Histopathological Growth Patterns and Survival After Resection of Colorectal Liver Metastasis: An External Validation Study

Abstract

Background: After resection of colorectal cancer liver metastases (CRLM), 2 main histopathological growth patterns can be observed: a desmoplastic and a nondesmoplastic subtype. The desmoplastic subtype has been associated with superior survival. These findings require external validation.

Methods: An international multicenter retrospective cohort study was conducted in patients treated surgically for CRLM at 3 tertiary hospitals in the United States and the Netherlands. Determination of histopathological growth patterns was performed on hematoxylin and eosin-stained sections of resected CRLM according to international guidelines. Patients displaying a desmoplastic histopathological phenotype (only desmoplastic growth observed) were compared with patients with a nondesmoplastic phenotype (any nondesmoplastic growth observed). Cutoff analyses on the extent of nondesmoplastic growth were performed. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier and multivariable Cox analysis. All statistical tests were 2-sided.

Results: In total 780 patients were eligible. A desmoplastic phenotype was observed in 19.1% and was associated with microsatellite instability (14.6% vs 3.6%, P = .01). Desmoplastic patients had superior 5-year OS (73.4%, 95% confidence interval [CI] = 64.1% to 84.0% vs 44.2%, 95% CI = 38.9% to 50.2%, P < .001) and DFS (32.0%, 95% CI = 22.9% to 44.7% vs 14.7%, 95% CI = 11.7% to 18.6%, P < .001) compared with their nondesmoplastic counterparts. A desmoplastic phenotype was associated with an adjusted hazard ratio for death of 0.36 (95% CI = 0.23 to 0.58) and 0.50 (95% CI = 0.37 to 0.66) for cancer recurrence. Prognosis was independent of KRAS and BRAF status. The cutoff analyses found no prognostic relationship between either OS or DFS and the extent of nondesmoplastic growth observed (all P > .1).

Conclusions: This external validation study confirms the remarkably good prognosis after surgery for CRLM in patients with a desmoplastic phenotype. The extent of nondesmoplastic growth does not affect prognosis.

Figure 1.

Hematoxylin and eosin–stained tissue sections of resected CRLM viewed at 5× magnification are shown with corresponding scale bars in the upper right. A) Hematoxylin and eosin–stained tissue section of a resected colorectal liver metastasis displaying a desmoplastic phenotype. Note the rim of desmoplastic tissue separating the tumor cells (lower right) from the liver parenchyma (upper left). B) Hematoxylin and eosin–stained tissue section of a resected colorectal liver metastasis displaying a nondesmoplastic phenotype. Note the absence of a desmoplastic rim and the direct contact between the tumor cells (lower left) and the liver parenchyma (upper right).

Figure 2.

Kaplan-Meier overall survival (OS) and disease-free survival (DFS) estimates are shown. Shown are OS (A) and DFS (B) estimates of patients with a desmoplastic vs a nondesmoplastic phenotype. Shown are OS (C) and DFS (D) estimates according to the extent of nondesmoplastic growth observed. The P values represent the results from the 2-sided log-rank tests used to compare the survival estimates.

Figure 3.

Kaplan-Meier overall survival (OS) and disease-free survival (DFS) estimates stratified by preoperative chemotherapy are shown. Shown are OS (A) and DFS (B) estimates for chemo-naive patients with a desmoplastic vs a nondesmoplastic phenotype. Shown are OS (C) and DFS (D) estimates for pretreated patients with a desmoplastic vs a nondesmoplastic phenotype. The P values represent the results from the 2-sided log-rank tests used to compare the survival estimates.