Clinical aspects of mCRPC management in patients treated with radium-223

Abstract

Bone is the most common site of metastasis in metastatic castration-resistant prostate cancer (mCRPC), which is associated with pain and skeletal events. Radium-223 dichloride (Xofigo) is an alphaemitting radioactive isotope that can specifically target bone lesions. Herein, we report the results of a retrospective analysis that documents our experience in the use of radium-223. Data from 63 patients (pts) with mCRPC who underwent radium-223 treatment from December 2015 to September 2017 were collected. Radium-223 (55 kBq/kg) was administered every 4 weeks for up to 6 cycles. The primary endpoint was OS. Radium-223 was administered as first line therapy in 11 pts, as second line in 19 pts, as third line in 16 pts and in successive lines in 17 pts; 42 pts out of 63 (67%) completed all six cycles. Within one month after the end of 6 cycles of radium-223, 15 pts out of 42 (35.7%) had achieved PR, 11 pts out of 42 (26.2%) had SD and 14 pts out of 42 (33.3%) had PD. Levels of pain decreased with progressive cycles of radium-223. After a minimum follow-up of 2 months and a maximum of 43 months, median OS was 15 months and median PFS was 8 months. The most frequent radium-223 related toxicity was low grade haematologic toxicity, predominantly G1-G2, that occurred halfway through treatment in about 75% of pts. The favourable results reported herein confirm that radium-223 can be considered well tolerated and effective in mCRPC, and is associated with significant decreases in pain. Prostate cancer is one of the most commonly diagnosed malignancies and a leading cause of cancer death in men 1. In 2012, there were over 1,000,000 newly diagnosed cases and >307,000 deaths from the disease worldwide 1. In Europe, in 2018, there were an estimated 450,000 new cases of prostate cancer 2 , and in the US, prostate cancer is the second leading cause of cancer deaths following those of the lung and bronchus 3. Even if several treatments are local, including radical prostatectomy, external radiotherapy and brachytherapy, which may allow eradication of disease in some patients (pts), roughly one-third of men will develop distant metastases 4. Even if long-term survival is relatively high, averaging 10 years in those with localised disease, in men with metastatic disease the 5-year survival rate decreases dramatically to approximately 30% 5. Such poor survival rates can be attributed in large part to resistance to treatment in which aggressive variants of prostate cancer arise following the accumulation of mutations in key tumour suppressor genes 6,7. Moreover, androgen depletion is known to induce genes involved in cancer progression and metastasis and the epithelial-to mesenchymal transition, which have implicated the bone-epithelial interaction as a key player in the progression of prostate cancer 8. Bone metastases dominate the clinical picture of advanced prostate cancer and are a major source of morbidity in metastatic disease 9. In pts with recurrence, bone is, in fact, the most common site of metastasis affecting more than 90% o...

Prognostic Value of 18F-Choline PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Radium-223

“…Of note, we found that all PET-responders presented a significant reduction in PSA/ ALP levels with respect to the baseline values, with a good correlation, although not statistically significant, between ∆TLA and ∆PSA. It has to be underlined that several reports indicate that PSA dosage might not represent a reliable approach for monitoring the response to treatment, since it may present a transitory increase after the first cycle of 223 Ra-therapy, in relation to the so-called "PSA flare" due to the release of PSA from tumor cell lysis [21]. The correlation between ∆TLA and ∆PSA found in our cohort might be explained by the inclusion criteria we applied for the enrollment, since only patients who had completed three cycles of 223 Ra-therapy were considered, thus minimizing the interference of "PSA flare" occurring in the first month of treatment.…”

Evolving Castration Resistance and Prostate Specific Membrane Antigen Expression: Implications for Patient Management

“…The standard treatment sequence involves taxane chemotherapeutics (docetaxel and cabazitaxel) and novel androgen deprivation therapy (abiraterone acetate, enzalutamide, apalutamide and darolutamide). Sipuleucel-T, an immune-modulatory cellular therapy, is only approved in the US, and treatment with Radium-223 for bone metastases has been moved to the third line of treatment due to a restriction of use by the EMA, although it is of benefit for particular patients [ 33 , 34 ]. First-line treatment of mCRPC is usually performed with abiraterone acetate and prednisone, enzalutamide, docetaxel or cabazitaxel.…”

Sequencing Life-Prolonging Agents in Castration-Resistant Prostate Cancer Patients: Comparison of Sequences With and Without 223Ra

“…A number of recently published real-world studies have described large series of patients treated with 223 Ra: they confirmed that the use of 223 Ra in therapeutic sequencing of mCRPC patients is active regardless of the treatment line, in which it was administered. [20][21][22][23] In particular, Rizzini et al 21 the changes occurring during its administration. The data concerning the changes in PSA and alkaline phosphatase levels during 223 Ra administration are very useful for assessing the clinical benefit of the treatment.…”