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Prognostic Significance of the Morphologic Features of Colorectal Adenocarcinoma Before and After Chemoradiotherapy
Maryam Shahi*3, Danielle M. Pastor4, Robert D. Madoff2, Alexander M. Truskinovsky1
1Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY; 2Surgery, University of Minnesota, Minneapolis, MN; 3Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN; 4Surgery, Albany Stratton VA Medical Center, Albany, NY
Background: The prognostic significance of the morphologic features of colorectal adenocarcinoma after chemoradiotherapy is not well understood. Post-chemoradiation carcinomas show tumor regression, stromal changes, and unusual tumor morphologies. We correlate the features of such tumors before and after chemoradiation with patient survival.
Design: We identified 20 patients with colorectal adenocarcinoma who underwent chemoradiotherapy or radiotherapy before the definitive surgery, and on whom both pre- and post-chemoradiation histologic tumor samples were available. We recorded tumor properties, either as continuous variables, or as features graded on a semiquantitative scale, and correlated them with survival. We also compared the tumor features of the patients who developed tumor recurrence or metastasis with those who did not.
Results: The mean patient age was 59 years (range, 46-89 years). There were 11 male and 9 female patients. Eighteen patients were treated with chemoradiation and 2 with radiation alone. All underwent proctocolectomy or abdominoperineal resection. All the tumors were colorectal-type adenocarcinomas, of which 2 had mucinous features and 1 showed focal squamous differentiation. In the resection specimens, the mean percentage of residual viable carcinoma in relation to the estimated pre-treatment tumor size was 29 (range, 1-80%). The pre-chemoradiation tumor features, seen in the initial biopsy, that were negatively associated with survival included high tumor grade (p=0.004), cytoplasmic vacuolation (p=0.003), bi- or multinucleation (p=0.0001), either completely absent or marked inflammation (p=0.025) and high tumor cellularity (p=0.002). Post-chemoradiation factors that were negatively associated with survival included high percentage of tumor necrosis (p=0.006), carcinoma in lymph nodes (p=0.017), tumor recurrence or metastasis (p=0.038), and increased patient age (p=0.034). The post-chemoradiation tumor grade, morphologic features of the neoplastic epithelium and evidence of tumor regression (fibrosis, xanthogranulomatous inflammation, hemosiderin deposition and calcification) showed no association with prognosis. Likewise, the pre-chemotherapy extent of the tumor, estimated from mural and nodal fibrosis or acellular mucin, had no correlation with survival. The patients who had tumor recurrence or metastasis differed from those who did not by having a higher pre-chemoradiation tumor mitotic rate (p=0.047).
Conclusion: Most tumor features that correlated with survival were those from before the treatment with chemoradiation, which may resonate with the current surgical tendency to forgo definitive surgery in favor of watchful waiting in some cases. Tumor vacuolation and bi- and multinucleation, which are currently not included in the standard histopathologic evaluation, had a strong correlation with survival.
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