Response evaluation criteria in solid tumors

Response evaluation criteria in solid tumors (RECIST) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. The criteria were published in February 2000 by an international collaboration including the European Organisation for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group. Today, the majority of clinical trials evaluating cancer treatments for objective response in solid tumors use RECIST. These criteria were developed and published in February 2000, and subsequently updated in 2009. The criteria are specifically not meant to determine whether patients have improved or not, as these are tumor centric, not patient centric criteria. This distinction must be made by both the treating physicians and the cancer patients themselves. Many oncologists in their daily clinical practice follow their patients' malignant disease by means of repeated imaging studies and make decisions about continuing therapy on the basis of both objective and symptomatic criteria. It is not intended that these RECIST guidelines play a role in that decision making, except if determined appropriate by the treating oncologist.

The RECIST specification establishes a minimum size for measurable lesions, limits the number of lesions to follow and standardizes unidimensional measures.

Only patients with measurable disease at baseline should be included in protocols where objective tumor response is the primary endpoint. Measurable disease – the presence of at least one measurable lesion. If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology. Measurable lesions – lesions that can be accurately measured in at least one dimension with longest diameter ≥20 mm using conventional techniques or ≥10 mm by spiral CT scan. Non measurable lesions – all other lesions, including small lesions (longest diameter <20 mm with conventional techniques or <10 mm with spiral CT scan), i. e., bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitis cutis/pulmonis, cystic lesions, and also abdominal masses that are not confirmed and followed by imaging techniques. All measurements should be taken and recorded in metric notation, using a ruler or calipers. All baseline evaluations should be performed as closely as possible to the beginning of treatment and never more than 4 weeks before the beginning of treatment. The same method of assessment and the same technique should be used to characterize each identified and reported lesion at baseline and during follow up. Clinical lesions will only be considered measurable when they are superficial (e. g., skin nodules and palpable lymph nodes). For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended.

CT and MRI are the best currently available and reproducible methods to measure target lesions selected for response assessment. Conventional CT and MRI should be performed with cuts of 10 mm or less in slice thickness contiguously. Spiral CT should be performed using a 5 mm contiguous reconstruction algorithm. This applies to tumors of the chest, abdomen and pelvis. Head and neck tumors and those of extremities usually require specific protocols. Lesions on chest X ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung. However, CT is preferable. When the primary endpoint of the study is objective response evaluation, ultrasound (US) should not be used to measure tumor lesions. It is, however, a possible alternative to clinical measurements of superficial palpable lymph nodes, subcutaneous lesions and thyroid nodules. US might also be useful to confirm the complete disappearance of superficial lesions usually assessed by clinical examination. The utilization of endoscopy and laparoscopy for objective tumor evaluation has not yet been fully and widely validated. Their uses in this specific context require sophisticated equipment and a high level of expertise that may only be available in some centers. Therefore, the utilization of such techniques for objective tumor response should be restricted to validation purposes in specialized centers. However, such techniques can be useful in confirming complete pathological response when biopsies are obtained. Tumor markers alone cannot be used to assess response. If markers are initially above the upper normal limit, they must normalize for a patient to be considered in complete clinical response when all lesions have disappeared. Cytology and histology can be used to differentiate between PR and CR in rare cases (e. g., after treatment to differentiate between residual benign lesions and residual malignant lesions in tumor types such as germ cell tumors).

All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, representative of all involved organs should be identified as target lesions and recorded and measured at baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements (either by imaging techniques or clinically). A sum of the longest diameter (LD) for all target lesions will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as reference by which to characterize the objective tumor response. All other lesions (or sites of disease) should be identified as non target lesions and should also be recorded at baseline. Measurements of these lesions are not required, but the presence or absence of each should be noted throughout follow up.

The RECIST criteria present problems for immunotherapies so around 2009 the immune related response criteria were developed and are used in some immunotherapy clinical trials.

The World Health Organization published the first tumour response criteria in 1981. However the specification documents were unclear which led to criteria adjustments and inconsistent conclusions. In the mid 1990s, an International Working Party was created to simplify and standardize response criteria; it then published RECIST in 2000. These new criteria have been widely adopted and embraced by the regulatory authorities. The mean response rate for new cancer drugs approved by the U. S. Food and Drug Administration, expressed as relative risk, ranges between 1.38x and 2.37x.