This trial showed that patients treated with radium-223 therapy versus placebo had significantly longer overall survival, along with other clinical benefits such as a reduction in the occurrence of skeletal-related events and enhanced quality of life. Because radium-223 therapy should be withheld in patients with substantial soft tissue involvement, patients were excluded in case of a history of visceral metastasis or malignant lymphadenopathy exceeding 3 cm in short-axis diameter. As patients in this study were enrolled between 2008 and 2011, soft tissue involvement was assessed through conventional imaging, i.e., abdominopelvic CT or chest x-ray.
Nowadays, however, conventional imaging is largely replaced by prostate-specific membrane antigen (PSMA) PET/CT in the staging and follow-up of metastatic prostate cancer. In addition, PSMA PET/CT is increasingly used as a screening method for systemic treatments such as PSMA radioligand therapy. This shift can be explained by the increased sensitivity and specificity that PSMA PET/CT offers as compared to conventional imaging. Nevertheless, the effect of this novel imaging modality on the outcomes of mCRPC therapies, which were originally proven effective through conventional imaging, remains unclear. Especially in radium-223 therapy, which should exclusively be administered in mCRPC patients with bone-only disease, modern imaging techniques can play a crucial role.
Therefore, our study aimed to analyze the impact of the imaging modality (PSMA PET/CT vs. CT) used in the selection of patients for radium-223 therapy on the outcomes.
We performed a secondary analysis of a prospective observational multicenter cohort study that included 122 mCRPC patients treated with radium-223 at 11 institutions throughout The Netherlands.2 Patients underwent either a baseline CT of the thorax and abdomen or a baseline PSMA PET/CT before initiation of radium-223. In addition, all patients underwent a baseline bone scintigraphy. Both biochemical response and overall survival were analyzed. We found a remarkably longer overall survival in the patients who received baseline PSMA PET/CT instead of baseline CT (19.9 vs. 12.4 months, p=0.038). This overall survival even exceeded the results from the ALSYMPCA trial. Furthermore, we noticed that in 40% of the patients in the baseline CT group, soft tissue involvement was newly detected on post-therapy CT, while none of the patients in the baseline PSMA group were diagnosed with soft tissue involvement during post-therapy imaging. Our exploratory analysis confirmed that the survival benefit favoring the baseline PSMA group was likely caused by the lack of soft tissue involvement in this group: no significant difference in overall survival was found between the baseline PSMA group and the baseline CT group without soft tissue involvement post-therapy.
In the future, prospective studies are needed, preferably double-blinded, to assess the influence of PSMA PET/CT on outcomes of radium-223 in mCRPC patients.
Written by: Dianne Bosch, MD & Maarten J. van der Doelen, MD, PhD, Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
References:
- Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–223.
- Bosch D, van der Velden KJM, Oving IM, et al. The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of 223Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients. J Nucl Med. 2024 Feb 29:jnumed.123.266654.