A5.2 Minimal residual disease

Topic

Minimal residual disease refers to the persistence of tumor cells within the body following a treatment that appears successful at first glance, as both imaging and microscopic tissue examination indicate a complete response.

Minimal residual disease represents the state existing between that clinically observed complete response and the patient's actual biological cure: the patient appears cured, yet residual tumor cells—ranging from one hundred to one hundred million—remain in the body, a quantity too small to be detected by standard methods.

These residual tumor cells can follow one of two paths: the patient's immune system may keep them in a state of dormancy—where they neither grow nor disappear entirely—or, over time, the cells may begin to multiply again and repopulate the tumor, a process known as recurrence.

Detecting these residual tumor cells is, in itself, a physics challenge: conventional imaging—such as computed tomography (CT) or magnetic resonance imaging (MRI)—can only detect a tumor once it contains between one hundred million and one billion cells, roughly equivalent to a volume of one cubic centimeter. Below this cell count, the tumor becomes invisible to conventional imaging, even though residual tumor cells remain present.

Below the detection threshold of conventional imaging, only a few ultrasensitive molecular techniques can identify residual tumor cells: detecting tumor genetic material circulating freely in the patient's blood; identifying individual tumor cells in the blood or bone marrow using specialized techniques primarily employed for blood disorders; or using positron emission tomography (PET) with highly sensitive tracers. The difference between whether or not these ultrasensitive molecular techniques detect residual tumor cells—a state known as minimal residual disease being positive or negative—can represent several orders of magnitude in the patient's tumor cell count: ranging from one hundred million cells (the limit of detection for conventional imaging) to fewer than one hundred cells (the limit for the most sensitive molecular techniques). This vast difference is precisely what renders minimal residual disease invisible to conventional imaging, yet detectable only through the submicroscopic detection physics underpinning these molecular techniques.

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