Toxicity and Efficacy of Concurrent Androgen Deprivation Therapy, Pelvic Radiotherapy, and Radium-223 in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer

Abstract Purpose: Radium-223 is an alpha-emitting radionuclide associated with overall survival (OS) improvement in metastatic castration-resistant prostate cancer (mCRPC). External beam radiotherapy (EBRT) to prostate extends OS in men with metastatic hormone-sensitive prostate cancer (mHSPC) limited to less than 4 metastases. We hypothesized that combination radium-223 + pelvic EBRT could safely deliver maximal radiotherapy doses to primary and metastatic prostate cancer and may improve disease control. Patients and Methods: Thirty patients with de novo bone metastatic mHSPC who had commenced androgen deprivation therapy (ADT) and docetaxel were recruited to this single-arm, open-label, prospective clinical trial: Neo-adjuvant Androgen Deprivation Therapy, Pelvic Radiotherapy and RADium-223 (ADRRAD; for new presentation T1–4 N0–1 M1B adenocarcinoma of prostate). Study treatments were: ADT, 6 cycles of radium-223 q28 days, conventionally fractionated prostate radiotherapy (74 Gy) and simultaneous integrated boost to pelvic lymph nodes (60 Gy). Results: No grade 4/5 toxicity was observed. Three patients experienced grade 3 leukopenia, and 1 each experienced grade 3 neutropenia and thrombocytopenia; all were asymptomatic. One patient each experienced grade 3 dysuria and grade 3 urinary infection. No grade 3 gastrointestinal (GI) toxicity was observed. On treatment completion, there was a signal of efficacy; 24 (80%) patients had whole-body MRI evidence of tumor response or stability. Twenty-seven (90%) patients showed a reduction in alkaline phosphatase (ALP) compared with pretreatment levels. Median progression-free survival was 20.5 months. Conclusions: This is the first trial of combination ADT, radium-223, and EBRT to pelvis, post docetaxel. The combination was safe, with an efficacy signal. Multicenter randomized controlled trials (RCT) are warranted.