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Anatomical and Histologic Response to Neoadjuvant Therapy: Recurrence Patterns Among Poor Responders. A
Andrea Baldo1,2, Miho Akabane1, Abdulaziz Elemosho1
1Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.
Annals of Surgery
|July 20, 2026
Summary
Combining anatomical (Tumor Burden Score ratio) and histologic (Tumor Regression Grade) response effectively predicts recurrence risk in patients undergoing hepatectomy for colorectal liver metastases (CRLM). This integrated approach offers a clear framework for stratifying patient outcomes.
Area of Science:
- Oncology
- Surgical Oncology
- Hepatobiliary Surgery
Background:
- Accurate response assessment to neoadjuvant therapy (NAT) is crucial for managing colorectal liver metastases (CRLM).
- Existing macroscopic and histologic assessment tools for NAT response have limitations in characterizing recurrence patterns.
- Integrating anatomical and histologic response metrics may improve prognostic accuracy for CRLM patients.
Purpose of the Study:
- To evaluate the prognostic significance of combining anatomical response (Tumor Burden Score ratio, TBSr) and histologic response (Tumor Regression Grade, TRG) after hepatectomy for CRLM.
- To develop a risk stratification framework integrating TRG and TBSr for predicting recurrence after CRLM resection.
- To analyze the impact of combined TRG-TBSr on recurrence-free survival (RFS) and recurrence patterns.
Main Methods:
- Retrospective analysis of 483 patients undergoing hepatectomy for CRLM post-NAT from an international database (2004-2022).
- Macroscopic response assessed by TBSr; histologic response by TRG (good: 1-3, poor: 4-5).
- TRG-TBSr patterns were grouped into risk categories using maximally selected log-rank statistics to predict RFS, recurrence timing, and intrahepatic recurrence.
Main Results:
- Both TRG and TBSr were independently associated with worse RFS (P<0.001).
- Early recurrence (<12 months) and intrahepatic recurrence were significantly predicted by both TRG and TBSr (P<0.001).
- Integrated TRG-TBSr risk categories demonstrated strong associations with RFS, early recurrence, and intrahepatic recurrence (all P<0.001).
Conclusions:
- The combination of anatomical (TBSr) and histologic (TRG) response assessment provides a simple, interpretable, and biologically meaningful framework.
- This integrated approach effectively stratifies recurrence risk in patients undergoing hepatectomy for CRLM.
- The TRG-TBSr model enhances prognostic accuracy for predicting outcomes after CRLM resection.