Title : Role of radium 223 dichloride in treatment of symptomatic skeletal metastases in castration resistant prostate cancer (mCRPC)
Radium-223 dichloride (Ra-223) is indicated in patients with castration resistant prostate cancer with symptomatic bone metastasis but without any known visceral metastatic disease.Radium-223 dichloride primarily prolongs survival, improves quality of life (proven by ECOG score), improves pain relief and reduces skeletal events. Castration is achieved by androgen deprivation therapy (ADT) and confirmed with target serum testosterone level below 20 ng/dL. Progression of disease after achieving castration is diagnosed by serial rise in PSA, new symptoms and metastatic foci confirmed by appropriate imaging study. Careful selection of patients before start of therapy is made by attention to strict hematologic inclusion criteria. Although 75% of patients had an increase in PSA levels during therapy with Ra-223, increasing the drug dose and addition of anti-androgen therapy helped reduce the PSA. Alkaline phosphatase is (ALP) still is the best biochemical marker for response to therapy with baseline being >200IU/L. On an average 10% weight loss is seen during therapy, more so after the 3rd dose and which in turn is seen to negatively impact the Ra-223 dose which is body weight based.Diarrhea occurs in half the patients with prior pelvic EBRT, which usually responds to Bismuth subsalicylate prophylaxis. Ra-223 may be initiated after cytotoxic therapy as soon as the marrow recovery begins. Tumor destruction is directly proportional the alpha particle concentration which reduces exponentially as tumor mass decreases over course of therapy. Factor to consider during therapy are local infiltration, incontinence, post therapy radiation safety precautions, the half-life of 11.4 days and osteogenic agents like bisphosphonates. Future research needs focusing on concurrent Ra-223 & cytotoxic chemotherapy, treatment in non-castrated or with visceral metastases and extending therapy to other skeletal metastases.