The overall survival (OS) data from the EMBARK trial, showing a significant benefit for intermittent therapy escalation in high-risk prostate cancer, was unprecedented. The Kaplan-Meier curves prompted a spontaneous applause from the audience, highlighting the data's profound impact and the dramatic hazard ratio for OS, not seen in this setting for a long time.
The PRESTO trial evaluated adding apalutamide (APA) and abiraterone (Abby) to a standard LHRH analog. The triplet combination arm demonstrated increased toxicity without any additional efficacy gains compared to the doublet arm (LHRH + APA). This finding reinforces that more intensive combination therapy is not always better and can be detrimental in this setting.
The patient population in pivotal trials like EMBARK, defined as non-metastatic by conventional imaging, is being re-evaluated. A UCLA study showed that over 80% of a similar patient group would have been positive on a PSMA PET scan, suggesting the "M0" classification is largely an artifact of older imaging technology and that these patients likely have micrometastatic disease.
For patients with conventionally negative imaging but positive PSMA PET scans (oligometastatic disease), continuous intensified therapy may be overtreatment. A new paradigm involves metastasis-directed therapy followed by a short course of escalated treatment, then stopping to observe. This "time-limited" approach balances efficacy with reducing long-term treatment burden.