(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a prostate cancer poster session. Dr. Jonathan Tward presented the results of a phase 2 pilot study of Radium-223 and stereotactic body radiotherapy (SBRT) in untreated, hormone-naïve men with oligometastatic prostate cancer to the bone(s).
In this phase 2 pilot trial, Dr. Tward and colleagues hypothesized that treatment with Radium-223 and SBRT to ≤5 sites of bone metastases could safely delay the time to start of androgen deprivation therapy (ADT) and maintain quality of life (QoL). Eligible patients included those with previously treated (surgery, radiation, or both) prostate cancer in the non-metastatic state and who subsequently developed ≤5 bone-only oligometastases (i.e., metachronous oligometastases), confirmed on conventional bone scan and validated by a CT, MRI, or PET/CT. All patients were required to have testosterone levels ≥ 100 ng/dL. Exclusion criteria included receipt of LHRH therapies after the initial treatment or presence of N1 disease at diagnosis of the bone metastases. Patients received six cycles of Radium-223 and SBRT (30 Gy in five fractions between cycles 1 and 2). Bone scan was performed at baseline and every three months thereafter, with PSA performed monthly during the Radium-223 course and every three months thereafter, as well.
The primary study endpoint was freedom from ADT use at 15 months, with therapeutic effectiveness defined as ≥20% of patients meeting this endpoint. Discontinuation of study therapy occurred if:
- PSA rose by >10%, if baseline PSA >20ng/ml
- PSA>20, if baseline PSA <20 ng/ml
- Radiographic progression or a skeletal-related event (SRE)
Of note, the T0 (i.e., start of follow-up) was defined as the date of receipt of Radium-223 Cycle 1. Patients were followed for two years. Clinically significant changes in patient-reported outcome (PRO) measures were defined as those changes >1/2 standard deviation from the mean baseline value and were censored after the time of ADT use. Statistical comparisons were performed using the Wilcoxon rank sum and Pearson’s Chi-square tests, as well as univariable Cox regression analyses. p<0.05 denoted statistical significance.
The study cohort included 20 patients. The median number of Radium-223 cycles administered was six. Six patients received <6 cycles (range: 2 to 5) due to disease progression.
Freedom from ADT use at 15 and 24 months was 50% and 40%, respectively (p<0.001). The median time to ADT was 15 months.
PSA 50 and 90 declines were observed in 11 (55%) and five (25%) patients, respectively. Two patients had undetectable (PSA<0.01) at two years. On univariable analysis, the investigators failed to identify any variables significantly predictive of the primary outcome of freedom from ADT at 15 months.
There were no significant changes from baseline in any PRO QoL domain (physical functioning, anxiety, depression, fatigue, satisfaction with participation in social roles, sleep disturbance, and pain interference).
Grade 3 SREs were observed in two patients (bone fracture, pain). Grade ≥2 events attributed as possible or likely due to Radium-223 were seen in four patients and included bone pain, fatigue, fracture, and a decreased WBC count. Grade ≥2 events attributed as possible or likely due to radiotherapy were seen in two patients, including fatigue and other pain.
Dr. Tward concluded that in this prospective pilot study, the first-line use of Radium-223 and SBRT to conventionally imaged oligometastatic bone metastases in hormone-naïve men resulted in a significant delay in ADT use, compared to historical controls. This combinatory therapy approach is well tolerated, maintains QoL, and may result in undetectable PSA.
Presented by: Jonathan David Tward, MD, PhD, FASTRO, Professor, Department of Radiation Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024