Top Line: When we think about any therapy in oncology, the idea is to administer maximally tolerated treatment and eliminate as many cancer cells as possible. However, there is often a subset of tumor cells that will be resistant to therapy and ultimately lead to resistant disease.
The Study: This paper describes a concept called adaptive therapy (though it isn’t really the kind of adaptive therapy that phrase usually refers to). It uses an evolutionary rationale to hypothesize that preserving some therapy-sensitive cells with on/off therapy may competitively suppress the takeover of therapy-resistant cells. In a previous pilot study of 13 patients with mCRPC, “adaptive therapy” consisted of abiraterone until PSA dropped by 50% and then no treatment until the PSA reached the original baseline again. The challenge is identifying the right population of patients in which to test this approach. The analyzed the small pilot population with another 40 patients with nonmetastatic castration sensitive prostate cancer treated with intermittent ADT, which is very different from their concept of adaptive therapy but still offered on-off therapy cycles. They sought to use PSA kinetics from the first treatment cycle to predict who would actually benefit from the adaptive approach. Over-simplified, their mathematical model used the kinetics of the PSA drop (how hard therapy hits the sensitive cells), the PSA rebound (how much competition for regrowth), and the asymmetry between these (the rate of cell turnover) to derive an adaptive therapy score. The adaptive therapy score predicted time to progression in the CSPC cohort and correlated strongly with TTP in mCRPC, though not significant. Conventional PSA metrics (nadir, time to nadir, doubling time) showed no association with TTP or OS.
TBL: While this is largely investigational and based on very small numbers, it is an interesting and different way to think about tumor response to therapy. Within this model, tumors near their carrying capacity with high cell turnover (where competition can suppress resistant clone expansion) are the ones predicted to benefit from adaptive scheduling. | Gallagher, JAMA Oncol 2026
The Study: This paper describes a concept called adaptive therapy (though it isn’t really the kind of adaptive therapy that phrase usually refers to). It uses an evolutionary rationale to hypothesize that preserving some therapy-sensitive cells with on/off therapy may competitively suppress the takeover of therapy-resistant cells. In a previous pilot study of 13 patients with mCRPC, “adaptive therapy” consisted of abiraterone until PSA dropped by 50% and then no treatment until the PSA reached the original baseline again. The challenge is identifying the right population of patients in which to test this approach. The analyzed the small pilot population with another 40 patients with nonmetastatic castration sensitive prostate cancer treated with intermittent ADT, which is very different from their concept of adaptive therapy but still offered on-off therapy cycles. They sought to use PSA kinetics from the first treatment cycle to predict who would actually benefit from the adaptive approach. Over-simplified, their mathematical model used the kinetics of the PSA drop (how hard therapy hits the sensitive cells), the PSA rebound (how much competition for regrowth), and the asymmetry between these (the rate of cell turnover) to derive an adaptive therapy score. The adaptive therapy score predicted time to progression in the CSPC cohort and correlated strongly with TTP in mCRPC, though not significant. Conventional PSA metrics (nadir, time to nadir, doubling time) showed no association with TTP or OS.
TBL: While this is largely investigational and based on very small numbers, it is an interesting and different way to think about tumor response to therapy. Within this model, tumors near their carrying capacity with high cell turnover (where competition can suppress resistant clone expansion) are the ones predicted to benefit from adaptive scheduling. | Gallagher, JAMA Oncol 2026