What does a TRG (Tumor Regression Grade) 1 indicate in terms of response to cancer treatment in a patient with inadequate response to initial therapy?

Understanding TRG 1 (Tumor Regression Grade 1) and Inadequate Response

TRG 1 in the Mandard classification system indicates a complete pathologic response (pCR) with no residual cancer cells—this represents an EXCELLENT response, not an inadequate one. 1

Critical Clarification: TRG Scoring Systems Vary

The confusion in your question stems from different TRG classification systems using opposite numbering schemes:

Mandard System (Most Common)

• TRG 1 = Complete response (no residual cancer cells) 1
• TRG 2 = Rare residual cancer cells 2
• TRG 3 = Increased cancer cells but fibrosis predominating 2
• TRG 4-5 = Minimal or no response 1

Dworak System (Alternative)

• TRG 1 = Minimal regression 1
• TRG 5 = Complete response 1

The ESMO guidelines explicitly state that pCR is classified by Mandard as TRG1 but by Dworak as TRG5, highlighting the lack of standardization. 1

What Actually Constitutes "Inadequate Response"

In Mandard System (Standard)

An inadequate response would be TRG 3-5, NOT TRG 1. 3, 2

• TRG 3-5 patients show significantly worse outcomes:
  • 5-year disease-free survival: 58% vs. 91% for TRG 1-2 3
  • 5-year overall survival: 68% vs. 89% for TRG 1-2 3
  • Local failure rate: 17% vs. 2% for TRG 1-2 3

Clinical Implications by TRG Category

For TRG 1-2 (Good Responders):

• 92% 5-year overall survival 2
• 75% 5-year disease-free survival 2
• May be candidates for less aggressive surgical approaches 3
• In rectal cancer, TRG 0 (complete response) patients may not require adjuvant chemotherapy 4

For TRG 3-5 (Poor Responders):

• 48% 5-year overall survival 2
• 39% 5-year disease-free survival 2
• Require standard radical surgery 3
• Should receive adjuvant chemotherapy 4
• May benefit from alternative treatment strategies 2

Prognostic Significance

TRG is an independent predictor of disease-free survival by multivariate analysis, along with pathologic nodal status. 3

• TRG predicts local failure (p=0.013), metastasis-free survival (p=0.004), and overall survival (p=0.004) 3
• TRG correlates with pathologic nodal involvement (p<0.0001), helping identify patients at higher risk 3
• Each TRG category (0,1,2,3) has statistically distinct survival outcomes 4

Common Pitfall: Misinterpreting the Grading System

Always verify which TRG system your pathology department uses—Mandard vs. Dworak—as they assign opposite numerical values to the same histologic findings. 1 The ESMO guidelines recommend that at minimum, tumors should be graded as complete response, partial response, or no response to avoid confusion 1.