Multicenter validation study of pathologic response and tumor thickness at the tumor‐normal liver interface as independent predictors of disease‐free survival after preoperative chemotherapy and surgery for colorectal liver metastases

Abstract

Purpose To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). Patients and Methods One hundred seventy one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response defined as proportion of tumor cells remaining (categorized complete (0%), major (<50%) or minor (≥50%)) and tumor thickness at tumor–normal liver interface (TNI) (categorized <0.5 mm, 0.5 mm-<5 mm and ≥5 mm)—were assessed by a central pathology reviewer and local pathologists. Results Pathologic response was complete in 8%, major in 49% and minor in 43%. Tumor thickness at the TNI was <0.5 mm in 21%, 0.5 mm-<5 mm in 56% and ≥5 mm in 23%.In multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P=.002,.009), tumor thickness at TNI (P=0.015, <.001), duration of preoperative chemotherapy(P=.028,.043), number of CLM (P=.038,.037) and margin (P=.011,.016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P=.004,.015), duration of preoperative chemotherapy(P=.025), number of nodules(P=.027) and margin(P=.014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ=.82) and substantial agreement (κ=.76) for tumor thickness between central reviewer and local pathologists. Conclusion Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM.

Tumor histopathology predicts outcomes after resection of colorectal cancer liver metastases treated with and without pre-operative chemotherapy

“…The main findings of this study further clarify the influence of pathologic tumor viability and fibrosis on long-term outcomes after resection of CRCLM among patients treated and not treated with preoperative chemotherapy. The proportion of patients with a complete pathologic response to pre-operative chemotherapy in our study was 9.5%-within the range observed in other reports [1][2][3][4]6,8,14]. Among patients treated with pre-operative chemotherapy, there was a trend to lower median TRG (and thus greater proportion of fibrosis relative to viable tumor) among patients with compared to those without a RECIST response (Table III).…”

Pathological factors and prognosis of resected liver metastases of colorectal carcinoma: implications and proposal for a pathological reporting protocol

“…Tumour thickness correlated with pathological response ( P < 0.0001), with greater thickness (≥5 mm) predicting shorter recurrence‐free survival in multivariate analysis ( P = 0.015). Despite the difficulties in routine clinical practice, this method has been demonstrated to be reproducible …”

“…Despite the difficulties in routine clinical practice, this method has been demonstrated to be reproducible. 70,95,96 Sebagh et al 97 proposed a new method using a formula that considers the percentage of tumour cells and the size of all nodules. The sum of residual tumour was classified as follows: 0 residual tumour; 1-60 mm of residual tumour; and >60 mm of residual tumour.…”

Surgery for colorectal liver metastases: The evolution of determining prognosis

“…The "best" OS was, however, noted among those patients in whom all CRLM lesions showed a complete response [85] . Tumor regression grading, as well as tumor thickness at the tumor-normal interface, have been proposed as prognostic histopathological factors [83][84][85][86][87][88][89][90] . Based on the tumor regression scheme proposed for esophageal carcinoma, Rubbia-Brandt et al [90] described a pathological grading system for CRLM [90] .…”