How are modified RECIST (mRECIST) and immune RECIST (iRECIST) criteria applied to assess response in hepatocellular carcinoma (HCC)?

mRECIST and iRECIST for HCC Assessment

For HCC response assessment, RECIST v1.1 should be the primary criterion in clinical trials of systemic therapy, with mRECIST and iRECIST reported only as secondary assessments where appropriate 1. However, mRECIST is the standard tool for assessing response to locoregional therapies 1.

Key Differences and Applications

mRECIST (Modified RECIST)

mRECIST measures the largest diameter of viable, contrast-enhanced tumor rather than total tumor size, addressing the fact that locoregional therapies induce extensive tumor necrosis without immediate shrinkage 1.

When to use mRECIST:

• Locoregional therapies (ablation, TACE, SIRT): mRECIST is the standard, showing strong correlation with OS (HR 0.39 for responders vs non-responders, p<0.0001) 1
• Systemic therapies: Not recommended as primary criterion despite higher response rates, because:
  • Progression is captured similarly by RECIST v1.1 and mRECIST (no difference in TTP/PFS) 1
  • RECIST v1.1 is easier to use with better interobserver agreement 1
  • All pivotal trials of approved systemic therapies used RECIST v1.1 1
  • Recent data shows mRECIST did not improve OS prediction over RECIST v1.1 for immunotherapy 2

iRECIST (Immune RECIST)

iRECIST was designed to capture atypical responses to immunotherapy, particularly pseudoprogression 3.

Key iRECIST concepts:

• iUPD (unconfirmed progressive disease): Initial progression by RECIST v1.1 criteria that requires confirmation
• iCPD (confirmed progressive disease): Progression confirmed 4-8 weeks after iUPD by:
  • Further increase in target lesions ≥5 mm from iUPD 3
  • Additional new lesions or growth of existing new lesions 3
  • Further increase in non-target disease 3
• Status can reset: Unlike RECIST v1.1, patients can achieve iCR, iPR, or iSD after iUPD if subsequent imaging shows response 3

Critical limitation for HCC: iRECIST has not been properly evaluated in HCC 1. The 2025 EASL guidelines explicitly state this, and recent evidence confirms that iRECIST did not provide meaningful improvements in predicting OS benefits over standard RECIST v1.1 in HCC patients treated with immunotherapy 2.

Clinical Decision Algorithm

For locoregional therapy (ablation, TACE, SIRT):

• Use mRECIST as primary criterion
• Measure viable (contrast-enhancing) tumor only
• Strong OS correlation validates this approach

For systemic therapy (TKIs, immunotherapy):

• Use RECIST v1.1 as primary criterion
• May report mRECIST as secondary endpoint
• Do not rely on iRECIST for clinical decisions in HCC

If considering treatment beyond progression:

• Patient must be clinically stable 1, 3
• Confirm progression with repeat imaging 4-8 weeks later
• This applies regardless of which criteria triggered initial progression

Common Pitfalls

Avoid these errors:

• Using mRECIST as primary criterion for immunotherapy evaluation—it captures higher response rates due to vascular effects but doesn't improve survival prediction 1, 2
• Assuming iRECIST is validated for HCC—it is not, despite being designed for immunotherapy 1
• Stopping effective immunotherapy at first sign of progression without confirmation—pseudoprogression exists but must be balanced against delaying salvage therapy 3
• Measuring total tumor diameter instead of viable tumor when using mRECIST for locoregional therapy

The heterogeneity in contrast enhancement in advanced HCC makes RECIST v1.1 more reliable than mRECIST for systemic therapies, as it avoids subjective interpretation of viable versus necrotic tissue 1.