Introduction

Screen-detected colorectal cancers (CRCs) are often treated less invasively than stage-matched non-screen-detected CRCs, but the reasons for this are not fully understood. This study aimed to describe the treatment of stage I CRCs detected within and outside the CRC screening program in the Netherlands and to identify factors associated with treatment on population level.

Aims & Methods

Data from the Netherlands Cancer Registry of all stage I CRCs diagnosed between January 1, 2008 and December 31, 2020 were analyzed, comparing patient, tumor and treatment characteristics of screen-detected and non-screen-detected stage I CRCs. Multivariable logistic regression analyses were used to assess the association between treatment (local excision only vs. surgical oncologic resection) and patient and tumor characteristics, stratified for T-stage and tumor location.

Results

Screen-detected stage I CRCs were relatively more often T1 than T2 compared to non-screen detected stage I CRCs (66.9% versus 53.3%, p <0.0001). When only considering T1 tumors, both screen-detected colon and rectal cancers were more often treated with local excision only than non-screen detected T1 cancers (OR 2.19, 95%CI 1.93-2.49 and OR 1.29, 95%CI 1.05-1.59, respectively), adjusted for sex, tumor location, lymphovascular invasion (LVI) status and tumor differentiation (Table 1).

Conclusion

Less invasive treatment of screen-detected stage I CRC is partly explained by the higher rate of T1 compared with non-screen-detected stage I CRC. Those with T1 stage I CRCs were also more likely to undergo less invasive treatment if they were detected by screening, after adjusting for risk factors such as LVI and tumor differentiation.

Introduction

Colorectal cancer (CRC) screening has been implemented in numerous countries within the last two decades¹. There is strong evidence that CRC screening leads to enhanced disease free- and overall survival^2–6. However, there is to the best of our knowledge no studies investigating the effects of CRC screening on treatment in a long-term perspective.

Aims & Methods

The objective of this study was to investigate the effects of the Danish national CRC screening program on long-term treatment and health care contacts for patients diagnosed with CRC.This nationwide retrospective cohort study evaluated surgical- and oncological outpatient visits, treatments with chemo- and radiotherapy, health care contacts and hospitalization for patients with CRC during the first two years after diagnosis comparing patients with and without screen-detected CRC. The population consisted of Danish residents aged 50-75 years and diagnosed with CRC between January 1rst 2014 and March 31rst 2018. Data was collected from national healthcare registers .Duration of hospitalization were analyzed using a multivariate general linear model, metastasectomies and emergency surgeries were analyzed using a multivariate generalized linear model and data on oncological treatments were analyzed using a multivariate Poisson regression. Moreover, analyzes were stratified into UICC stages and adjusted for sex, 5-year age groups, type of cancer (colonic/rectal), and Charlson Comorbidity Index score to reduce healthy user bias.

Results

We included 4,708 and 7,332 patients with screen-detected CRC (SD-CRC) and non-screen-detected CRC (NSD-CRC), respectively. SD-CRC was associated with 38% reduced hospitalization. In a UICC-stratified analysis, hospitalization was shorter in the SD-CRC group across all UICC-stages. The rate of emergency surgery was significantly lower (RR=0.34, 95%-CI:0.28-0.41) in the SD-CRC group. There was no difference between the groups in rates of surgery for lung and liver metastasis. Lower number of oncological outpatient visits (RR=0.35, 95%-CI:0.33-0.37), treatment with chemotherapy (RR=0.57, 95%-CI:0.56-0.59) and radiotherapy (RR=0.50, 95%-CI:0.49-0.52) were found for patients with SD-CRC. UICC-stratified analyses revealed that these differences were consistent for all UICC stages, except for a significantly higher rate of treatment with chemotherapy in SD-CRC UICC stage IV. Overall, there was no difference between the two populations in number of contacts with primary healthcare providers. However, a UICC-stratified analysis revealed significantly fewer contacts with primary healthcare providers for patients with SD-CRC UICC I and III.

Conclusion

Compared with NSD-CRC, SD-CRC was associated with shorter hospitalization, less emergency surgery, and reduced oncological treatment within two years after diagnosis.

References

1. Schreuders EH, Ruco A, Rabeneck L, et al. Colorectal cancer screening: a global overview of existing programmes. 2014;67:643-650.
2. Spolverato G, Capelli G, Battagello J, et al. More favorable short and long-term outcomes for screen-detected colorectal cancer patients. Front Oncol. 2021;11:1-10.
3. Luu XQ, Lee K, Jun JK, Suh M, Jung KW, Choi KS. Effect of colorectal cancer screening on long-term survival of colorectal cancer patients: Results of the Korea National Cancer Screening Program. Int J Cancer. 2022;150:1958-1967.
4. Shaukat A, Mongin SJ, Geisser MS, et al. Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369:1106-1114.
5. Cienfuegos JA, Baixauli J, Martínez-Ortega P, et al. Screening-detected colorectal cancers show better long-term survival compared with stage-matched symptomatic cancers. Rev Esp Enfermedades Dig. 2018;110:684-690.
6. Losurdo P, Giacca M, Biloslavo A, et al. Colorectal cancer-screening program improves both short- and long-term outcomes: a single-center experience in Trieste. Updates Surg. 2020;72:89-96.

Introduction

Testicular cancer (TC) survivors treated with platinum-based chemotherapy have an increased risk for developing secondary colorectal cancer (CRC) [1]. Colonoscopy surveillance is offered to other high-risk survivors to reduce CRC incidence and mortality. We aimed to assess the yield of colonoscopy in TC survivors.
[1] Groot HJ, Lubberts S, de Wit R, Witjes JA, Martijn Kerst J, de Jong IJ, et al. Risk of Solid Cancer After Treatment of Testicular Germ Cell Cancer in the Platinum Era. J Clin Oncol. 2018;36:2504–13. Available from: https://doi.org/10.1200/JCO.2017.

Aims & Methods

We conducted a prospective multicenter primary colonoscopy screening study in four Dutch hospitals. The yield of colorectal neoplasia among TC survivors was assessed at primary colonoscopy. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs; high-grade dysplasia, ≥25% villous component, or ≥10mm diameter), advanced serrated polyps (ASPs; dysplasia or ≥10mm diameter), or CRC. Advanced neoplasia (AN) was defined as AA, ASP, or CRC. Yield of colonoscopy was compared to matched average-risk American males that underwent primary screening colonoscopy (n=24.193) and using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index.

Results

A total of 137 TC survivors underwent colonoscopy. Median age was 50 years among TC survivors (IQR 43-57) vs. 55 years (IQR 51-62) in American controls. The prevalence of any neoplasia and AN was higher in TC survivors compared to age-matched American controls (Table 1). Using propensity score matching the difference in the prevalence of AN between TC survivors and American controls was even larger (8.7% vs. 1.7%; p<0.0001).

Conclusion

TC survivors treated with platinum-based chemotherapy had a higher incidence of any neoplasia and AN compared with age-matched controls, which was underscored by the propensity score matching analysis. These results support our hypothesis that platinum-based chemotherapy increases the risk of developing colorectal neoplasia in TC survivors, emphasizing the importance of participation in CRC screening and clear risk communication.

Introduction

In Hungary, the population-based colorectal carcinoma (CRC) screening programme was introduced at the end of 2018, shortly before the start of the COVID-19 pandemic.

Aims & Methods

The aim of our retrospective cohort study was to evaluate the impact of two presumably opposing causal factors, COVID-19 pandemic and population-based screening, on the incidence and clinical characteristics of CRC. All patients with newly diagnosed CRC from 2014 to 2023 were included and categorized into pre-pandemic (confirmed between 2014-2019), pandemic (confirmed in 2020-2021) and post-pandemic (confirmed in 2022-2023) groups. The extended pre-pandemic period was required to assess the impact of the screening programme, further dividing it into screening-affected (2015, 2016, and 2019) and unaffected (2014, 2017, 2018) subgroups.

Results

A total of 2803 patients were diagnosed with CRC during the study period. The annual number of CRC cases was significantly lower in the pandemic subgroup compared to the pre-pandemic screened and post-pandemic subgroups (254/year, 295/year and 295/year, p=0.009). In addition, in the pandemic subgroup, the incidence rates of CRCs detected at localized stage were significantly lower compared to the other three groups (36.61%, 50.85%, 46.35% and 49.49%, p<0.001). Statistically significant difference in the rate of T1 tumors was only observed between the pandemic and the post-pandemic subgroups (7.09% and 12.20%, p=0.026). In the pandemic period, the annual number of colonoscopies decreased by 64.31% compared to the pre-pandemic period overall, however, the post-pandemic period (n=4574) saw a modest 8.70% increase relative to the pre-pandemic period, offering only partial compensation for the shortage experienced during the pandemic. Furthermore, the annual number of colonoscopies in the extended pre-pandemic subgroup with screening was higher by 20.06% compared to the pre-pandemic subgroup without screening (4591 examinations/year vs 3824 examinations/year) and it was almost the same as the post-pandemic subgroup (4574 examinations/year). Substantially fewer examinations were required to detect a CRC in the pandemic group compared to the pre-pandemic overall and post-pandemic groups (10.67, 15.56, 13.97 and 15.50 examinations, respectively), but within the extended pre-pandemic group, there was no relevant difference between the two subgroups in the mean number of colonoscopies required to detect a CRC (15.56 vs. 13.97).

Conclusion

Our study confirmed the negative impact of COVID-19 pandemic on the CRC epidemiology. The newly introduced population-based CRC screening has only been able to partially compensate this negative effect during pandemic period, however, was moderately compensated by during the pandemic period, but in the post-pandemic period it caused a favorable change in the clinical features of CRC. Our study demonstrates both the effectiveness of the screening programme and that by introducing non-invasive pre-screening of patients (e.g. iFOBT) in a pandemic situation, it can reduce its negative public health impact.

Introduction

There is growing evidence that the balance of harms and benefits of colorectal cancer (CRC) screening can be improved by risk stratification. One way to stratify participants is to assign a personalized invitation interval based on prior screening test results. Previous studies have shown that prior hemoglobin (Hb) concentrations determined by fecal immunochemical test (FIT), have greater predictive power for the detection of CRC in the next screening round than age and sex (1-3). Therefore, a randomized controlled trial, the PERFECT-FIT study (4), was initiated within the Dutch national CRC screening program in which participants with a prior negative FIT are invited using tailored invitation intervals (1,2 or 3 years) based on prior Hb concentrations. We aimed to investigate long-term outcomes of such personalized CRC screening based on prior Hb concentrations and to compare those to uniform CRC screening.

Aims & Methods

We simulated the Dutch national CRC screening program using a microsimulation model, MISCAN-Colon, to mimic the natural history of CRC and long-term outcomes of CRC screening interventions. We added a module to MISCAN-Colon that explicitly simulates a Hb concentration for every participant based on their age, sex, CRC state and an individual risk factor. Next, to mimic the PERFECT-FIT study, all participants with a negative FIT got assigned to either the low (0 µg Hb/g), intermediate (>0-15 µg Hb/g) or high (>15-<47 µg Hb/g) risk category. We evaluated different invitation intervals (ranging between 0.5 and 4 years) for each risk category and estimated short- and long-term effects of the different screening strategies. We compared each personalized screening strategy to uniform biennial screening. Using cost-effectiveness analysis with a willingness-to-pay threshold per QALY gained of €20,000,-, we determined optimal invitation intervals for each risk category, assuming (i) unlimited colonoscopy capacity and (ii) current colonoscopy capacity levels.

Results

Uniform biennial screening resulted in 177 QALYs gained and €101,852 saved compared to no screening per 1,000 individuals (Table 1). The PERFECT-FIT strategy resulted in 162 QALYs gained and €111,248 saved. The optimal invitation interval was 1 year for the low-risk group and 6 months for the intermediate and high-risk groups with 209 QALYs gained and €19,828 saved. With limited colonoscopy capacity, the optimal invitation interval changed to 2.5 years for the low-risk group, 1 year for the intermediate-risk group and 6 months for the high-risk group with 180 QALYs gained and €124,640 saved.

Table 1 Model outcomes per 1,000 individuals.

Conclusion

The optimal personalized CRC screening strategy is more cost-effective than uniform biennial screening, both with unrestricted and restricted colonoscopy capacity. Consequently, personalizing CRC screening invitation intervals based on prior FIT results may be an important next step to improve the balance between the harms and benefits of screening.

References

1. Grobbee EJ, Schreuders EH, Hansen BE, Bruno MJ, Lansdorp-Vogelaar I, Spaander MCW, et al. Association Between Concentrations of Hemoglobin Determined by Fecal Immunochemical Tests and Long-term Development of Advanced Colorectal Neoplasia. Gastroenterology. 2017;153(5):1251-9.e2.
2. Senore C, Zappa M, Campari C, Crotta S, Armaroli P, Arrigoni A, et al. Faecal haemoglobin concentration among subjects with negative FIT results is associated with the detection rate of neoplasia at subsequent rounds: a prospective study in the context of population based screening programmes in Italy. Gut. 2020;69(3):523-30.
3. Chen LS, Yen AMF, Chiu SYH, Liao CS, Chen HH. Baseline faecal occult blood concentration as a predictor of incident colorectal neoplasia: Longitudinal follow-up of a Taiwanese population-based colorectal cancer screening cohort. Lancet Oncol. 2011;12(6):551-8.
4. Breekveldt ECH, Toes-Zoutendijk E, de Jonge L, Spaander MCW, Dekker E, van Kemenade FJ, et al. Personalized colorectal cancer screening: study protocol of a mixed-methods study on the effectiveness of tailored intervals based on prior f-Hb concentration in a fit-based colorectal cancer screening program (PERFECT-FIT). Bmc Gastroenterology. 2023;23(1):1-10.