Prognostic Significance of Tumor Regression After Preoperative Chemoradiotherapy for Rectal Cancer

TLDR

The study assessed the prognostic impact of tumor regression grading (TRG) in rectal cancer patients treated with preoperative chemoradiotherapy. TRG was determined from surgical specimens of 385 patients who received 50.4 Gy chemoradiotherapy with fluorouracil, followed by surgery six weeks later, and graded from TRG 4 (no viable tumor) to TRG 0 (no fibrosis) based on viable tumor versus fibrosis. TRG 4, 3, 2, 1, and 0 were observed in 10.4 %, 52.2 %, 13.8 %, 15.3 %, and 8.3 % of specimens, and five‑year disease‑free survival was 86 % for TRG 4, 75 % for TRG 2 + 3, and 63 % for TRG 0 + 1, with pathologic T category and nodal status being the strongest independent prognostic factors, indicating that complete and intermediate responses predict improved DFS and warrant prospective validation.

Abstract

We assessed the impact of tumor regression grading (TRG) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT).TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial: 50.4 Gy was delivered, fluorouracil was given in the first and fifth week, and surgery was performed 6 weeks thereafter. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 0 when fibrosis was completely absent. TRG 3 was defined as regression more than 50% with fibrosis outgrowing the tumor mass, TRG 2 was defined as regression less than 50%, and TRG 1 was defined basically as a morphologically unaltered tumor mass. We performed an initially unplanned, hypothesis-generating analysis with respect to the prognostic value of this TRG system.TRG 4, 3, 2, 1, 0 was found in 10.4%, 52.2%, 13.8%, 15.3%, and 8.3% of the resected specimens, respectively. Five-year disease-free survival (DFS) after CRT and curative resection was 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 (P = .006). On multivariate analysis, the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS.In this exploratory analysis, complete (TRG 4) and intermediate pathologic response (TRG 2 + 3) suggested improved DFS after preoperative CRT. TRG assessment should be implemented in pathologic evaluation and prospectively validated in further studies.