When progressive disease does not mean treatment failure: reconsidering the criteria for progression

Abstract

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of "objective progression" is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology.

Figure 1.

Response and progression as distinct events in solid tumor oncology care and research. Because response and progression play two very different roles, the two may be better conceptualized as distinct events rather than as the two ends of a single spectrum, and each can be studied and critiqued separately.