A5.3 Recurrence and progression

Topic

When a treated tumor regrows, it can do so in two distinct ways, depending on when the event occurs: recurrence is the increase in the number of tumor cells from a state of minimal residual disease to clinically detectable levels, following a period of response or stabilization; progression, by contrast, is the increase in tumor cell numbers while treatment is still active, without ever reaching that period of response or stabilization.

Although recurrence and progression occur at different times, they share the exact same underlying physics: in both cases, the tumor cell count had approached a state of control—where the number of cells tends toward zero—only to eventually break free from that state and revert to a state of escape, wherein the tumor regrows toward its maximum capacity.

What distinguishes recurrence from progression is not the physics, but the mechanism triggering the escape from the state of control: recurrence arises from minimal residual disease when residual tumor cells regain their net growth rate, whereas progression emerges from resistant clones within the tumor that were selected by the treatment itself while it was active.

The physics of recurrence is, specifically, the physics of tumor repopulation: the tumor regrows from the residual cells left behind as minimal residual disease, following the same growth kinetics—described by the Gompertz or logistic models—that govern the tumor at any other time. The time it takes for this repopulation to manifest as clinically detectable recurrence depends on two factors: the number of residual tumor cells remaining as minimal residual disease, and the speed of their net growth rate once it is restored. Therefore, for tumors with a slow net growth rate—such as low-grade prostate cancer or differentiated thyroid cancer—recurrence may take ten to twenty years to become detectable, whereas for tumors with a rapid net growth rate—such as pancreatic cancer, non-small cell lung cancer, or glioblastoma—recurrence occurs just weeks or months after treatment. In both cases, what determines when the tumor returns is not the treatment already administered, but the very physics of repopulation that governs tumor growth from the outset.

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