Mathematical modeling reveals that metastatic prostate cancer can be managed by deliberately guiding tumor evolution rather than attempting maximum cell kill. The approach leverages Darwinian selection principles, using adaptive dosing schedules and exploiting collateral sensitivities where resistance to one treatment creates vulnerability to another. Radiopharmaceutical agents combined with immunotherapy provide particularly effective tools for implementing these evolution-informed strategies across disseminated disease sites. This paradigm shift represents a fundamental departure from traditional maximum tolerated dose protocols that inadvertently accelerate resistance development. The evolutionary approach mirrors successful applications in other complex biological systems, from antibiotic stewardship to pest management, where working with natural selection proves more durable than fighting against it. For advanced prostate cancer patients, this could mean transforming an inevitably fatal diagnosis into a manageable chronic condition. The strategy requires sophisticated computational models to predict evolutionary trajectories and real-time treatment adjustments, making it technically demanding but potentially transformative. Early clinical applications suggest meaningful extensions in progression-free survival, though longer follow-up is needed to demonstrate overall survival benefits.