Conventional radiotherapy for high-risk prostate cancer (PCa) is built around maximally tolerated dose (MTD) escalation aimed at total ablation of the tumor. In aggressive disease (Gleason 8–10, ISUP grade 4–5), this approach systematically triggers competitive release: by eliminating treatment-sensitive clones, MTD removes the competitive pressure that previously constrained the expansion of resistant subpopulations. We propose an alternative strategy — subablative fragmentation of tumor coordination nodes — whose objective is not the destruction of total tumor mass, but the disruption of the focus's internal signaling connectivity. A tumor stripped of coordination between its subpopulations breaks down into isolated, mutually competing groups, becomes more accessible to immune surveillance, and recovers sensitivity to systemic therapy (androgen deprivation therapy, ADT). The strategy draws on the precedent of Gatenby's adaptive therapy program (Phase II, metastatic castrate-resistant PCa) and proposes a concrete protocol for transitioning from ablation to evolutionary management of the disease.
Anatoliy Kremenchutskiy (Fri,) studied this question.