Endocrine Abstracts

Radium-223 was associated with high incidence of non-vertebral fractures in patients with castration-resistant prostate cancer (CRPC). The determinants of this effect are unknown and it is still unclear whether Radium-223 may induce skeletal fragility regardless of other therapies of CRPC. We aimed at evaluating the incidence and determinants of vertebral fractures (VFs), i.e. the hallmark of skeletal fragility, in CRCP patients undergoing Radium-223 therapy in the real-life clinical practice. We retrospectively reviewed 49 CRPC patients with symptomatic bone metastases treated with Radium-223 between July 2015 and May 2019. All patients underwent 11C-Choline PET/CT examination and VFs were assessed by the Genant’s method using lateral images of spine CT and excluding from the analysis the vertebral bodies affected by bone metastases. Before starting Radium-223, 24 patients (49%) had VFs significantly associated with duration of androgen-deprivation therapy (ADT) (odds ratio: 1.29, C.I. 95% 1.01–1.64; P = 0.04) and abiraterone acetate plus prednisone therapy (odds ratio 3.80, C.I. 95% 1.07–13.57; P = 0.04). Patients received median number of 4 radium-223 doses (range 2-6) and were followed-up for a median period of 11 months (range 2–44). Radium-223 therapy achieved bone pain relief in 81.3% of patients, average PSA values reduction of 248 ± 45%, progression free-survival and overall survival improvement, respectively in 41.7 % and 24.5% of patients. Forty-four patients were evaluated for incident VFs. During Radium-223 therapy, newVFs developedin 11 patients (25%) in relationship with pre-existing VFs (Hazard Ratio 6.89, C.I. 95% 1.17–40.59; P = 0.03) and change in serum alkaline phosphatase values (Hazard Ratio 0.97, C.I. 95% 0.95–0.99; P = 0.02), whereas the correlations with abiraterone plus prednisone therapy and duration of ADT were lost. Noteworthy, incident VFs did not correlate with the therapeutic outcomes of Radium-223. This observational study confirms that ADT may cause skeletal fragility especially when abiraterone is combined with prednisone. Interestingly, this study provides also aconvincing evidence that in real-life clinical practice, Radium-223 therapy may directly induce skeletal fragility with high risk of VFs independent of ADT and abiraterone plus prednisonetherapy. Therefore, skeletal health should be pro-actively evaluated in all patients with prostate cancer undergoing ADT and mainly in those candidate to Radium-223 therapy, in order to plan a therapeutic strategy for preventing fragility fractures in this clinical setting.