Tumor Regression Grading After Preoperative Chemoradiotherapy for Rectal Carcinoma Predicts Distant Metastasis Risk and Disease-Free Survival
In a study reported in the Journal of Clinical Oncology, Fokas et al found that prospectively evaluated tumor regression grading was a significant prognostic factor for distant metastasis and disease-free survival after 132 months of follow-up in patients with locally advanced rectal carcinoma treated with preoperative chemoradiotherapy in the German Cancer Society CAO/ARO/AIO-94 trial. The investigators had previously reported similar findings after a median follow-up of 41 months.
Study Details
The CAO/ARO/AIO-94 (Working Group of Surgical Oncology/Radiation Oncology/Medical Oncology of the German Cancer Society) trial demonstrated the superiority of preoperative vs postoperative chemoradiotherapy for local disease control, treatment compliance, and toxicity profile.
In the current analysis, tumor regression grade after preoperative chemoradiotherapy was determined in 386 surgical specimens by the amount of viable tumor cells vs fibrosis as tumor regression grade 4 (total regression, no viable tumor cells; n = 40), 3 (> 50% regression, dominant fibrosis outgrowing tumor mass; n = 203), 2 (moderate regression, dominant tumor mass with obvious fibrosis in 26%–50% of tumor mass; n = 53), 1 (minor regression, dominant tumor mass with obvious fibrosis in ≤ 25% of tumor mass; n =58), and 0 (no signs of regression; n = 32).
The 5-point tumor regression grading system was separated into three groups to avoid small categories, consisting of complete regression (tumor regression grade 4), intermediate regression (tumor regression grades 2 and 3), and poor regression (tumor regression grades 0 and 1). Clinicopathologic parameters and tumor regression grade were analyzed for association with cumulative 10-year incidence of local recurrence, distant metastasis, and disease-free survival.
Prognostic Ability
Ten-year cumulative incidences of local recurrence, distant metastasis, and disease-free survival were 2.6%, 10.5%, and 89.5% for patients with tumor regression grade 4 (complete regression); 8.0%, 29.3%, and 73.6% for tumor regression grades 2 and 3 (intermediate regression); and 3.6%, 39.6%, and 63.0% for tumor regression grades 0 and 1 (poor regression), respectively (P = .410, P = .005, and P = .008, respectively, for trends).
On multivariate analysis including numerous variables found significant on univariate analysis, variables significantly associated with 10-year outcomes consisted of ypN category (P < .001) and lymphatic invasion (P = .026) for local recurrence, ypN category (P < .001) and tumor regression grade (hazard ratio [HR] = 0.74, P = .035) for distant metastasis, and ypN category (P < .001) and tumor regression grade (HR = 0.76, P = .039) for disease-free survival.
The investigators concluded, “Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative [chemoradiotherapy] independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.”
Emmanouil Fokas, MD, DPhil, of University of Frankfurt, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by a German Cancer Aid (Deutsche Krebshilfe) grant. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
