Introduction

According to the current guidelines, all patients with lymph node metastases after curative surgery for colon cancer (CC) are recommended to undergo adjuvant chemotherapy, regardless of the T-stage. However, a limited number of patients with pT1-2 CC were included in the trials that demonstrated a benefit of adjuvant chemotherapy for lymph node positive CC patients. The aim of this study was to evaluate the value of adjuvant chemotherapy in patients with lymph node-positive pT1-2 CC.

Aims & Methods

A multicenter retrospective cohort study was conducted, including patients who underwent curative surgery for T1 or T2 CC between 2014 and 2015. Patients were originally identified through the Dutch ColoRectal Audit (DCRA), a prospective national registry of all patients undergoing surgery for primary colorectal cancer. Long-term oncological follow-up data from the original patient records were added to the DCRA data by surgical residents affiliated with the Dutch Snapshot Research Group (DSRG) from 61 participating hospitals. Patients were stratified by age (< 75 or ≥75 years). Survival outcomes were compared with the Kaplan-Meier method and log-rank test. Cox proportional hazard models were used to determine risk factors associated with 5-year metastasis-free and overall survival (MFS/OS).

Results

Among the 2277 surgically treated pT1-2 CC patients, 370 (16.2%) were found to have lymph node metastases, with 262 (70.8%) of them receiving adjuvant chemotherapy (CT+). Patients who did not receive adjuvant chemotherapy (CT-) were significantly older, had a higher ASA score, and experienced more frequently a complicated postoperative course, compared to the CT+ group. Among the total cohort, the vast majority of patients (78.6%) received oxaliplatin-based chemotherapy (CAPOX) and 13% capecitabine monotherapy. Among those under < 75 years old (n = 272), CAPOX was administered in 86.3% of cases, whereas in patients ≥ 75 (n = 97), capecitabine monotherapy was given in 42.9% and CAPOX in 38.1%. In younger patients (< 75), chemotherapy significantly improved OS (68.2% CT-group versus 91.8% in CT+ group, multivariate HR 0.3, 95% CI 0.1 ─ 0.6) and also had a favorable effect on MFS (83.7% in CT-group versus 91.6% in CT+ group, multivariate HR 0.5, 95% CI 0.2 ─ 1.09). In elderly patients (≥75 years old), the administration of adjuvant chemotherapy did not significantly affect the development of distant metastases (MFS of 81.7% in the CT- group versus 84.5% in the CT+ group, log rank p value 0.73, adjusted HR 1.2, 95% CI 0.4 – 3.8)), nor survival after correction for confounders (OS of 52.7% in the CT-group versus 77% in the CT+ group, age adjusted HR 0.6, 95% CI 0.2 ─ 1.5). The choice of chemotherapy regimen (CAPOX or capecitabine monotherapy) had no influence on MFS (HR 0.6, 95% CI 0.1 ─ 3.5) or OS (0.6, 95% CI 0.1 – 2.7).

Conclusion

In the largest cohort of node-positive pT1-2 colon cancer patients currently available, no significant benefit of adjuvant chemotherapy in patients over 75 years of age could be demonstrated, irrespective of the regimen that is chosen.

Introduction

Recently, some guidelines recommend conducting colorectal cancer (CRC) screening at ages younger than 50 years. However, there are few data on the preventive effect of colonoscopy at ages 40-49 years at the population level.

Aims & Methods

In this study, the risk of CRC according to the presence or absence of CSP in their 40s was evaluated in a retrospective cohort design using a nationwide database. Using the Korean National Health Insurance System data between 2004 and 2006, we constructed 1:5 colonoscopy cohort (CsC) and non-colonoscopy cohort (NCsC) at ages 40-49 years and followed through 2014. A total of 2,940,792 subjects were enrolled and CRC risk was evaluated after propensity score matching between CsC and NCsC based on age, sex, smoking, metabolic syndrome (MetS) and potentially relevant variables related CRC risk.

Results

Among 490,132 CsC subjects and 2,450,660 NCsC subjects at baseline periods in 40-49 ages, 689 (0.14%) and 9,440 (0.39%) cases of CRC were found during 10 years follow up period, respectively. According to age group, cumulative CRC incidences in early 40’s (40-44) were 0.10% in CsC and 0.25% in NCsC respectively. For late 40’s (45-49), those were 0.17% in CsC group and 0.49% in NCsC group, respectively. Compared with NCsC, the adjusted hazard ratios (aHRs) for CRC development in CsC group were 0.42 (men, 95% CI: 0.35-0.50) and 0.37 (women, 95% CI: 0.30-0.47) in early 40’s and 0.33 (men, 95% CI: 0.29-0.37) and 0.39 (women, 95% CI: 0.33-0.45) in late 40’s.

Conclusion

Overall, colonoscopy in their 40s significantly lowered the risk of colorectal cancer development by 58-67%. This cancer prevention effect of colonoscopy was different according to age and gender, and it was most effective in men in their late 40s, suggesting the rationales for optimization of age and gender to start colonoscopy.

Disclosure

Korea Health Technology R&D Project through the Korea Health Industry Development Institute, National Research Foundation of Korea grant and the National R&D Program for Cancer Control through the National Cancer Center funded by the Korea Ministry of Health & Welfare, Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education.

Introduction

At present, for the average risk population, colonoscopy surveillance intervals are based on previous detected and resected polyps in an individual. Although an inverse association between the endoscopist’s adenoma detection rate (ADR) and the risk of developing post colonoscopy colorectal cancer (PCCRC) is widely recognized, performance measures of endoscopists are not taken into account when deciding on surveillance intervals. This study aims to evaluate how the individual endoscopist’s ADR compares to the presence of high-risk polyps when evaluating the risk of PCCRC in the 3 years following a complete screening colonoscopy.

Aims & Methods

Data of all complete colonoscopies in which no CRC was found, performed within the Dutch fecal immunochemical test (FIT) based CRC population screening program between 2014 and 2020, were used for this study. Data were linked to the Dutch cancer registry. Individuals were categorized into having high-risk polyps or no/low risk polyps based on the 2020 ESGE post-polypectomy colonoscopy surveillance guideline. ADR was calculated per endoscopist. Risk of PCCRC, defined as any CRC diagnosed 6 months after the index colonoscopy, within 3 years was evaluated with shared frailty cox proportional hazard regression analysis in which ADR and presence of high-risk polyps were utilized as independent variables. Secondary, endoscopists were categorized into three equal groups based on ADR (low/medium/high) to enable stratified analysis.

Results

In total 239.217 individuals were included of which 74.289 (31.1%) had high-risk polyps at baseline and 202 had PCCRC in the subsequent 3 years. Median ADR of the 441 endoscopists involved was 66.3% (IQR 61.4-69.9). Cumulative incidence of PCCRC was 2.66 (95%CI 2.21-3.11, table 1) per 10.000 person-years of follow-up in individuals with no or low-risk polyps and 2.54 (95%CI 1.92-3.15) in individuals with high-risk polyps. Presence of high-risk polyps was not associated with risk of PCCRC (HR 1.00; 95%CI 0.75-1.35), while ADR was associated (HR 0.94 per point increase in ADR; 95%CI 0.92-0.96). The cumulative incidence of PCCRC was 3.68 (95%CI 2.74-4.62, table 1) per 10.000 person-years of follow-up for individuals with no or low-risk polyps that were treated by an endoscopist with low ADR, as compared to 1.69 (95%CI 0.89-2.50) for individuals with high-risk polyps treated by an endoscopist with high ADR (HR 2.11; 95%CI 1.21-3.65). Individuals with high-risk polyps treated by an endoscopist with low ADR had the highest risk of PCCRC, while individuals with no or low-risk polyps treated by an endoscopist with high ADR had the lowest risk (HR 3.30; 95%CI 1.79-6.10).

Table 1: Cumulative incidence and stratified risk of ADR/presence of high-risk polyps on post colonoscopy colorectal cancer

Conclusion

We demonstrated that in the Dutch FIT-based CRC population screening program, the ADR of the endoscopist has a major impact on relative risk of PCCRC within 3 years after a complete colonoscopy, while the presence of high-risk polyps does not. This underscores the significant impact of quality of colonoscopy on the short-term development of PCCRC and undermines the current surveillance guidelines that rely solely on polyp features.

Introduction

Long-term colorectal cancer (CRC) incidence and mortality after a negative colonoscopy screening remains unclear.

Aims & Methods

We aimed to assess CRC incidence and mortality in individuals with a negative colonoscopy screening according to CRC risk profiles.
We prospectively assessed colonoscopy screening, risk factors, and CRC diagnosis and death among 146,153 women from the Nurses’ Health study I/II and 33,538 men from the Health Professionals Follow-up Study between 1986 and 2017. We compared the CRC incidence and mortality for up to 20 years using Cox regression between individuals with the first reported negative colonoscopy screening and those without colonoscopy screening. We then assessed CRC risk in the negative screening group according to a CRC risk score (range, 0-8) defined by family history, smoking status, body mass index, height, physical activity, alcohol consumption, aspirin use, and diet, including the factors: red meat, processed meat, dietary fiber, dairy products and whole grain.

Results

During a median follow-up of 14 years (interquartile range, 8-20), we documented 1,766 and 436 CRC cases, and 586 and 126 CRC deaths, among participants with no screening and negative screening, respectively. Compared to individuals with no screening, those with a negative screening finding had a stable lower risk, with the multivariable hazard ratio (HR) (95%CI) at 20 years of 0.53 (0.46-0.58) for CRC incidence and 0.42 (0.34-0.51) for CRC mortality. The risk reduction was more substantial for rectal cancer (HR=0.32) and distal colon cancer (HR=0.42) than proximal colon cancer (HR=0.70) (P_{heterogeneity} <0.001). Among individuals with negative screening, we observed a nearly twofold elevation of CRC risk comparing the high-risk (score=5-8) with low-risk (score=0-2) groups (HR=1.99, 95%CI, 1.50-2.63, P_trend <0.001); and using the CRC incidence in the high-risk group at 10 years as the benchmark for surveillance, the low-risk group did not attain the benchmark until ~20 years after screening.

Conclusion

Individuals with a negative colonoscopy screening had a persistent lower risk of CRC incidence and mortality for at least 20 years and may extend their surveillance interval beyond the currently recommended 10 years, depending on their CRC risk factor profile.

Disclosure

Andrew T. Chan has served as a consultant for Bayer Healthcare and Pfizer for work unrelated to the topic of this manuscript. The remaining authors disclose no conflicts.