Clinical benefit of a treatment demonstrated in patients with metastatic cancer leads to an optimistic and, understandably, logical belief that the same treatment is likely to be active against those apparently quiescent malignant cells that lead to disease recurrences after removal of the primary cancer. Thus, a simple paradigm has directed the development of adjuvant systemic therapy of solid tumors: administration of the systemic treatment regimen found to be active in the metastatic disease to a subset of patients at high risk of disease recurrence. Delaying of events (ie, fewer relapses or fewer deaths at a selected time point, in those receiving the adjuvant treatment) indicates the benefit derived from the adjuvant treatment. Successes using this classic paradigm have been many, but most often they are modest in effect and at times have required meta-analyses to extract a convincing evidence of treatment efficacy. Unfortunately, though quite understandably, the apparent simplicity and a promise of success of the process, confounded by the limits of available technology, has curtailed motivation to a deeper inquiry into the likely critical differences in the complexities of 2 related but distinct phenomena—the biology of established and visible growing metastatic tumors, and the biology of the apparently quiescent malignant cells in transition.
Mann B, Zwiebel J. Planning Adjuvant Trials When Regimens Effective for Patients With Advanced Disease Don’t Work in the Adjuvant Setting—Paradigms Lost. JAMA Oncol. 2017;3(9):1178–1179. doi:10.1001/jamaoncol.2017.0066
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