223Ra-Dichloride in castration-resistant metastatic prostate cancer: improving outcomes and identifying predictors of survival in clinical practice

Abstract

Purpose: We first assessed whether the pattern of referrals to a nuclear medicine clinic improved as experience with ²²³Ra-dichloride increased, and whether referral patterns affected patient outcomes, and second assessed the value of bone scintigraphy, total alkaline phosphatase (tALP) and lymphadenopathy as prognostic factors in patients receiving ²²³Ra-dichloride.

Methods: A total of 57 patients eligible to receive ²²³Ra-dichloride over a 2-year period (March 2014 to March 2016) were retrospectively assessed and prospectively followed (median follow up 298 days). ²²³Ra-Dichloride was administered at 4-week intervals for a maximum of six injections. The numbers of patients in years 1 and 2 referred in relation to extent of bone disease (EOBD) category and overall survival (OS) were determined. The prognostic factors EOBD category, baseline tALP (tALP_BL), tALP response, greatest percentage reduction in tALP from baseline in any treatment cycle (ALP_max; among patients with elevated ALP_BL), and the presence of lymphadenopathy were assessed as predictors of OS.

Results: The proportion of patients with EOBD1 was higher in year 2 than in year 1 (29% and 4%, respectively), and in year 2 there was a lower rate of symptomatic skeleton-related events, a higher proportion of patients completing six cycles, and longer (albeit nonsignificant) OS (p = 0.55). There were significant differences in OS between EOBD4 patients and those in all other groups and between EOBD1 and EOBD3 patients (p < 0.05). OS was longer in patients with normal tALP_BL than in those with elevated tALP_BL (p = 0.01), in ALP responders than in nonresponders (p < 0.05), and in patients without lymphadenopathy than in those with lymphadenopathy (p = 0.29). OS was correlated with ALP_max (r² = 0.24).

Conclusion: A collaborative multidisciplinary referrals pathway, together with increased experience with ²²³Ra-dichloride, led to improved outcomes. In patients with elevated tALP_BL, tALP dynamics may be useful for monitoring response and predicting OS. Imaging and prognostic markers may therefore be of value for individualizing ²²³Ra-dichloride treatment and planning retreatment; however, further studies are required.

Keywords: 223Ra-Dichloride; Alkaline phosphatase; Bone metastases; Metastatic castration-resistant prostate cancer; Radium; Referral patterns.

Fig. 1

Pattern of referrals from uro-oncology to nuclear medicine in year 1 and year 2, in relation to the extent of bone disease (EOBD) category among the 57 included patients

Fig. 2

Overall survival in 26 patients in year 1 and 31 patients in year 2. Median survival times: 233 days in the total population, 227 days in year-1 patients, and 266 days in year-2 patients. Median follow-up times: 298 days in the total population, 234 days in year-1 patients, and 363 days in year-2 patients (p = 0.55, year 1 vs. year 2)

Fig. 3

Overall survival in relation to extent of bone disease (EOBD) category: 10 patients with EOBD1, 16 with EOBD2, 17 with EOBD3 and 14 with EOBD4. Median survival times: 437 days, 242 days, 250 days, and 116 days in patients with EOBD1, EOBD2, EOBD3 and EOBD4, respectively. Median follow-up times: 485 days, 359 days, 278 days, and 116 days, respectively. *p < 0.05 vs. EOBD4

Fig. 4

Overall survival in relation baseline alkaline phosphatase (ALP_BL) status (normal in 16 patients, elevated in 40; one patient did not have any baseline data). Median survival times: 401 days in patients with normal ALP_BL, and 222 days in those with elevated ALP_BL. Median follow-up times: 468 days in patients with normal ALP_BL, and 234 days in those with elevated ALP_BL. ,. *p = 0.01 vs. normal ALP_BL

Fig. 5

Overall survival in relation to alkaline phosphatase (ALP) response (≥30% vs. <30% reduction from baseline; 30 responders, 26 nonresponders). Median survival times: 363 days in ALP responders, and 115 days in ALP nonresponders. Median follow-up times: 411 days in ALP responders, and 170 days in ALP nonresponders. *p = 0.01 vs. ALP responders

Fig. 6

Overall survival in relation to alkaline phosphatase (ALP) response among patients with elevated total ALP at baseline (≥10% vs. <10% reduction from baseline; 34 responders, 6 nonresponders). Median survival times: 256 days in ALP responders, and 137 days in ALP nonresponders. Median follow-up times: 325 days in ALP responders, and 216 days in ALP nonresponders. *p = 0.03 vs. ALP responders

Fig. 7

Correlation between overall survival and greatest percentage reduction in total alkaline phosphatase (tALP) from baseline in any treatment cycle (ALP_max) among 40 patients with elevated tALP at baseline (r² = 0.24)

Fig. 8

Overall survival in relation to the presence lymph node disease (13 patients with lymph node disease, 30 patients without). Median survival times: 181 days in those with lymph node disease, and 325 days in those without lymphadenopathy at any stage. Median follow-up times: 221 days in those with lymph node disease, and 371 days in those without lymphadenopathy at any stage. p = 0.29 for presence vs. absence of lymph node disease