Abstract
BackgroundMany factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs.MethodsWe performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials.ResultsBoth major histopathologic response (tumour regression grade TRG1–2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033).In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p < 0.001) and an unsignificant advantage from cetuximab vs bevacizumab was evident in RFS (p = 0.116). In the pushing HGP (N = 66), a significant benefit from bevacizumab vs cetuximab (p = 0.017) was observed. No difference was described in the replacement HGP (N = 65, p = 0.615).ConclusionsThe histopathologic response is the only independent determinant of survival in patients resected after triplets plus a biologic. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than cetuximab. The assessment of HGPs should be further explored as a predictor of benefit from available targeted agents.
Highlights
The management of metastatic colorectal cancer patients with liver-limited disease (LLD) is an intriguing challenge for oncologists, as the optimal integration of systemic and locoregional treatments may maximise survival outcomes and even cure a selected subgroup of patients
Up today no conclusive data about the differential impact of bevacizumab vs anti-EGFRs on tumour regression grade (TRG) were provided, since available series are affected by several bias, including an inappropriate molecular selection of patients treated with anti-EGFRs, and the adoption of heterogeneous chemotherapy backbones.[18,19]
Drawing from these considerations, we performed an extensive histopathologic evaluation of colorectal cancer liver metastases (CRCLM) resected after triplets and either bevacizumab or cetuximab, aiming at evaluating differences in histopathologic parameters of response according to administered targeted agents, assessing the independent prognostic impact of histopathologic parameters, and exploring the potential prognostic or predictive role of Histopathologic growth patterns (HGPs)
Summary
Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), their relative weight is unclear. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs. METHODS: We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than cetuximab.
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