Several important trials were published in 2022 in the field of advanced prostate cancer, but the most important, to me, were the STAMPEDE group's data on very high–risk prostate cancer patients with no distant metastatic disease on conventional imaging. This study was published in The Lancet in 2022.1
Bottom line: These phase III trials were practice-changing for those men diagnosed with very high–risk nonmetastatic castration-sensitive prostate cancer (or pelvic node–positive disease), and androgen deprivation therapy (ADT) + abiraterone/prednisolone + radiation provided more benefit than ADT + radiation in this setting.
The details of this important trial are somewhat complex. To be eligible for the study, patients with “high-risk” nonmetastatic hormone-sensitive disease had to have two of the following three characteristics: T3 or T4 clinical stage, Gleason score 8 to 10, and PSA greater than 40 ng/mL; or they had to have pelvic nodal disease. This article from The Lancet is one publication that covers two randomized phase III trials combined, and, overall, the publication reports on a total of 1974 randomized patients. The first trial utilized systemic therapy using ADT versus ADT + abiraterone/prednisone, and the second trial used ADT versus ADT + abiraterone/prednisolone + enzalutamide. In the end, there was no added value with the addition of enzalutamide to the systemic therapy, and the enzalutamide-treated patients were combined in the analysis of patients treated with ADT + abiraterone/prednisolone.
All patients were eligible for radiation, and approximately 85% of the patients received external beam radiation to the prostate. In the control arm, ADT alone was administered for 3 years, whereas, in the experimental arms, 2 years of hormonal therapy was utilized. Local radiotherapy was mandated for those men with node-negative disease and encouraged for those with node-positive disease. A total of 39% of the patients had node-positive disease. Radiation was planned to be given to approximately 85% of the patients. The median age was 68 years, and the median PSA level was 34 ng/mL.
The primary endpoint was metastasis-free survival (MFS). The secondary endpoints included overall survival (OS) and prostate cancer–specific survival (PCSS). The trial was unequivocally positive, showing improvements in the ADT + abiraterone/prednisolone arm. The MFS hazard ratio (HR) was 0.53. The OS HR was 0.60, and the PCSS HR was 0.49. All of these findings were highly statistically significant. The MFS at 6 years was 69% in the control arm versus 82% in the abiraterone group. The therapy was well-tolerated as a whole.
The trial was not perfect. No doubt many of these patients had metastatic disease that would have been detected by PSMA PET scans, but no PET scans were performed. That said, the overall findings were striking, and, in patients with very high–risk "localized" disease or those with pelvic metastatic disease, the trial strongly favored ADT + abiraterone/prednisolone + external beam radiation and that should be the current standard of care for those patients who fulfill the STAMPEDE entry criteria.