A Paradigm Shift in Cancer Staging - Seeing the Unseen with Circulating Tumor Cell Measurement

Abstract

The U.S. National Cancer Institute (NCI) defines the stage of cancer as the extent of cancer, with categories that reflect tumor size and tumor spread. Staging is meant to assist physicians to understand the seriousness of the cancer (for example chance of survival), and to select the best treatment plan to achieve optimal outcomes. By way of clinical experience, physicians understand that there are significant limitations of the current staging system. It is not unusual, for example, to see patients deemed to have a favorable prognosis or limited disease (by standard accepted staging), who develop early disease recurrence and distant spread. By examining the staging model more closely, it becomes clear that there is a serious omission: modern staging systems only factor in local invasion, micro and macroscopic lymphatic spread and macroscopic spread, while failing entirely to measure hematogenous spread. In recent years, new techniques have been developed that measure and quantify microscopic hematogenous spread, namely circulating tumor cell (CTC) identification and quantification. Hematogenous spread is a well-recognized phenomenon, and extensive data already exists which correlates CTC counts with disease recurrence and patient survival for many solid tumor types. Therefore a revision to the cancer staging system to include hematogenous spread is proposed. It is suggested that the new classification category "Hematogenous" (H) be adopted and measured through the routine use of CTC testing. This addition could result in a significant impact on patient survival for a wide range of cancer types.