-223, use of bone protecting agents (BPA) and survival outcomes were collected. OS and progression-free survival (PFS) were estimated by Kaplan-Meier (log-rank) analysis. Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) were used to evaluate patient and disease characteristics, number of Ra-223 doses and overall survival. Results: 114 men received Ra-223 between May 2015 and May 2018 with median age 75 years (range 53-93). Median radium doses was 5 (68 [59.6%] received > 4 doses, 46 [40.4%] received ≤4 doses). Median baseline ALP 113.5 U/L (31-1121), median baseline Hb 118 g/L (69-153), median baseline PSA 70.2 ug/L (0.15-5275), median LDH 242 UL (82-1426). 58% had 6-20 bone metastases and 28% had > 20 bone metastases. The median OS and PFS for men who received ≤4 doses vs > 4 doses was 4.56 vs 19.8 months (HR = 8.4; 95%CI: 4.861-14.62; p≤ 0.0001) and 2.9 vs 7.45 months (HR = 4.6; 95%CI: 2.837 to 7.537; p≤ 0.0001) respectively. The baseline median ALP was (154 vs 98; p = 0.03) for men who received ≤4 doses vs > 4 doses Ra-223. On UVA, ECOG 0-1 (HR = 0.33; p = 0.0003), baseline PSA < 70 ug/L (HR = 0.51; p = 0.0023), LDH < 250 U/L (HR 0.55; p = 0.0082), Hb > 120 g/L(HR 0.46; p = 0.0004), ALP < 150 U/l(HR 0.38; p ≤ 0.0001) and receipt of subsequent treatment after Ra-223 (HR = 0.33; p < 0.0001) were associated with improved OS. On MVA, receipt of subsequent treatment, administration > 4 cycles of Ra-223 and baseline ALP < 150 U/L were associated with improved OS. Conclusions: Men who receive > 4 cycles of Ra-223 have significantly better OS than those who receive ≤4 doses. Baseline ALP was independently associated with better OS and could be used to identify patients most likely to benefit from Ra-223.

Role of radium-223 discontinuation due to adverse events in castration-resistant prostate cancer patients. A retrospective monocentric analysis

“…No statistically significant correlation was found in our study between discontinuation of Ra-223 due to toxicity and number of metastases, PS, baseline PSA, ALP and NLR despite in previous studies these variables have been shown to correlate with OS. 13,17,20,22,23,25 Of course, the limited sample size of our series could imply a significant risk of false negative results in the analysis of single prognostic factors.…”

“…Several prospective and retrospective studies showed that a higher number of Ra-223 cycles is associated with survival advantage, demonstrating a significant decrease in median OS in patients who received 1 to 4 compared to patients treated with 5 or 6 Ra-223 administrations. 45,22 In the ALSYMPCA trial the median OS was 17.9 months in patients who received 5 or 6 Ra-223 administrations and 6.2 months in those treated with 1 to 4 administrations. 2 In the iEAP the median OS was 6.3 months in patients receiving less than 5 cycles compared to more than 16 months in those treated with 5 or 6 cycles.…”

“…Several prospective and retrospective studies showed that a higher number of Ra-223 cycles is associated with survival advantage, demonstrating a significant decrease in median OS in patients who received 1 to 4 compared to patients treated with 5 or 6 Ra-223 administrations. 45,22…”

“…In the international expanded access program (iEAP) 3b trial prognosis was better in patients with higher hemoglobin (Hb) levels, lower baseline ALP levels, good PS and no pain at baseline. 21 Al-Ezzi et al 22 demonstrated that patients who received more than 4 cycles of Ra-223 had significantly better OS and progression-free survival (PFS) than those who received ⩽4 doses (median 19.8 vs 4.56 months and 7.45 vs 2.9, respectively).…”

“…Al-Ezzi et al 22 demonstrated that patients who received more than 4 cycles of Ra-223 had significantly better OS and progression-free survival (PFS) than those who received ⩽4 doses (median 19.8 vs 4.56 months and 7.45 vs 2.9, respectively).…”