iRECIST is a standardized assessment system for tumor response under immunotherapy in trials involving solid tumors. It builds on RECIST 1.1, but adds the categories of immune-confirmed and immune-unconfirmed progression. This accounts for the fact that an initial increase in tumor burden or new lesions under immunotherapy can later transition into a response.
Starting Point: RECIST 1.1
RECIST 1.1 classifies findings based on target lesions, non-target lesions, and new lesions. A new lesion establishes progression there if it is unequivocally pathological. The system thereby assigns each assessment to an objective response, stable disease, or progression, and provides the basis for comparable capture of tumor burden across many oncology trials.
With immunotherapies, however, patterns can emerge that are difficult to capture with this immediate classification. The initial appearance of apparent worsening can be related to immune cell infiltration or a delayed antitumor effect. iRECIST was developed as a consensus framework to capture such observations without fully abandoning the proven RECIST structure.
Categories and Confirmation of Progression
For objective responses, iRECIST uses the categories iCR, iPR, and iSD. If a finding occurs that would qualify as progression under RECIST 1.1, iUPD—immune unconfirmed progression—is documented first. This may include an increase in tumor burden or new lesions. An iUPD does not necessarily conclude the assessment definitively.
The following imaging determines whether the progression is confirmed. If tumor burden continues to increase or new lesions show further growth, iCPD, immune-confirmed progression, is recorded. If the findings remain stable or show regression, the classification can be adjusted under the iRECIST rules. The pre-planned assessment timepoints are particularly important for this logic.
Distinction from RECIST 1.1
The key difference lies in how the first progression is handled. In RECIST 1.1, an unequivocally new lesion leads directly to progression. iRECIST initially records the same finding as iUPD and requires confirmation, provided further assessment is feasible under the protocol and clinically justifiable. New lesions are therefore not ignored, but are placed differently within the temporal decision-making logic.
iRECIST is neither a general replacement for RECIST 1.1 nor justification for continuing an effective therapy beyond clinically appropriate limits. The guideline serves data collection in trials; decisions regarding continuation of treatment additionally take into account the patient’s clinical condition and the requirements of the protocol. The categories do not render an immunotherapy effective per se.
For comparability, it is important that iRECIST does not replace the original measurements with a free-form, immunotherapy-specific impression. Target lesions continue to be systematically measured, non-target lesions assessed, and new lesions documented. The “i” prefixes indicate how the course is classified for immunotherapy evaluation purposes. Datasets should therefore record both the observation—such as a new lesion or change in size—and the resulting category in a traceable manner. The category alone, without the underlying examination findings, does not allow for a robust central review. iRECIST also makes clear that its guidelines were primarily developed for data collection in clinical trials and are not readily applicable to guiding routine care.
Documentation of an iUPD can also affect the analysis of best response and progression-related endpoints. For this reason, an assessment must not be changed retroactively without a traceable finding. Central review and investigator site assessment require the same definitional basis and the same imaging dataset. If RECIST 1.1 is additionally reported, it must remain transparent whether the results were collected in parallel or merely derived afterward. This prevents categories with different progression logic from being conflated into a single metric.
Relevance for clinical trials
An iRECIST protocol must clearly specify the population and imaging examinations to which the criteria apply. Imaging windows, handling of new lesions, documentation of an iUPD, and requirements for the confirmatory assessment must be consistent across the eCRF, Imaging Charter, and statistical analysis plan. The question of whether tumor assessments continue to be collected after an iUPD also requires a clear rule.
Full-service CROs such as Mediconomics support the operationalization of iRECIST within the protocol and imaging documentation. They coordinate sites, central image review, data management, and biostatistics, ensuring that iUPD, iCPD, assessment timepoints, and deviations are captured as distinguishable data points and are not mixed with RECIST 1.1 results in clinical reports.
Frequently Asked Questions (FAQ)
Does iUPD mean the trial has no progression finding?
No. iUPD records progression following the first notable finding. The term indicates that the progression has not yet been confirmed within the iRECIST framework.
When does iCPD occur?
iCPD is documented at a subsequent assessment when the criteria for confirming a previously identified iUPD are met. The evaluation follows the predetermined assessment schedule.
Can a new lesion be disregarded under iRECIST?
No. It is recorded and can trigger an iUPD. Unlike under RECIST 1.1, however, the confirmatory assessment is decisive for final progression under iRECIST.
Regulatory References
- iRECIST guidelines for response criteria in trials testing immunotherapeutics – describes iUPD, iCPD, and their application in immunotherapy trials.
- RECIST guideline, Version 1.1 – provides the foundational framework for lesion and progression assessment.
- EMA Guideline on the clinical evaluation of anticancer medicinal products – situates standardized tumor assessment within drug development.