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

PurposeWe first assessed whether the pattern of referrals to a nuclear medicine clinic improved as experience with Ra-223-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 Ra-223-dichloride.MethodsA total of 57 patients eligible to receive Ra-223-dichloride over a 2-year period (March 2014 to March 2016) were retrospectively assessed and prospectively followed (median follow up 298days). Ra-223-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.ResultsThe 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) (r(2)=0.24).ConclusionA collaborative multidisciplinary referrals pathway, together with increased experience with Ra-223-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 Ra-223-dichloride treatment and planning retreatment; however, further studies are required.