Hai-Yang Chen1,2, Li-Li Feng1,2, Ming Li3, Huai-Qiang Ju4, Yi Ding5, Mei Lan6, Shu-Mei Song7, Wei-Dong Han8, Li Yu8, Ming-Biao Wei1,2, Xiao-Lin Pang1,2, Fang He1,2, Shuai Liu1,2, Jian Zheng1,2, Yan Ma1,2, Chu-Yang Lin9, Ping Lan2,10, Mei-Jin Huang2,10, Yi-Feng Zou2,10, Zu-Li Yang2,10, Ting Wang2,10, Jin-Yi Lang6, Guy R Orangio11, Vitaliy Poylin12, Jaffer A Ajani7, Wei-Hu Wang13, Xiang-Bo Wan1,2. 1. Department of Radiation Oncology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. 2. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China. 3. Department of Radiation Oncology, Beijing Hospital/ National Center of Gerontology, Beijing, People's Republic of China. 4. Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. 5. Department of Radiation Oncology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, People's Republic of China. 6. Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, Sichuan, People's Republic of China. 7. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 8. Department of Medical Oncology, Sir Run Run Shaw Hospital of College of Medicine Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. 9. Department of Clinical Skills Training Center, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China. 10. Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. 11. Section of Colon and Rectal Surgery, LSU Department of Surgery, LSU School of Medicine, New Orleans, Louisiana, USA. 12. Division of Colon & Rectum Surgery, Department of Surgery, Beth Israel Deaconess Medical Center of Harvard Medical School, Boston, Massachusetts, USA. 13. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
Abstract
BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.
BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.
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