Preoperative predictors for pathologic response and prognosis of rectal cancer after neoadjuvant chemoradiation
Authors: G. Yoo, J. Yu, H. Park, D. Choi, W. Cho, Y. Park, J. Park, H. Lim, W. Kang, H. Kim, K. Song
Journal: Annals of Oncology (2018)

Introduction: A watch-and-wait approach following neoadjuvant chemoradiation (NCRT) could avoid the morbidity of surgery for rectal cancer. To determine which patients would be candidates of watch-and-wait approach, it is important to identify reliable factors predictive for the poor responses after the chemoradiation. In this study, we aimed to identify factors associated with pathologic response and long-term disease control. Methods: We retrospectively reviewed 353 patients who received NCRT and surgical resection. Patients who did not have magnetic resonance imaging (MRI) before and after NCRT (N = 161) and those who did not undergo total mesorectal excision were excluded (N = 13). Finally, 179 patients were included in the analyses. The dose regimen of NCRT was median 44 Gy (range, 34.4 to 60.0 Gy) in 22 fractions (range, 12 to 30 fractions). Among the total cohort, adjuvant chemotherapy was undergone in 160 patients. We evaluated both tumor regression grade (TRG) in MRI (mrTRG) and pathologic TRG (pTRG). Results: The median follow-up was 71 months (range, 6 to 101 months). The median age was 56 years (range, 27 to 81 years). Twenty-four patients were with cT1-2 disease, 150 with cT3 and 5 with cT4 disease. Twenty-two patients had cN0 disease. The median value of carcinoembryonic antigen (CEA) before and after NCRT were 2.19 ng/mL (range, 0.50 to 88.00 ng/mL) and 1.53 ng/mL (range, 0.40 to 12.79 ng/mL), respectively. Overall survival (OS), local control (LC), and disease-free survival (DFS) rates at 5 years were 84.8%, 91.2%, and 73.5%, respectively. The mrTRG 1 or 2 were achieved in 41 patients (22.9%). Pathologic complete responses (pCR; pTRG 4) were observed in 43 patients (24.0%). Among the patients with pCR, 37 patients achieved mrTRG 1 or 2. On multivariate analysis, mrTRG (1, 2 vs. 3, 4, 5; P = 0.005), ΔCEA, that is post-NCRT CEA minus pre-NCRT (< 0.33 vs. ≥ 0.33 ng/mL; P = 0.004), and circumferential margin (CRM) on MRI (mrCRM; P = 0.001) were identified as independent factors associated with DFS among the preoperative parameters. The DFS rates were significantly discriminated along the risk groups defined according to the number of the risk factors (mrTRG ≥ 3, ΔCEA ≥ 0.33 ng/mL, mrCRM) with 84.7% in low risk group (0 risk factor), 76.1% in intermediate risk group (1 risk factor), and 44.1% in high risk group (2 or more risk factors; P < 0.001). For OS, mrCRM (P < 0.001) and ΔCEA (P < 0.001) showed significantly association on the multivariate analysis. Among the patients with mrTRG 1, pTRG 3 or 4 was achieved in 70.7% of the patients. However, 60% of the patients who showed mrTRG grade 1 or 2 with post-NCRT CEA ≥ 3 ng/mL showed poor pTRG less than minimal response. Conclusion: The mrTRG, ΔCEA, and mrCRM were preoperative factors predicting the DFS, significantly. Although good mrTRG seems to be correlated with good pTRG, increased post-NCRT CEA might be associated with poor pTRG, even for patients with good mrTRG.