Survival in patients with colorectal cancer diagnosed by screening colonoscopy

doi:10.1016/j.gie.2014.12.048

Gastrointestinal Endoscopy

Volume 82, Issue 1, July 2015, Pages 133-137

https://doi.org/10.1016/j.gie.2014.12.048 Get rights and content

Background

In Germany, screening colonoscopy was first established in 2002 as part of the national cancer screening program.

Objective

To evaluate whether colorectal cancer (CRC) survival differs when CRC is diagnosed by screening colonoscopy (S-CRC) versus diagnostic colonoscopy (D-CRC).

Design

Long-term, retrospective, multicenter, observational study.

Setting

Study centers: 10 private gastroenterology practices in Germany.

Patients

A total of 60 patients diagnosed with CRC during screening colonoscopy and 252 patients during diagnostic colonoscopy in 2002, 2003, and 2004.

Interventions

Colonoscopy.

Main Outcome Measurements

Survival of patients up to December 2013.

Results

Mean (± standard deviation [SD]) follow-up time was 81.0 (± 40.1) months. Union Internationale Contre le Cancer (UICC) stages I and II were found more often in S-CRC (81.6%) compared with D-CRC (59.9%; P < .002). Kaplan-Meier analysis showed significantly reduced overall survival for patients with D-CRC (mean [± SD] 86.9 [± 3.0] months; 95% confidence interval [CI], 81.0-92.8) compared with S-CRC (mean [± SD] 107.1 [± 4.9] months; 95% CI, 97.4-116.9; P = .003). When deaths not related to CRC were excluded, survival was still shorter for D-CRC patients (mean [± SD] 89.4 [± 3.0] months; 95% CI, 83.5-95.4) compared with S-CRC (mean [± SD] 109.6 [± 4.7] months; 95% CI, 100.2-119.0; P = .004).

Limitations

Retrospective study design.

Conclusion

In this long-term, retrospective study, patients with CRC diagnosed during screening colonoscopy lived significantly longer when compared with patients with CRC diagnosed during diagnostic colonoscopy.

Section snippets

Methods

This was a retrospective, multicenter, observational study investigating the influence of screening colonoscopy on survival of patients with CRC. Patients diagnosed with CRC in 2003, 2004, or 2005 were classified, based on indication for the examination (screening vs diagnostic colonoscopy) and followed until 2013. According to the 2002 German CRC guideline, patients aged ≥55 years can choose between 2 CRC screening methods: screening colonoscopy or FOBT. Patients with positive FOBT results

Study setting

All 10 private gastroenterology practices agreed to participate. A total of 372 patients were diagnosed with CRC in the years 2003, 2004, or 2005 at the 10 practices. Follow-up was complete in 312 patients; these patients were the cohort for further analysis, based on the study protocol. Reasons for loss of follow-up were inability to contact (n = 34), withdrawal of consent (n = 7), and incomplete data collection (n = 19). Mean (± SD) follow-up time was 81.0 (± 40.1) months.

Patient cohort

A total of 125 of

Discussion

Screening colonoscopy was established in Germany in 2002 as part of the national cancer screening program. Screening colonoscopy is associated with a stage-shift of CRC toward UICC stages I and II, suggesting that screening colonoscopy might improve survival of CRC patients.⁵ The aim of the present study was to investigate this hypothesis a decade after the introduction of the screening colonoscopy program in Germany.

The detection of early stage CRC previously has been associated with reduced

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Citation Excerpt :
Therefore, a stage shift by CRC colonoscopy screening is assumed. While this manuscript was under preparation another study appeared that showed that screening colonoscopy detected significantly more CRCs in early stages compared with diagnostic colonoscopy.28 Furthermore, patients with screen-detected CRCs lived longer than patients with CRCs diagnosed via diagnostic colonoscopies.
Screening for colorectal cancer (CRC) using fecal occult blood tests (FOBT) is associated with reduced CRC incidence and mortality. Population-based FOBT screening has led to identification of CRCs at earlier stages and longer patient survival times. We investigated the stage distribution of CRCs detected by colonoscopy in a large outpatient cohort.
We performed a retrospective analysis of colonoscopies performed on 524,954 outpatients (age, ≥55 y) in Germany from January 2006 through December 2009. Patients with chronic inflammatory bowel diseases, and those with a personal history of adenoma or CRC, were excluded. Colonoscopy findings were categorized on the basis of the most advanced lesion found; histologic samples were obtained from all patients with suspected cancer and analyzed. Cancers were staged based on Union Internationale Contre le Cancer criteria. We analyzed absolute and relative frequencies of CRCs identified and tumor stages for patients who underwent colonoscopy for screening, evaluation of a positive FOBT, and evaluation of symptoms.
Of the 6065 CRCs identified, 1750 were found in the screening group, 1075 in subjects with positive FOBT, and 3240 in patients with symptoms. Stage I CRC was detected more frequently in subjects who received screening colonoscopies (41.15%) or in those with positive FOBT (39.10%), than in individuals with symptoms (24.42%; P < .001). In contrast, the detection rates of stage IV CRC were 10.67%, 10.76%, and 18.64%, respectively (P < .001). We observed a shift toward lower T stages in the screening and FOBT work-up groups compared with the group with symptoms. Compared with subjects with symptoms, the odds of diagnosing CRC at an advanced stage were significantly lower in the screening group (odds ratio, 0.533; 95% confidence interval, 0.451–0.631) and the FOBT work-up group (odds ratio, 0.570; 95% confidence interval, 0.469–0.694).
In this large population-based study, CRC detected by colonoscopies performed for screening and evaluation of positive FOBTs had a lower stage than those diagnosed by colonoscopies in symptomatic patients. These findings support the value of screening colonoscopy to reduce the burden of CRC.
Investigating intra-tumor heterogeneity and expression gradients of miR-21, miR-92a and miR-200c and their potential of predicting lymph node metastases in early colorectal cancer
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Citation Excerpt :
National screening programs are initiated with the overall goal to increase the proportion of early detected CRCs and initiation of early treatment and improvement of CRC survival. Furthermore the removal of precancerous lesions with varying degrees of neoplasia is expected to decrease the incidence of CRC (Gill et al., 2012; Friedrich et al., 2015). Identification of CRC at an early stage leads to a new challenge with regard to assessment of metastatic potential, planning of follow-up and determination of individualized treatment of patients with early CRC where subsequent surgical treatment might be indicated.
miR-21, miR-92a and miR-200c are regulators of pathways involved in migration, intravasation and metastasis, and their tumor expression levels have been proposed as potential prognostic markers in colorectal cancer (CRC). In two parallel cohorts we examine intra-tumor expression levels in early stage CRC tissue in order to determine intra-tumor heterogeneity, potential systematic intra-tumor expression gradients of the miRNAs and to investigate the association to metastatic disease in early stage CRC.
Two parallel studies on archived formalin-fixed paraffin-embedded (FFPE) CRC tissue. Intra-tumor and inter-patient variances were analyzed in 9 early metastatic CRCs by measuring expression levels by qRT-PCR on isolated tissue samples from luminal, central and invasive border zones. Associations between miRNA expression levels and early metastasizing tumors was investigated in FFPE tissue from invasive border and central tumor zones from 47 early metastatic CRCs matched with 47 non-metastatic CRCs. Intra-tumor expression gradients were analyzed on both cohorts.
Mean intra-tumor coefficient of variation in the heterogeneity cohort was 38.5% (range: 33.1–49.0%) only slightly less than variation between patients (45.1%, range 37.0–49.5%). We demonstrated systematic expression gradients between tumor zones equal to a 3.23 (p = 0.003) and 1.36 (p = 0.014) fold lower expression in invasive areas for miR-200c, 1.52 (p < 0.001) and 1.27 (p = 0.021) fold lower expression in invasive areas for miR-92a. For miR-21 we found a 1.75 (p < 0.001) and 1.21 (p = 0.064) fold higher expression in invasive areas compared to luminal and central zones, respectively. No significant difference in expression levels between metastatic and non-metastatic tumors was demonstrated, nor a difference in intra-tumor gradients between metastatic and non-metastatic tumors.
This study provides evidence for moderate intra-tumor and inter-patient heterogeneities of three well-described potential prognostic markers in CRC. We demonstrate intra-tumor expression gradients indicating a differentiated expression of the target miRNAs between functional tumor zones, but the potential role as markers of early metastatic disease is still not fully clarified.
Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer
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Citation Excerpt :
Five year overall survival for 4317 Danish CRC patients who underwent surgery with curative intent was 75.5% for patients with localized disease (UICC stage I and II), 61.3% for patients with regional nodal spread and only 12.9% for patients with distant metastases (Danish Colorectal Cancer Group, 2014). National CRC screening programs increase the proportion of early detected CRCs and early treatment of CRC, and the removal of precancerous lesions with various degrees of neoplasia is expected to decrease CRC incidence and improve CRC survival (Gill et al., 2012,Friedrich et al., 2015). Screening also leads to a new challenge with regard to identification of possible invasive growth, metastatic potential, planning of follow-up and determination of individualized treatment of patients with early CRC where subsequent surgical treatment might be indicated.
Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial.
The study aim was to estimate the intra-tumor variance of three selected miRNAs: miR-92a, miR-375 and miR-424 in CRC tissue.
A retrospective study on archived formalin-fixed paraffin embedded tissue from 9 patients with CRC. miRNA tissue expression levels were analyzed by qRT-PCR on tissue representing luminal, central and invasive border zones. Variance components were estimated based on ∆∆Cp values using mixed modeling and presented as coefficients of variation (CV).
Intra-tumor variance was approximately half of the variance observed between patients with a mean intra-tumor CV of 56.4% (range 33.1–77.1%) and a mean inter-patient CV of 101.7% (range 48.8–152.7%). Furthermore we found a significant systematic difference in expression levels between tumor zones for miR-92a and miR-375 with a luminal-invasive difference equal to 0.60 Cp (95% CI: 0.30–0.89, p = 0.0003) for miR-92a and a luminal-invasive difference equal to 0.78 Cp (95% CI: 0.10–1.46, p = 0.027) for miR-375. Conclusion
While the intra-tumor variance of miR-92a, miR-375 and miR-424 is substantial, it only constitutes approximately 30% of the total variation. Functional deregulation between tumor zones might contribute to variations in measured expression levels, and thus knowledge of specific intra-tumor expression patterns is crucial in tissue sampling for research as well as in future diagnostics.
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: DISCLOSURE: All authors disclosed no financial relationships relevant to this article.

: If you would like to chat with an author of this article, you may contact Dr Friedrich at [email protected].

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Original articleClinical endoscopySurvival in patients with colorectal cancer diagnosed by screening colonoscopy

Background

Objective

Design

Setting

Patients

Interventions

Main Outcome Measurements

Results

Limitations

Conclusion

Section snippets

Methods

Study setting

Patient cohort

Discussion

Gastrointest Endosc

Lancet

Lancet

Gastroenterology

Lancet

Gastrointest Endosc

Gastrointest Endosc

Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths

N Engl J Med

Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies

BMJ

Original article
Clinical endoscopy
Survival in patients with colorectal cancer diagnosed by screening colonoscopy