Who is a bone-predominant patient to maximize clinical benefits of radium-223 dichloride?

Abstract

47 Background: Radium-223 dichloride (Ra-223) is used for patients with castration-resistant prostate cancer (CRPC) and bone metastasis (BM). However, some patients often have disease progression of non-BM during Ra-223 and may enable to receive no more other life-prolonging therapies. Thus, diagnostic uncertainty in bone-predominant CRPC yet needs to be determined. To maximize clinical benefits of Ra-223, we clarified how to identify patients with bone-predominant metastatic CRPC. Methods: This was a multi-center retrospective study. The 136 CRPC patients who received Ra-223 between 2012 and 2019 were reviewed. Patients without visceral metastasis and lymph node metastasis of more than 3 cm received Ra-223, 55kBq/kg, every 4 weeks for up to 6 cycles, and were required to continue androgen deprivation therapy alone. All patients were divided into 3 groups by the types of dynamic changes of BM compared to BM at diagnosis: i) only known lesions; ii) new progressive lesions; iii) de novo BM at CRPC. Time from initiation of Ra-223 to failure of subsequent treatment (time to FST), radiographic progression-free survival (rPFS) and overall survival (OS) were evaluated. Results: The median age was 76 years. Of all, 68% received all 6 planned cycles of Ra-223. Overall, PSA responses were observed in 26 (19%). During follow-up of 12 months, the median time of FST, rPFS and OS were 8.3, 10.6 and 16.4 months, respectively. The type of dynamic changes of BM (HR 3.65, p=0.004) and PSA doubling time (PSADT) just before Ra-223 (HR 4.35, p=0.006) were significantly associated with time to FST. The dynamic changes of BM combined with PSADT highlighted an optimal decision of Ra-223. Patients with only known lesions of BM had longer time to FST, better rPFS and OS regardless of PSADT. The same was true for patients with de novo or new progressive lesions of BM and a long PSADT. In contrast, patients with new progressive lesions of BM and PSADT< 3 months were presumably more likely to have the risk of FST and progression of visceral metastasis. Conclusions: Our findings suggest that the risk assessment with the type of dynamic changes of BM and PSADT could determine an ideal patient for Ra-223.