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.

在转移性癌症患者中证明的治疗的临床益处导致乐观且可以理解的合乎逻辑的信念，即相同的治疗可能对那些在去除原发性癌症后导致疾病复发的明显静止的恶性细胞有效。因此，一个简单的范式指导了实体瘤辅助全身治疗的发展：将发现在转移性疾病中有效的全身治疗方案施用于疾病复发高风险的患者亚群。事件延迟（即，在接受辅助治疗的患者中，在选定的时间点复发或死亡减少）表明辅助治疗带来的益处。使用这种经典范例的成功很多，但大多数情况下，它们的效果并不明显，有时需要进行荟萃分析以提取令人信服的治疗效果证据。不幸的是，虽然可以理解，但由于现有技术的限制，这一过程的表面上的简单性和成功的希望已经削弱了对两种相关但不同的现象——生物学——的复杂性可能存在的关键差异进行更深入调查的动力。已建立和可见生长的转移性肿瘤，以及转变中明显静止的恶性细胞的生物学。