How does target lesion selection affect RECIST? A computer simulation study

RECIST is grounded on the assumption that target lesion selection is objective and representative of the change in total tumor burden during therapy. A computer simulation model was designed to challenge this assumption, focusing on a particular aspect of subjectivity: target lesion selection. Disagreement among readers, and between readers and total tumor burden was analyzed, as a function of the total number of lesions, affected organs, and lesion growth. Disagreement aggravates when the number of lesions increases, when lesions are concentrated on few organs, and when lesion growth borders the thresholds of progressive disease and partial response. An intrinsic methodological error is observed in the estimation of total tumor burden (TTB) via RECIST. In a metastatic setting, RECIST displays a non-linear, unpredictable behavior. Our results demonstrate that RECIST can deliver an accurate estimate of total tumor burden in localized disease, but fails in cases of distal metastases and multiple organ involvement. This is worsened by the "selection of the largest lesions", which introduce a bias that makes it hardly possible to perform an accurate estimate of the total tumor burden. Including more (if not all) lesions in the quantitative analysis of tumor burden is desirable.