Progression in oncology trials is most often defined by Response Evaluation Criteria in Solid Tumors (RECIST), a framework that standardizes response assessment but oversimplifies the biological complexity of treatment failure. Efforts such as immune RECIST (iRECIST) have adapted these criteria for atypical response patterns seen with immunotherapy, yet the broader temporal and spatial dimensions of progression remain underexplored. Emerging evidence from lung and prostate cancer suggests that not all progression is equivalent: the velocity of disease spread, the tropism or organ site of failure, and the burden of progression each carry prognostic and therapeutic significance. Faster or organ-specific progression can reflect distinct resistance mechanisms, microenvironments, and implications for local versus systemic therapy. Integrating these dimensions into clinical trial endpoints-alongside established measures such as time to progression, time to next systemic therapy, or post-treatment failure-free survival-could improve interpretability and relevance to clinical decision-making. Prospective, standardized collection of lesion-level and temporal data is essential to validate these approaches and mitigate biases inherent to retrospective analyses. Recognizing that not all failure is the same, future studies should systematically characterize and report the pattern, velocity, and burden of progression to refine therapeutic sequencing and align trial endpoints with the biological realities of metastatic disease.
Venkateswaran et al. (Sun,) studied this question.