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FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study
Journal of Hematology & Oncology volume 15, Article number: 162 (2022)
No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0–14), intermediate risk (IR 15–17), and high risk (HR 18–28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.
To the Editor,
Risk-stratification screening efficiently reduces the incidence and mortality rate of colorectal cancer (CRC) , but no risk-stratification model has been extensively validated in China where the limited colonoscopy resources are mainly occupied by low-risk individuals with non-specific gastrointestinal symptoms (NSGS) [2, 3], who are considered equivalent to average-risk population for the risk of advanced colorectal neoplasia (ACN) [4, 5]. Current guidelines struggle to recommend to start colonoscopy screening at the age of 45 or 50 [6, 7]. However, any “one-size-fits-all” standard for age may prevent the detection of many early-onset CRCs [8, 9]. Herein, under the dilemma of inefficient detection, limited resources, and increasing early-onset CRC screening faced by colonoscopy practice, we developed and validated a risk-stratification model for colorectal neoplasia (CN).
From 2018 to 2020, the National Colorectal Polyp Care (NCPC) program was implemented in 175 centers nationwide (Fig. 1A), where consecutive adult individuals who had no alarming symptoms or signs of CRC were enrolled, regardless of NSGS . All participants completed questionnaires regarding baseline information and life risk factors and received fecal immunochemical tests (FITs) and colonoscopies. A central database was established to manage the uploaded data from all centers (accessed at www.ncrcgastro.org). The primary outcome was the CN . The details of methods, including exclusion criteria, outcome measures, sample size calculation, and statistical analysis, are illustrated in Additional file 1: Supplementary Methods.
A total of 10,164 participants were enrolled (Fig. 1B), whose clinical characteristics were comparable between the derivation and validation cohort (Additional file 2: Tables S1–2). The univariate analysis identified 11 potential risk factors, and eight variables (sex, age, body mass index, smoking, drinking, diabetes, first-degree relative of CRC, history of previous negative colonoscopy) were identified as independent predicting factors for developing NCPC score (Additional file 2: Table S3, Fig. 1C), while the other variables were excluded (Additional file 2: Table S4). The NCPC score was divided into three levels according to the mean CN prevalence: low risk (LR 0–14, 0–17.4%), intermediate risk (IR 15–17, 18.8–24.0%), and high risk (HR 18–28, ≥ 25.9%) (Additional file 2: Table S5). Compared with FIT- individuals, FIT+ individuals showed higher risks for CN, ACN, and CRC in all subgroups of NCPC score (all P < 0.001) (Additional file 2: Table S6). Therefore, the risk-stratification model (Changhai Li’s Model) triaged individuals with IR or HR NCPC scores or FIT+ as increased-risk individuals to receive colonoscopy.
The model showed good calibrations no significant difference of area under curve (AUC) between the derivation and validation cohort (0.68 vs. 0.68, P = 0.80); consistent predicting performance in risk-stratification ability and individuals’ distribution were confirmed in the deviation and validation cohort (Figs. 1D, 2A). No significant difference of AUC was also found between NSGS and asymptomatic population (0.68 vs. 0.67, P = 0.31), where the predicting performances were demonstrated to be similar; individuals’ distribution and prevalence of CN and ACN were also found to be consistent between NSGS and asymptomatic individuals (Figs. 1D, 2B).
Compared with FIT or other Asian models, the NCPC score showed the best discriminative ability for CN [0.67, P < 0.001] and ACN [0.70, P < 0.001 or = 0.002] [1, 11, 12] (Fig. 2C-E). The NCPC score could identify 70.7% CN, 77.7% ACN, and 78.7% CRC when reducing 29.2%, 35.5%, and 36.4% number needed for screening colonoscopies to detect one lesion (NNS), respectively (Fig. 2F). The risk-stratification model could identify 73.5% CN, 82.6% ACN, and 93.6% CRC when recommending 52.7% individuals to receive colonoscopy (Fig. 2F). By using risk-stratification model, only 25.6% young individuals will be recommended for colonoscopy, and 55.8% ACN and 72.7% CRC of young population could be identified when reducing 54.2% and 64.8% corresponding NNS, respectively (Fig. 2F).
In summary, a risk-stratification model (Changhai Li’s Model) for CN, consisting of FIT and NCPC score, was developed and validated to improve the efficiency of CRC screening. The model was able to save almost a half colonoscopy resources when maintaining a high sensitivity for CN, ACN, and CRC. Notably, 55.8% early-onset ACN and 72.7% early-onset CRC were identified with only 25.6% young individuals receiving colonoscopy. Consistent risk-stratifying performance was demonstrated between NSGS and asymptomatic population, which could rationally promote scope of CRC screening to cover the previously “ignored” NSGS population and avoid “indication gaming.” This model holds the promise as a feasible risk-stratification approach to improve the colonoscopy efficiency and CRC-screening scope in China and other countries with limited resources.
Availability of data and materials
All data related to the study are included in the paper and its supplementary materials.
Advanced colorectal neoplasia
Area under curve
Fecal immunochemical test
National Colorectal Polyp Care
Number needed for screening colonoscopy to detect one lesion
Non-specific gastrointestinal symptom
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We would like to thank the members of NCPC for enrolling participants in the study: Yingjian Zhang, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang; Qiong Nan, The First Affiliated Hospital of Kunming Medical University and Yunnan Institute of Digestive Disease, Kunming; Yali Wang, Third People’s Hospital of Datong, Datong; Zhilei Wu, Jiansanjiang People’s Hospital, Jiamusi; Guodong Yang, Affiliated Hospital of North Sichuan Medical College, Nanchong; Aibo Ma, Kunming First People’s Hospital of Yunnan Province, Kunming; Bing Hu, Eastern Hepatobiliary Surgery Hospital, Shanghai; Xing Chen, The First Hospital of Shanxi Medical University, Taiyuan; Shengyun Zhou, Xingtai People's Hospital, Xingtai; Ning Dai, Sir Run Run Shaw Hospital, Hangzhou; and all physicians from other participating centers (illustrated in Additional file 3: Supplementary lists).
Yu Bai is supported by the National Natural Science Foundation of China (Nos. 82170567, 81873546), Program of Shanghai Academic/Technology Research Leader (No. 22XD1425000), the “Shu Guang” project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 19SG30, China) and 234 Discipline Climbing Plan of Changhai Hospital, Naval Medical University (No. 2019YXK004, China). This work was also supported by the National Science and Technology Plan Project of the Ministry of Science and Technology of China (Grant No. 2015BAI13B08).
Ethics approval and consent to participate
The study protocol was approved by the Ethics Committee of the National Clinical Research Center for Digestive Disease (Shanghai, China). All participants provided signed informed consent. The NCPC program was registered in the ClinicalTrials.gov (NCT03712059).
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There is no conflict of interests for each author.
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Additional file 1.
Additional file 2.
Table S1. Clinical characteristics of participants and colonoscopy findings between the derivation and validation cohort; Table S2. Indications and quality indicators of colonoscopy between the derivation and validation cohort; Table S3. Univariate and multivariable analyses of variables included in the NCPC score based on the derivation cohort; Table S4. Univariate and multivariable analyses of variables excluded by the NCPC score based on derivation cohort; Table S5. Distribution of subjects, CN and ACN for each score category in the derivation and validation cohort; Table S6. CN risk stratified by NCPC score and FIT in the derivation and validation cohort.
Additional file 3
. Supplementary lists
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Zhao, S., Wang, S., Pan, P. et al. FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study. J Hematol Oncol 15, 162 (2022). https://doi.org/10.1186/s13045-022-01378-1
- Risk-stratification model
- Fecal immunochemical test
- Early-onset colorectal cancer
- Colorectal cancer screening