Editor’s Note: The 2024 European Society for Medical Oncology (ESMO) Annual Meeting was held from September 13 to 17 in Barcelona, Spain. Key research in the field of urologic oncology garnered much attention, particularly in the area of prostate cancer. The EORTC-GUCG 1333/PEACE-3 clinical trial (LBA1 - A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of Radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3) evaluated the efficacy of Radium-223 (Ra-223) combined with enzalutamide compared to enzalutamide alone in patients with bone metastatic castration-resistant prostate cancer (mCRPC) who were asymptomatic or had mild symptoms. The promising results sparked widespread interest. Urology Frontier invited the lead investigator of the study, Dr. Silke Gillessen from the Medical Oncology of the Università della Svizzera Italiana (USI) and Oncology Institute of Southern Switzerland (IOSI), to share her insights on this important research and discuss the potential treatment outlook for bone metastatic mCRPC patients.

01 Urology Frontier: Why is bone the most common site of metastasis in prostate cancer? Based on your clinical experience, what are the clinical presentations of prostate cancer bone metastasis?

Dr. Silke Gillessen: Indeed, many metastatic prostate cancer patients, especially those resistant to hormonal therapy, experience bone metastasis, with approximately 80% to 90% of them affected. While the exact reasons for this tendency are not fully understood, there are likely multiple factors contributing to prostate cancer’s proclivity to metastasize to bone. Clinically, patients with bone metastases from prostate cancer often present with bone pain, an increased risk of fractures, and in severe cases, spinal cord compression, which can manifest as neurological deficits, requiring urgent intervention. Bone metastasis is a major factor leading to a decline in the quality of life for prostate cancer patients.

02 Urology Frontier: Based on your clinical experience, what methods are available for detecting early bone metastasis?

Dr. Silke Gillessen: For a long time, we have relied on bone scans as an imaging technique. However, with the advent of PSMA (prostate-specific membrane antigen) PET scanning, we now have a more sensitive and accurate imaging technology that allows us to detect bone metastasis earlier. This has led to significant advancements in diagnosing bone metastasis.

03 Urology Frontier: At this year’s conference, you shared results from the EORTC-GUCG 1333/PEACE-3 study. How did enzalutamide alone compare to the combination of enzalutamide and Ra-223 in terms of efficacy?

Dr. Silke Gillessen: In patients who have already undergone ADT (androgen deprivation therapy) and whose disease has progressed to metastatic castration-resistant prostate cancer (mCRPC), the standard treatments typically include abiraterone or enzalutamide. Our aim was to explore whether adding Ra-223 to standard treatment could further improve outcomes. We aimed to see a 32% improvement in radiographic progression-free survival (rPFS), and the actual results showed a 31% increase in rPFS. Thus, we observed a statistically significant improvement in radiographic progression-free survival, which was our primary endpoint. Interestingly, we also saw a statistically significant improvement in overall survival in the log-rank test, which suggests that the combination of enzalutamide and Ra-223 has a positive effect on the prognosis of prostate cancer patients with bone metastasis.

Dr. Silke Gillessen Medical Oncologist, specializing in genitourinary cancers Professor Gillessen completed her training in Basel, St. Gallen, and at the Dana-Farber Cancer Institute in Boston. After returning to Switzerland, she established the Genitourinary Oncology Unit at the St. Gallen State Hospital and led the Clinical Research Unit in Oncology/Hematology. She has served two terms as Chair of the SAKK GU Group, Chair of the EORTC Genitourinary Cancer Group, and founded the Advanced Prostate Cancer Consensus Conference (APCCC). Since 2018, Professor Gillessen has been Chair of Genitourinary Cancer Systemic Therapy Research at the University of Manchester and Honorary Consultant at The Christie Hospital while continuing to work as a Consultant in Oncology/Hematology at the St. Gallen State Hospital in Switzerland. In January 2020, Professor Gillessen was appointed Director of Oncology at the University of Lugano (USI) and Professor of Oncology, as well as Director of the Oncology Institute of Southern Switzerland (IOSI) in Bellinzona.