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

Patients with screen-detected colorectal cancer (CRC) have a better overall survival, compared to patients with non-screen detected CRC. Importantly, also the stage-specific survival is higher.¹ Suggested explanations for this improved survival in patients with screen-detected CRC are a higher curative treatment intent and less post-operative complications.^2,3 Furthermore, screen-detected CRCs may have more indolent tumor characteristics, which^4,5 may lead to less CRC recurrence and improved survival. The recurrence rates however, of screen-detected and non-screen detected CRCs are unknown. We aimed to compare recurrence rates in screen-detected and non-screen detected CRCs and related these to overall survival.

Aims & Methods

Patients diagnosed with stage I, II or III CRC in the first 6 months of 2015 were included. Data on stage, location, treatment, recurrence and survival were retrieved from the Netherlands Cancer Registry (NCR). Follow-up data was available until January 2021. Screen-detected CRCs were detected within the Dutch FIT-based CRC screening program. Non-screen-detected CRCs were clinically detected CRCs. CRCs detected through surveillance were excluded. Overall and stage-specific recurrence rates were analyzed in screen-detected and non-screen detected CRCs with Kaplan Meijer curves. The effect of recurrence on overall survival was evaluated with a Cox-regression model, adjusted for tumor characteristics (location, stage and substage), patient characteristics (gender and age) and treatment (radiotherapy and/or chemotherapy).

Results

In total, 3813 patients with were included, of whom 2144 (56.2%) were non-screen-detected and 1669 (43.8%) were screen-detected. Compared with non-screen-detected CRC, screen-detected patients were more often men (62.7% vs. 58.5%, p=0.009), and screen-detected CRCs were more often located in the left-sided colon (49.1% vs. 33.7%, p <0.001), and detected in early stages (I-II) (72.0% vs. 53.6%, p <0.001). The four-year CRC recurrence rate in screen-detected CRCs was significantly lower compared to patients with non-screen-detected CRCs (13% versus 21%, p <0.001). Stage-specific recurrence of CRCs after four years for screen-detected CRCs vs non-screen-detected cases were 5% vs. 6% for stage I (p=0.82); 14% vs. 17% for stage II (p=0.23) and 23% vs 33% (p<0.001) for stage III, respectively. Recurrence was an independent predictor for the 5-year overall survival in screen-detected cases (HR 7.65 [p<0.001]) and non-screen-detected cases (HR 6.60 [p <0.001]; adjusted for stage, gender, age, treatment and tumor location. The HR for recurrence for screen-detected CRC versus non-screen detected CRC was 0.68 (CI: 0.57 – 0.81, p <0.001) when adjusted for stage, gender, age, treatment and tumor location. When evaluated for each stage separately, the HR for recurrence was 0.98 (CI: 0.56-1.69, p = 0.93]) in stage I; 0.79 (CI: 0.56-1.13, p = 0.198) in stage II and 0.61 (CI 0.49-0.77, p <0.001) in stage III, respectively. Within stage III CRCs, detection in substage (3A, 3B, 3C) and surgical resection were independent predictors for recurrence. In this adjusted model, patients with screen-detected stage III CRC have less recurrence (HR 0.74, p =0.01) compared to non-screen detected patients.

Conclusion

Patients with screen-detected stage III CRCs had less recurrence than non-screen-detected stage III CRC patients. This result remains after adjustment for patient, tumor and treatment factors and could be explained by a different tumor biology.

References

1. Cardoso R, Guo F, Heisser T, De Schutter H, Van Damme N, Nilbert MC, Christensen J, Bouvier AM, Bouvier V, Launoy G, Woronoff AS, Cariou M, Robaszkiewicz M, Delafosse P, Poncet F, Walsh PM, Senore C, Rosso S, Lemmens VEPP, Elferink MAG, Tomšič S, Žagar T, Marques ALM, Marcos-Gragera R, Puigdemont M, Galceran J, Carulla M, Sánchez-Gil A, Chirlaque MD, Hoffmeister M, Brenner H. Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries. Lancet Reg Health Eur. 2022 Jul 6;21:100458.
2. Krul MF, Elferink MAG, Kok NFM, Dekker E, Lansdorp-Vogelaar I, Meijer GA, Nagtegaal ID, Breekveldt ECH, Ruers TJM, van Leerdam ME, Kuhlmann KFD. Initial Impact of National CRC Screening on Incidence and Advanced Colorectal Cancer. Clin Gastroenterol Hepatol. 2023 Mar;21(3):797-807.e3.
3. de Neree Tot Babberich MPM, Vermeer NCA, Wouters M, Dekker E, et al. Postoperative Outcomes of Screen-Detected vs Non-Screen-Detected Colorectal Cancer in the Netherlands. JAMA Surg. 2018;153(12): e183567.
   
4. Phipps AI, Limburg PJ, Baron JA. Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology. 2015 Jan;148(1):77-87.e2.
5. Kalady MF, Sanchez JA, Manilich E. Divergent oncogenic changes influence survival differences between colon and rectal adenocarcinomas. Dis Colon Rectum. 2009 Jun;52(6):1039-45.

Disclosure

Nothing to disclose.

Introduction

Colorectal cancer (CRC) screening reduces cancer risk, yet real-world adherence to screening remains variable. We aimed to leverage a large healthcare organization longitudinal cohort to evaluate factors that influence the timeliness of adherence to screening guidelines.

Aims & Methods

We included average-risk Maccabi Healthcare Services members aged 50–75 years who were alive on 1 January 2025. Demographics, comorbidities, hemoglobin values, and dates of fecal immunochemical test(FIT), CT-colonography (CTC) and colonoscopy were extracted.
Adherence was defined as annual FIT, colonoscopy every 10 years, or CTC every 5 years.
Patients covered for >50 % versus ≤50 % of follow-up time by screening guidelines were compared with Wilcoxon rank-sum (continuous) and χ²/Fisher’s exact (categorical) tests.
In order to study factors associated with adherence times, longitudinal adherence was modelled with a gap-time Andersen–Gill Cox regression. The dependent variable was time (in periods) to the recurrent event active adherence. Adjusted hazard ratios (HRs) and 95 % confidence intervals (CI) were estimated with robust variance, clustering on patient ID to account for within-subject correlation.

Results

Our cohort comprised 590,550 adults at screening age, contributing 6,581,044 person-years of follow-up. In a baseline comparison between individuals whose proportion of time covered was less than 50%(n=282,347) vs more than 50%(n=308,203), the latter group was older (60.00 [55.00, 68.00] years vs 62.00 [57.00, 67.00] years, p-value<0.001) with a longer median follow up (9.0 [4.0, 17.0] years vs 11.0 [6.0, 16.0] years, p-value<0.001). Higher prevalence of hypertension (17.5 % vs 12.0 %, p-value<0.001), diabetes mellitus (8.2 % vs 5.8 %, p-value<0.001), pre-diabetes (22.4 % vs 17.5 %, p-value<0.001), and cardiac disease (4.8 % vs 3.4 %, p-value<0.001) were seen among the more compliant group. Consistent with greater adherence, endoscopic referral was more common at baseline in the more compliant group (6.2 % vs 1.0 %, p-value<0.001). Interestingly. Although the differences in distributions of sector, district and socioeconomic rank categories were significant, the absolute percentage differences across strata were small and unremarkable (<3 percentage points for any category).
A gap-time survival model demonstrated that each additional year of age was associated with longer intervals and a lower aHR for active adherence (aHR 0.94, 95 % CI 0.94–0.94). Men undergone screening tests marginally sooner than women (aHR 1.05, 95% CI 1.04–1.05). Adherence was lower in the orthodox sector (aHR 0.84, 95% CI 0.84–0.85). Metabolic or cardiovascular conditions translated into earlier adherence: pre-diabetes (aHR 1.63, 95% CI 1.62-1.63), diabetes (aHR 1.54, 95% CI 1.54-1.55), hypertension (aHR 1.22, 95% CI 1.21-1.23), cardiac disease (aHR 1.14, 95% CI 1.14-1.15), and obesity (aHR 1.10, 95% CI 1.10-1.11). Severe conditions and subjects included in severe disease registry were associated with lower adherence (aHR 0.33, 95% CI 0.30-0.38; and aHR 0.63, 95% CI 0.59-0.67, respectively). Recent higher hemoglobin levels delayed active adherence (aHR 0.97 per each increase of 1 g/dL, 95% CI 0.97-0.98).

Conclusion

Our results suggest that long term compliance for CRC screening is related to age as well as for chronic medical conditions, particularly metabolic and cardiovascular. Screening efforts should therefore be aimed at healthy subjects or those with minor contact with medical providers.

Introduction

Colorectal cancer’s (CRC) incidence above 50 years old has been decreasing globally in the last decades, but its incidence in patients below 50 years old (early-onset colorectal cancer, EO-CRC) has been increasing, for reasons not yet fully understood.

Aims & Methods

A unicentric cohort study was conducted in a tertiary centre, including all patients admitted for a first diagnosis of CRC and evaluated by the Multidisciplinary Colorectal Cancer Group from 01.01.2017 until 31.12.2018. Patients with a previous diagnosis of a Hereditary Colorectal Cancer Syndrome were excluded.

Results

A total of 438 patients were included, 58.2% males, with a mean age at diagnosis of 67.7±11.1 years old. Mean follow-up time was 41.49 months. There were 25 EO-CRC patients (5.7%), 17 males (68%), mean age 43.1±6.0 years old.
Globally, 32.4% of the patients were current or past smokers, 18.5% had previous non-colorectal cancer, 7.5% and 3.4% were previously exposed to immunosuppressive drugs or abdominal/pelvic radiotherapy, respectively. The majority presented with normal(29.7%) to high Body Max Index (39.7%), median 25.6 (IQR:22.6-28.4) Kg/m². The most common CRC location was the rectum (42.9%) and 56.1% were stage I or II (AJCC 8^th edition).
In the univariate analysis, a significant association was found between EO-CRC and: smoking status (past or current smokers 52% in EO-CRC vs. 31.2% in older cases p=0.009); lymphovascular invasion (40.0% in EO-CRC vs. 17.4% in over 50, p=0.018) No significant differences were found for histological subtype (p=0.447), perineural invasion (p=0.474), or tumor stage at diagnosis, although a relevant proportion of the younger patients had metastatic disease at diagnosis (28.0% vs. 12.8%, p=0.064).
Immunohistochemistry for mismatch-repair proteins showed loss of expression of at least one protein in 1/18 EO-CRC patients and 22/179 of older patients (p=0.728).
From the EO-CRC patients, 16 were evaluated in the Familial Cancer Clinic and 14 underwent germline mutation analysis: 13 patients had inconclusive results, one of them presented a MUTYH heterozygote mutation and another was diagnosed with MUTYH-associated Polyposis (composed heterozygote mutation).

Conclusion

Colorectal cancer showed distinctive features in the younger population, with a higher prevalence of lymphovascular invasion and, possibly, a higher incidence of metastatic disease at diagnosis. Smoking had a significant association with CRC, especially in this younger population. Whether this means there is a biological difference is not yet clear. More evidence is needed in order to clarify EO-CRC aetiology and to develop screening and improve management strategies.

References

Siegel RL, Jakubowski CD, Fedewa SA, Davis A, Azad NS. Colorectal Cancer in the Young: Epidemiology, Prevention, Management. Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-14. doi: 10.1200/EDBK_279901. PMID: 32315236

Introduction

​The actual screening of colorectal cancer (CRC) includes people of 45 years old and patients with alcoholic liver cirrhosis (LC) have an elevated risk of developing colon cancer. Curative treatment of CRC in patients with an existing diagnosis of LC can be a challenge, requiring major surgical resection and may include liver-toxic chemotherapy. Postoperative morbidity and mortality are elevated in patients with LC. For improved survival, optimization of liver function is more important than adjuvant chemotherapy.

Aims & Methods

Our study included 149 hospitalized LC patients Classes Child- Pugh A, B and C, meanage 56 years old, during April 2023-March 2024, of which 13 cases presented lower bleeding, iron deficiency anemia, intestinal transit disorders, abdominal pain, and familial history of CRC. Clinical and paraclinical diagnostic of CRC in LC patients were made by digital rectal examination, hematological samples, rectosigmoidoscopy, total colonoscopy, abdominal ultrasound, computed tomography and magnetic resonance imaging.

Results

Biological tests indicated anemia, trombocitopenia, increased ESR, biochemical liver tests increased, occult bleeding (FIT), and the increase of the tumor markers CA19-9, AFP, CEA that is particularly useful for monitoring treated CRC. Flexible rectosigmoidoscopy detected six cases of rectal cancer, three cases of rectosigmoidian tumors, and total colonoscopy was the "gold standard" imaging investigation that detected two cases of descending colon cancer, one case of hepatic flexure tumor and one patient with ascending colon cancer. Of patients with LC Class Child Pugh A, 6 cases were operated by laparotomy, being referred to Oncology Institute with favorable outcomes, and the rest of seven patients with LC Class Child Pugh B and C had advanced CRC, being treated by chemotherapy. Abdominal ultrasound visualizes liver metastases, abdominal lymph nodes and CT, MRI were the main methods used for staging CRC before surgical and oncological treatment.

Conclusion

Colonoscopy is the exploration of choice in CRC detection with 97% sensitivity, providing histopathological examination by tumor biopsy and also diagnosis of synchronous cancer. Early diagnosis of CRC is essential to prevent complications and increase the survival rate in LC. Men with LC are predominantly affected of CRC. Abdominal ultrasound, CT or MRI are the main imaging investigations recommended in CRC staging before the surgical and oncological treatment. Laparotomy should be preferred in patients with LC. Survival rate is strongly associated with the improvements in liver function. Echoendoscopy, immunoscintigraphy with monoclonal antibodies can be useful in CRC and genetic testing of tumor DNA markers in stool can be recommended in families with genetic syndromes (Turcot, FAP).

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.