An early study to assess response was done by Moertel and Hanley,² in which 16 experienced oncologists were asked to measure 12 simulated tumors, placed underneath foam, using their clinical methods, which entailed physical examination with a ruler or caliper. Although seemingly crude, this was an appropriate simulation of the clinical setting in which a physician will palpate a tumor and then estimate its size before and after administering the treatment. This paper suggested that a 50% reduction in the perpendicular diameters of the tumors done at approximately 2 months is an acceptable objective response rate. This 50% reduction in bidimensional measurement of a single lesion was adopted in the World Health Organization (WHO) guidelines in 1979. Miller³ and coworkers recommended that a partial response be identified if there is a 50% reduction in the bidimensional measure of tumor area or, if multiple tumors are present, the sum of the product of the diameters. This study also described unidimensional measurements for “measurable” disease, bone metastases, and criteria for “nonmeasurable” disease. Tumor volume estimates were based on conventional radiography techniques by measuring the two longest perpendicular diameters and their product. Although widely used, obvious shortcomings of the WHO guidelines were the clinical foundation of the criteria without accounting for the improvements in imaging to determine tumor volumes. Tumors are rarely round or symmetrical, thus making these measurements difficult to implement, particularly by using a ruler or calipers. The lack of distinction between a complete versus a partial response in 50% to 90% decrease in tumor volume was an obvious flaw.

The European Organization of Research and Treatment of Cancer (EORTC) and the National Cancer Institute (NCI) of the United States and Canada set up a study group (RECIST)⁴ to standardize assessment criteria in cancer treatment trials. The objective was to simplify and standardize the methods to assess tumor response by more precisely defining tumor targets with proposed guidelines on imaging methods. Revisions on complete response, partial response, stable disease, and progressive disease were done. Unidimensional measurements were established for lesions of 2 cm or larger for CT, MRI, plain film, and physical examination and 1 cm or larger for spiral CT scan. The sum of the unidimensional tumor measurements was used for evaluation of response, which may decrease the sources of error.

RECIST criteria were adopted by multiple investigators, cooperative groups, and industry and government entities in assessing the treatment outcomes. However, a number of questions and issues have arisen that have led to the development of revised RECIST 1.1 guidelines.

RECIST 1.1: The Current Standard

The major changes of RECIST 1.1 include the number of lesions required to assess tumor burden for response determination has been reduced to a maximum of five total (and two per organ, maximum). Assessments of pathologic lymph nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short-axis measurement should be included in the sum of lesions in calculation of tumor response. Nodes that shrink to less than 10 mm on the short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomized studies because the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5-mm absolute increase is now required as well to guard against overcalling progressive disease when the total sum is very small. Furthermore, guidance is offered on what constitutes “unequivocal progression” of nonmeasurable/nontarget disease, a source of confusion in the original RECIST guidelines. Finally, a section on detection of new lesions, including the interpretation of 2-[¹⁸F] fluoro-2-deoxy-D-glucose (FDG)–PET scan assessment, is included. Finally, the revised RECIST 1.1 includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions.⁵

The RECIST Working Group, in developing RECIST 1.1 concluded that, at present, there is not sufficient standardization or evidence to abandon unidimensional anatomic (vs. volumetric) assessment of tumor burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression.

Although these anatomic criteria have been evolving to affect better response criteria, the RECIST criteria and now, quite likely, the RECIST 1.1 criteria are or will be used in virtually every clinical trial of new solid tumor therapeutics, because response is essentially always measured. Regulatory agencies have accepted RECIST as the standard in response assessment for clinical trials in most countries. Familiarity with the implications of trials in which response is measured using the WHO, RECIST, and RECIST 1.1 criteria is essential because they are not identical and do not produce identical results. Table 5-1 presents RECIST 1.1 overall response criteria for both measurable and nonmeasurable lesions.

Table 5-1 RECIST 1.1 Target Lesions Response Criteria

Objective response	RECIST 1.1 target lesions^* change in sum of LDs, maximum of two per organ up to five total.
Complete response	Disappearance of all target lesions, confirmed at ≥ 4 wk. Reduction in short axis of target lymph nodes to < 10 mm.

Partial response Decrease in target LD sum ≥ 30%, confirmed at 4 wk. Progressive disease

Increase in target LD sum ≥20%.

Overall ≥ 5-mm increase in target LD sum.

New, malignant FDG uptake in the absence of other indications of progressive disease or an anatomically pre-existing lesion and confirmed on contemporaneous or follow-up CT.

Stable disease Does not meet other criteria.

CT, computed tomography; FDG, fluoro-2-deoxy-D-glucose; LD, lesion diameter; RECIST, Response Evaluation Criteria in Solid Tumors.

* Measurable lesion, unidimensional (LD only: size with conventional techniques ≥ 20 mm, with spiral CT ≥ 10 mm; nodes: target short axis ± 15 mm, nontarget 10- to 15-mm nodes, normal < 10 mm). Nonmeasurable: all other lesions, including small lesions; evaluable is not recommended.

From Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247.