Continued Focus on Bone Metastases to Improve Outcomes and Patient Care in Prostate Cancer
One area of continued development around bone metastatic disease involves the increasing utilization of PSMA PET scans in patients with localized prostate cancer. Guidelines suggest that these scans can be used for initial staging in patients with unfavorable intermediate, high, or very high risk localized disease.5 This approach to staging has led to the identification of bone metastases in at least 10% of patients who previously may have been missed by conventional bone and CT scan screening approaches in one landmark stud.6 This new lens on staging has caused stage migration on a large scale, and also raised the issue of high false positive lesions in ribs. It has also given us an opportunity to target oligometastatic sites with SBRT and investigate the use of PSMA targeted radioligand therapies in low volume metastatic states. In clinical practice, and in ongoing clinical trials, we are using this approach to see what was previously invisible to shift the trajectory of disease and investigate how to understand the new status of our patients best.
Further work on therapeutics has also occurred, with the PEACE-3 trial reporting out at ESMO 2024 as new evidence supporting the use of a bone targeted disease control strategy (Gillesson S, ESMO 2024). PEACE-3 is an international randomized phase 3 trial that included patients with metastatic castration-resistant prostate cancer (mCRPC) who were randomized to treatment with enzalutamide with or without radium-223. Patients had to have bone metastatic disease but were asymptomatic or mildly symptomatic from their disease, and they could have had soft tissue involvement but no visceral metastases. Approximately 30% had had prior treatment with docetaxel and approximately 2% had prior exposure to abiraterone acetate in the hormone sensitive setting. Importantly patients were mandated to use bone health agents (bisphosphonates or denosumab) per standard guidelines for mCRPC. In the analysis presented at ESMO, radiographic progression-free survival was prolonged with the combination of radium-223 plus enzalutamide versus enzalutamide alone (HR (95% CI) 0.69 (0.54-0.87)). There was also the suggestion of improved overall survival, which will be followed to ensure that this remains stable over time (HR (95% CI) 0.69 (0.52-0.90). Interestingly there was no difference in skeletal related events or time to pain progression between treatment arms, suggesting that the improvement in disease control was a cancer control effect on the prostate cancer cells themselves rather than simply a reduction in harmful bone related events or improved symptom management alone.
We have a lot to learn when it comes to bone metastases in prostate cancer, and an opportunity to improve the lives of our patients in the process. Whether we use bone health agents when appropriate to reduce complications, improve our ability to target metastases with radiation techniques or combine systemic treatment approaches to include addressing bone metastases, we are shifting the trajectories of cancer control and quality of life in the right direction. Ongoing efforts to improve the lives of our patients will include a focus on bone metastases, and updates in that area will be highlighted here so that we can learn together today, and make a difference in the clinic tomorrow.