Colorectal Cancer In Germany Research Articles

Proportion and characteristics of screen-detected and non-screen-detected colo-rectal cancers in Germany.

Germany has a long-standing colorectal cancer (CRC) screening offer. We aimed to quantify and characterize screen-detected colorectal cancers (sdCRCs) in Germany. We conducted a cross-sectional study based on a healthcare database covering ~20% of the German population; we included CRC patients aged ≥ 55 years diagnosed in 2010-2018. Patients with a screening colonoscopy or a fecal occult blood test followed by colonoscopy within 180 days before diagnosis were classified as sdCRCs and compared to non-sdCRCs regarding age, stage and comorbidities. In 2018, 25% of male and 22% of female CRC patients were screen-detected. Regarding characteristics of all included CRC cases (N = 82,538), sdCRC patients were younger than non-sdCRCs (average difference men / women: 2.6 / 4.4 years). The proportion of advanced CRC among sdCRCs and non-sdCRCs, respectively, was 33 and 42% in women (men: 36 and 45%). Severe comorbidities were more prevalent in non-sdCRCs compared to sdCRCs (e.g. in male / female patients aged 65-74: 35% vs. 27% / 26% vs. 19%). Prevalences of hypertension and obesity were similar in both groups. Our study suggests that about one fourth of CRCs in Germany are screen-detected. Among patients with non-sdCRC, not only advanced stage but also severe comorbidity was more common than in sdCRCs.

Trends and outcomes in colorectal cancer surgery: a multicenter cross-sectional study of minimally invasive versus open techniques in Germany

BackgroundThe objective of this study was to assess the trend from open to modern minimally invasive (laparoscopic and robot-assisted) surgical techniques for colorectal cancer (CRC) in Germany, with a particular focus on hospital mortality, postoperative complications, and length of hospital stay.MethodsA multicenter cross-sectional study was conducted using data from 36 German hospitals, encompassing 1,250,029 cases from January 2019 to December 2023. The study included all hospitalized patients aged ≥ 18 with CRC who underwent surgery. Surgical cases were categorized as open or minimally invasive. Outcomes assessed included in-hospital mortality, morbidity, and hospital length of stay. Statistical analyses involved multivariable logistic and linear regression models adjusted for main diagnosis, metastasis presence, age, sex, and comorbidities.ResultsThe study included 4525 CRC cases: 2767 underwent open surgery and 1758 underwent minimally invasive surgery (173 robotic). In-hospital mortality was significantly higher in open surgery (6.1% vs. 1.7%). Open surgery was also significantly associated with higher rates of acute post-hemorrhagic anemia (OR: 2.38; 95% CI: 1.87–3.02), respiratory failure (OR: 1.71; 95% CI: 1.34–2.18), and intraoperative and postprocedural complications (OR: 3.64; 95% CI: 2.83–4.70). Average hospital stay was longer for open surgery (19.5 days vs. 11.0 days).ConclusionDespite the advantages of minimally invasive surgery, including reduced mortality, morbidity, and shorter hospital stays, open surgery remains the predominant approach for CRC in Germany. These findings underscore the need for increased adoption of minimally invasive techniques and highlight the potential benefits of shifting toward minimally invasive methods to enhance the overall quality of CRC care.Graphical abstract

Encorafenib plus cetuximab in patients with metastatic, BRAF V600E-mutated, colorectal carcinoma: First effectiveness data of the European multi-centric, multi-national, non-interventional study—BERING-CRC.

3551 Background: Targeted treatment with encorafenib plus cetuximab (E+C) represents the standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer after prior systemic therapy. The approval was based on the data from the BEACON CRC trial; updated data of the trial showed a median progression free survival (mPFS) of 4.3 months and a median overall survival (mOS) of 9.3 months for the treatment with E+C compared to a mPFS of 1.5 months and a mOS of 5.9 months with chemotherapy plus cetuximab (hazard ratio [HR], 0.61 [95% CI, 0.48 to 0.77]) and an objective response rate (ORR) of 20% compared to 2%. The tolerability profile was consistent with the known safety profile of each agent and was generally well tolerated. As data from controlled clinical trials are based on a selected patient population, the non-interventional study (NIS) BERING CRC investigates the use of E+C at real-world conditions in a broader patient population. Methods: BERING CRC is an ongoing multi-national, multi-centric, prospective, longitudinal NIS. It represents the first NIS to investigate the real-world use of E+C in BRAF V600E-mutant metastatic colorectal cancer in Germany, Austria and Switzerland. The study aims to enroll 300 patients (pts) from 124 sites, treated according to the label. The primary study objective is to assess the 1-year OS rate. Secondary endpoints include effectiveness outcomes, quality of life, safety and tolerability of the treatment. The influence of prognostic factors on efficacy, as well as safety and tolerability will also be assessed. Results: Here we present the first planned effectiveness analysis based on the initial 100 enrolled pts (95 treated / 95 evaluable; median observation time: 5.9 mo). This analysis set showed an older patient population compared to the BEACON trial with a median age of 67 yrs (BEACON: 61 yrs) and fewer ECOG PS 0 patients (0/1/2/3: BERING 36/50/8/2 % vs BEACON 51/47/2/0 %). 96% presented with distant metastases (liver: 54%), with an involvement of ≥3 organ systems in 14%. E+C was mainly administered after one prior systemic therapy (73%). ORR was 24%, mPFS 5.3 months and mOS 10.3 months. Treatment emergent adverse events (TEAE) were reported in 73% of pts (grade 3/4: 38%). Main TEAE (≥10%, all grades) were: rash (12%) and nausea (11%). Conclusions: This first effectiveness analysis of BERING CRC shows the use of E+C in a real-world population. Despite the older study population and less ECOG PS 0 patients as compared to the pivotal study, the observed treatment effectiveness and safety profile are consistent with data from the BEACON CRC study. The recruitment of this study is ongoing and future analysis of the study will include an additional analysis of subgroups, effectiveness and QoL. Clinical trial information: NCT04673955 .

Influence of Certification Program on Treatment Quality and Survival for Rectal Cancer Patients in Germany: Results of 13 Certified Centers in Collaboration with AN Institute.

The certification of oncological units as colorectal cancer centers (CrCCs) has been proposed to standardize oncological treatment and improve the outcomes for patients with colorectal cancer (CRC). The proportion of patients with CRC in Germany that are treated by a certified center is around 53%. Lately, the effect of certification on the treatment outcomes has been critically discussed. Our aim was to investigate the treatment outcomes in patients with rectal carcinoma at certified CrCCs, in German hospitals of different medical care levels. We performed a retrospective analysis of a prospective, multicentric database (AN Institute) of adult patients who underwent surgery for rectal carcinoma between 2002 and 2016. We included 563 patients from 13 hospitals of different medical care levels (basic, priority, and maximal care) over periods of 5 years before and after certification. The certified CrCCs showed a significant increase in the use of laparoscopic approach for rectal cancer surgery (5% vs. 55%, p < 0.001). However, we observed a significantly prolonged mean duration of surgery in certified CrCCs (161 Min. vs. 192 Min., p < 0.001). The overall morbidity did not improve (32% vs. 38%, p = 0.174), but the appearance of postoperative stool fistulas decreased significantly in certified CrCCs (2% vs. 0%, p = 0.036). Concerning the overall in-hospital mortality, we registered a positive trend in certified centers during the five-year period after the certification (5% vs. 3%, p = 0.190). The length of preoperative hospitalization (preop. LOS) was shortened significantly (4.71 vs. 4.13 days, p < 0.001), while the overall length of in-hospital stays was also shorter in certified CrCCs (20.32 vs. 19.54 days, p = 0.065). We registered a clear advantage in detailed, high-quality histopathological examinations regarding the N, L, V, and M.E.R.C.U.R.Y. statuses. In the performed subgroup analysis, a significantly longer overall survival after certification was registered for maximal medical care units (p = 0.029) and in patients with UICC stage IV disease (p = 0.041). In patients with UICC stage III disease, we registered a slightly non-significant improvement in the disease-free survival (UICC III: p = 0.050). The results of the present study indicate an improvement in terms of the treatment quality and outcomes in certified CrCCs, which is enforced by certification-specific aspects such as a more differentiated surgical approach, a lower rate of certain postoperative complications, and a multidisciplinary approach. Further prospective clinical trials are necessary to investigate the influence of certification in the treatment of CRC patients.

Effects of the Pandemic on the Care of Patients With Colorectal Cancer.

During the COVID-19 pandemic, there was a decrease in the rates of diagnosis and treatment of cancer. However, only a few detailed analyses have been made to date regarding the effect of the pandemic on the care of cancer patients in Germany. Such studies are needed as the basis for well-founded recommendations on health-care delivery priorities during pandemics and other, comparable situations of crisis. This review is based on publications that were retrieved by a selective search of the literature for controlled studies from Germany on the effects of the pandemic on colonoscopies, first diagnoses of colorectal cancer (CRC), surgical procedures for CRC, and CRC-related mortality. Compared to 2019, the rate of screening colonoscopies performed by physicians in private practice was 1.6% higher in 2020 and 4.3% higher in 2021. On the other hand, the rate of diagnostic colonoscopies in the inpatient setting was 15,7% lower in 2020, while that of therapeutic colonoscopies was 11.7% lower. According to the data evaluated here, first diagnoses of CRC were 2.1% less common in January to September in 2020 than they had been in 2019; according to routine data collected by the statutory health insurance provider GRK, surgery for CRC was 10% less common in 2020 than in 2019. With regard to mortality, sufficient data from Germany were lacking to draw definite conclusions. International modeling data suggest an increase in mortality due to decreased colorectal screening rates during the pandemic that may at least be partially compensated for by intensified screening strategies following the pandemic. Three years after the onset of the COVID-19 pandemic, there is still only a limited evidence base for an evaluation of the effects of the pandemic on medical care and on the outcomes of patients with CRC in Germany. The implementation of central data and research infrastructures will be necessary for further study of the long-term effects of this pandemic, as well as to enable optimal preparedness for future crisis situations.

Impact of Reducing Intake of Red and Processed Meat on Colorectal Cancer Incidence in Germany 2020 to 2050—A Simulation Study

According to the International Agency for Research on Cancer (IARC), there is sufficient evidence for the carcinogenicity of processed meat consumption in humans, specifically regarding colorectal cancer (CRC) risk. Evidence for the carcinogenicity of red meat consumption is more limited but points in the same direction. A macro-simulation approach was used to calculate age- and sex-specific potential impact fractions in a 30-year period (2020-2050). We estimated numbers and proportions of future CRC cases preventable under different scenarios of reducing the intake of processed and red meat in the German population. Eliminating processed meat intake could reduce the burden of CRC by approximately 205,000 cases in Germany (9.6%) in 2020-2050, 2/3 among males (145,000) and 1/3 among females (60,000). Without red meat intake, approximately 63,000 CRC cases could be avoided (2.9%), 39,000 among males and 24,000 among females. Reductions in the mean consumption of both processed and red meat by one or two servings (each 11 or 22 g) per day would be expected to reduce CRC case numbers by 68,000 (3.1%) and 140,000 (6.5%), respectively. A reduction in red and processed meat intake might substantially reduce the incidence of CRC in Germany. The means of achieving such a reduction might include price and taxation policies, food labeling, and clearer risk communication aiming to reduce individual intake.

Polyp detection rate and cumulative incidence of post-colonoscopy colorectal cancer in Germany.

Studies have shown that the quality of colonoscopy influences the incidence of post-colonoscopy colorectal cancer (PCCRC). However, data from Germany on this association are lacking. We aimed to assess cumulative incidence of PCCRC in persons undergoing colonoscopy in Germany according to the physician's polyp detection rate (PDR). Using the German Pharmacoepidemiological Research Database (GePaRD) with claims data of ~20% of the German population, we included persons with a baseline colonoscopy between 2008 and 2017 and categorized them according to the procedure at baseline (snare polypectomy, forceps polypectomy, no polypectomy). In each subgroup, we distinguished between persons examined by physicians with a PDR in the lowest quartile vs higher quartiles and described cumulative CRC incidence during follow-up. Overall, 822 715 persons examined by 1752 physicians were included. One quarter of the physicians had a PDR ≤21.8% (lowest quartile). In all subgroups, the 5-year cumulative CRC incidence was statistically significantly higher in persons examined by physicians with a PDR ≤21.8% vs >21.8%: It was 69% higher in persons with snare polypectomy (0.88% vs 0.52%), 87% higher in persons with forceps polypectomy (0.58% vs 0.31%), and 48% higher in persons without polypectomy at baseline (0.31% vs 0.21%). In conclusion, we found a substantially increased PCCRC risk in persons examined by physicians with a low PDR in Germany, irrespective of the baseline findings. Our study highlights the importance of a high-quality colonoscopy to maximize the preventive effect of colonoscopy on CRC incidence.

Aspirin, Risk of Colorectal Cancer, & Genetic Risk-Letter.

We read with interest the study by Bakshi and colleagues in which they explored the association between genetic susceptibility to colorectal cancer and aspirin, using a 95-variant colorectal cancer polygenic risk score (PRS) in the participants of ASPREE (ASPirin in Reducing Events in the Elderly) trial (1). The ASPREE trial was a prospective double-blinded, placebo-controlled randomized trial in which 12,609 individuals of European descent ages ≥70 years were enrolled. They concluded that the 95-SNP PRS continues to identify individuals at higher risk of colorectal cancer, including individuals with no family history of colorectal cancer. Recently, Chen and colleagues, using data collected from a large population-based case–control study on colorectal cancer in Germany, analyzed PRS based on 140 colorectal cancer–related risk loci to quantify the genetic risk, reported that regular use of NSAIDs, including aspirin, was associated with significantly reduced colorectal cancer risk regardless of individual genetic profile (2). However, randomization of aspirin treatment in the ASPREE trial was not associated with a reduced incidence of colorectal cancer (P = 0.7).Also, a pooled analysis of two large U.S. cohort studies was published, the Nurses’ Health Study and Health Professionals Follow-up Study, with a total of 94,540 participants ages ≥70 years old (3). The analysis showed that initiating aspirin at an older age was not associated with a lower risk of colorectal cancer. In contrast, those who used aspirin before age 70 years and continued into their 70s or later had a reduced risk of colorectal cancer. A possible explanation is that a beneficial effect of aspirin for colorectal cancer requires at least 5 to 10 years of use (3).Over the last decades, aspirin has been an extensively prescribed drug with antiplatelet and anti-inflammatory effects (4). The mechanism of aspirin's possible anticancer effect is under investigation, but it is believed that it is through inhibiting catalytic enzymes COX-1 and COX-2 involved in prostaglandin synthesis. Therefore, in subjects taking aspirin, gut microbiome composition will shift toward a lower proportion of proinflammatory, colorectal cancer–predisposing bacteria (e.g., Fusobacteria) and a higher proportion of anti-inflammatory, colorectal cancer–protective bacteria (e.g., butyrate-producing bacteria; ref. 5).The recent study by Bakshi and colleagues and other recent high impacted trials on the effect of aspirin on cardiovascular disease and colorectal cancer risks have high translational values into the daily practice. However, there is a need for future preclinical and clinical trials on the impact of aspirin on gut microbiota and their metabolic and immunoregulatory potential.See the Response, p. 703No disclosures were reported.

Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study.

Colorectal cancer incidence increases with patient age. The aim of this study was to assess, at the nationwide level, in-hospital mortality, and failure to rescue in geriatric patients (≥ 80 years old) with colorectal cancer arising from postoperative complications. All patients receiving surgery for colorectal cancer in Germany between 2012 and 2018 were identified in a nationwide database. Association between age and in-hospital mortality following surgery and failure to rescue, defined as death after complication, were determined in univariate and multivariate analyses. Three lakh twenty-eight thousands two hundred and ninety patients with colorectal cancer were included of whom 77,287 were 80 years or older. With increasing age, a significant relative increase in right hemicolectomy was observed. In general, these patients had more comorbid conditions and higher frailty. In-hospital mortality following colorectal cancer surgery was 4.9% but geriatric patients displayed a significantly higher postoperative in-hospital mortality of 10.6%. The overall postoperative complication rate as well as failure to rescue increased with age. In contrast, surgical site infection (SSI) and anastomotic leakage (AL) did not increase in geriatric patients, whereas the associated mortality increased disproportionately (13.3% for SSI and 29.9% mortality for patients with AI, both p < 0.001). Logistic regression analysis adjusting for confounders showed that geriatric patients had almost five-times higher odds for death after surgery than the baseline age group below 60 (OR 4.86; 95%CI [4.45-5.53], p < 0.001). Geriatric patients have higher mortality after colorectal cancer surgery. This may be partly due to higher frailty and disproportionately higher rates of failure to rescue arising from postoperative complications.

The CIRCULATE Trial: Circulating Tumor DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation (AIO-KRK-0217)

BackgroundGuidance regarding adjuvant treatment decisions in stage II colorectal cancer (CRC) remains uncertain due to lack of predictive clinical or molecular markers. Recently, postoperative circulating tumour (ct)DNA has been demonstrated to be a strong prognostic marker in early colon cancer. Patients and MethodsCIRCULATE enrols patients with stage II microsatellite stable CRC in Germany (AIO) and Austria (ABCSG). Within the AIO, screening is supported by ColoPredict Plus 2.0, a molecular registry, and screening platform for interventional trials.Patient-specific mutations are centrally analysed by next generation sequencing in the resected primary tumour. A postoperative plasma sample is subsequently screened for the specific mutation(s).ctDNA positive (ctDNApos) patients are randomised (2:1) chemotherapy (capecitabine, oxaliplatin added an investigator's choice) or to follow-up (control group).ctDNA negative (ctDNAneg) patients are randomised (1:4) to be followed-up within CIRCULATE (control group) or outside the trial. Patients in the control group remain blinded to the ctDNA results.The primary objective is to compare disease free survival (DFS) of ctDNApos patients with chemotherapy or control. To demonstrate a treatment effect with a hazard ratio of 0.617 (3-year DFS rates 42.5% vs. 25%), 231 ctDNApos and estimated 2079 ctDNAneg patients are randomised.Secondary aims include to compare overall survival and DFS in the ctDNApos and ctDNAneg patient cohorts and ctDNA kinetics. ConclusionThe CIRCULATE trial may establish ctDNA for adjuvant treatment decision in stage II colon cancer – and with the secondary objectives – support a ctDNA guided follow up in colon cancer stage II and beyond.

Non-steroidal anti-inflammatory drugs, polygenic risk score and colorectal cancer risk.

The regular use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk. To explore whether this association varies according to background polygenic risk for CRC. Data were collected from a large population-based case-control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC-related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the 'genetic risk equivalent' (GRE), a recently developed metric for effective risk communication. In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74], as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P=0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE -32, 95% CI -41, -22). The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score.

Incidence and Mortality of Proximal and Distal Colorectal Cancer in Germany—Trends in the Era of Screening Colonoscopy.

The use of colonoscopy has increased and colorectal cancer (CRC) incidence has decreased after the introduction of screening colonoscopy in Germany. However, it remains unknown to what extent progress has been achieved in the prevention of cancer in the proximal colon, distal colon, and rectum. We analyzed trends in CRC incidence (2000-2016) and mortality (2000-2018) in Germany by sex, age, and tumor location. The age-standardized incidence of CRC declined by 22.4% (from 65.3 to 50.7 per 100 000) in men and by 25.5% (from 42.7 to 31.8 per 100 000) in women. CRC mortality declined by 35.8% (from 29.6 to 19.0 per 100 000) in men and by 40.5% (19.0 to 11.3 per 100 000) in women. Despite demographic changes, the annual numbers of CRC cases and deaths still decreased from about 60 400 to 58 300 and from around 28 700 to 24 200, respectively. The decline in incidence was greatest in groups aged ≥ 55 years. While the incidence of cancer in the distal colon and rectum decreased by 34.5% and 26.2%, respectively, in men and by 41.0% and 27.9% in women, the incidence of proximal colon cancer remained stable in men and decreased by only 7.0% in women. However, a major shift towards earlier stages was observed for the proximal cancers. The results support the assumption that the increased use of colo - noscopy has contributed to substantial reductions in the incidence of distal CRC incidence and the mortality from cancers in the entire colon and rectum.

Uptake Rates of Novel Therapies and Survival Among Privately Insured Versus Publicly Insured Patients With Colorectal Cancer in Germany

Background: In the era of personalized medicine, cancer care is subject to major changes and innovations. It is unclear, however, to what extent implementation of such innovations and their impact on patient outcomes differ by health insurance type. This study compared provision of treatment and survival outcomes among patients with colorectal cancer (CRC) who had statutory health insurance (SHI) versus private health insurance (PHI) in Germany. Methods: We analyzed patterns of CRC treatment (surgery, chemotherapy/radiotherapy, and targeted therapy) and survival in a large cohort of patients who were diagnosed with CRC in 2003 through 2014 and were observed for an average of 6 years. Associations of type of health insurance with treatment administration and with overall, CRC-specific, and recurrence-free survival were investigated using multivariable logistic and Cox proportional hazards models, respectively. Results: Of 3,977 patients with CRC, 427 (11%) had PHI. Although type of health insurance was not associated with treatment administration in patients with stage I–III disease, those with stage IV disease with PHI more often received targeted therapy (65% vs 40%; odds ratio, 2.43; 95% CI, 1.20–4.91), with differences decreasing over time because of catch-up of uptake rates in patients with SHI. Median overall survival was longer in patients with PHI than in those with SHI (137.0 vs 114.9 months; P=.010), but survival advantages were explained to a large extent by differences in sociodemographic factors. In patients with stage IV disease, survival advantages of PHI were nonsignificant and were restricted to the early years after diagnosis. Conclusions: We observed major differences in uptake of targeted therapy between patients with PHI and those with SHI but no differences in patient survival after adjusting for relevant sociodemographic, clinical, and tumor characteristics. Further studies are needed on factors associated with the uptake of therapeutic innovations and their impact on patient survival by health insurance type.

Learning-by-doing: the importance of experiential knowledge sharing for meeting the information needs of people with colorectal cancer in Germany—a qualitative study

ObjectiveThe aim of this article is to understand how, when and why the topics of information and information needs arise when people diagnosed with colorectal cancer (CRC) narrate their illness...

457P 1st-line panitumumab plus FOLFIRI or FOLFOX for patients with RAS wildtype metastatic colorectal cancer in Germany: Interim results of the non-interventional study VALIDATE

The metastatic colorectal cancer (mCRC) prognostic score (mCCS) predicts overall survival (OS) of patients (pts) with mCRC at start of 1st-line therapy (Marschner N, et al. Colorectal Dis. 2019). Based on 5 clinical routine parameters, i.e. tumor stage, tumor grading and lymph node (LN) ratio (affected LNs / total number of resected LNs) at primary diagnosis, primary tumor resectability and number of metastatic sites at start of 1st-line treatment, pts were assigned to three prognostic risk groups with decreasing OS from low to intermediate and high risk group.

Age-specific sequence of colorectal cancer screening options in Germany: A model-based critical evaluation

BackgroundThe current organized screening program for colorectal cancer in Germany offers both sexes 5 annual fecal immunochemical tests (FITs) between ages 50 and 54 years, followed by a first screening colonoscopy at age 55 years if all of these FITs were negative. We sought to assess the implications of this approach for key parameters of diagnostic performance.Methods and findingsUsing a multistate Markov model, we estimated the expected detection rates of advanced neoplasms (advanced adenomas and cancers) and number needed to scope (NNS) to detect 1 advanced neoplasm at a first screening colonoscopy conducted at age 55 after 5 preceding negative FITs and compared them with the corresponding estimates for a first screening colonoscopy at age 55 with no preceding FIT testing. In individuals with 5 consecutive negative FITs undergoing screening colonoscopy at age 55, expected colonoscopy detection rate (NNS) was 3.7% (27) and 0.10% (1,021) for any advanced neoplasm and cancer, respectively, in men, and 2.1% (47) and 0.05% (1,880) for any advanced neoplasm and cancer, respectively, in women. These NNS values for detecting 1 advanced neoplasm are approximately 3-fold higher, and the NNS values for detecting 1 cancer are approximately 8-fold higher, than those for a first screening colonoscopy at age 55 without prior FITs. This study is limited by model simplifying assumptions and uncertainties related to input parameters.ConclusionsScreening colonoscopy at age 55 after 5 consecutive negative FITs at ages 50–54, as currently offered in the German cancer early detection program, is expected to have very low positive predictive value. Our results may inform efforts to enhance the design of screening programs.

Cost-effectiveness of FOLFIRI + cetuximab vs FOLFIRI + bevacizumab in the first-line treatment of RAS wild-type metastatic colorectal cancer in Germany: data from the FIRE-3 (AIO KRK-0306) study

Aims: This analysis evaluates the cost-effectiveness of first-line treatment with FOLFIRI + cetuximab vs FOLFIRI + bevacizumab for patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in Germany based on the randomized phase 3 FIRE-3 trial. For patients with RAS wt mCRC, FOLFIRI + cetuximab yielded statistically significant median overall survival gains over FOLFIRI + bevacizumab.Materials and methods: A standard 3-state partitioned survival cost-utility model was developed to compare the health benefits and costs of treatment from a German social health insurance perspective using individual patient–level trial data. Health outcomes were reported in life-years (LYs) and quality-adjusted life-years (QALYs) gained. Survival was estimated based on Kaplan-Meier (KM) curves supplemented with best-fitting parametric survival model extrapolations. Subgroup analyses of patients with a left-sided primary tumor location or patients with metastases confined to the liver were performed.Results: In the modified intention-to-treat analysis, FOLFIRI + cetuximab, providing 0.68 additional LYs (0.53 QALYs), yielded incremental cost-effectiveness ratios (ICERs) of €36,360/LY and €47,250/QALY. In subgroup analyses, patients experienced improved survival gains without a corresponding increase in costs, resulting in lower ICERs. Our model was most sensitive to changes in treatment duration across all lines of therapy, utility of progressive disease, as well as patients’ weight and body surface area.Limitations: This cost-effectiveness analysis was based on patient-level data from the FIRE-3 trial. Trial outcomes may not adequately reflect those in the real-world setting. Additionally, resource use and costs were obtained from tariff lists, which do not account for differences in treatment practice. These considerations limit generalizability of outcomes to other countries, or within the German healthcare setting.Conclusions: Based on our analyses, FOLFIRI + cetuximab is cost-effective compared with FOLFIRI + bevacizumab in patients with RAS wt mCRC, with ICERs well below willingness-to-pay thresholds for diseases with a high burden.

Incidence of advanced colorectal cancer in Germany: comparing claims data and cancer registry data

BackgroundIncidence rates of advanced cancer stages are important, e.g., for monitoring cancer screening programs. However, information from cancer registries on tumor stage is often incomplete. Exemplified by colorectal cancer (CRC), we explored the potential of German claims data to estimate incidence rates of advanced cancer stages.MethodsWe used claims data of the German Pharmacoepidemiological Research Database (GePaRD; information on > 20 million persons) to identify incident patients with advanced CRC based on ICD-10 codes for CRC and secondary malignant neoplasms. We calculated annual age-standardized incidence rates (ASIRs) of advanced CRC per 100,000 for the years 2008–2015 stratified by the presence of affected lymph nodes only (C77) vs. distant metastases (C78-C79) and compared them to ASIRs determined using data (2008–2014) from the German Centre for Cancer Registry Data (ZfKD).ResultsIn GePaRD, the ASIRs of advanced CRC per 100,000 in 2014 were 21.5 among men and 14.9 among women. Compared to ZfKD data the ASIR in GePaRD was 2.58 lower in men and 0.27 higher in women (per 100,000) in 2014. Stratification by presence of distant metastases showed divergent patterns: the ASIRs regarding distant metastases were ~ 50% (women) and ~ 30% (men) higher, and the ASIRs regarding affected lymph nodes only were ~ 40% lower in GePaRD as compared to ZfKD.ConclusionWhile ASIRs of advanced CRCs overall agreed well between claims and cancer registry data in 2014, the analyses stratified by presence of distant metastases showed differences. Cancer registries might underestimate ASIRs of CRCs with distant metastases.

&lt;p&gt;Decentralized colorectal cancer care in Germany over the last decade is associated with high in-hospital morbidity and mortality&lt;/p&gt;

PurposeDespite several national initiatives, centralization of cancer care in Germany remains insufficient for most malignancies. Currently, there is a plethora of centers, including 290 voluntary certified and audited colorectal cancer (CRC) centers by the end of 2017, in the nation with many patients still being treated outside of such centers. This study aimed to assess morbidity and mortality rates of surgical procedures for primary colorectal CRC in Germany over the last decade through a comprehensive unbiased analysis.Patients and methodsWe performed an analysis of the national diagnosis-related group inpatient statistics from 2005 to 2015 including all German hospitals. All patients who underwent surgeries for primary CRC during the study period were included.ResultsA total of 351,028 cases were analyzed (61.6% colonic and 38.4% rectal resections). The mortality rate of colonic resections remained high during the study period (4.9% in 2005 vs 4.5% in 2015; P=0.57). Reduced perioperative mortality after rectal surgery was observed only after 2012 compared to previous years (3.8% in 2005 vs 3.0% in 2015; P<0.001), with no further improvement. In-hospital morbidity such as anastomotic leak, wound infections, hemorrhage, pneumonia, deep vein thrombosis, and lung embolism did not improve for either rectal or for colonic surgery, but in contrast, most outcomes deteriorated over time.ConclusionThe present study challenges the current national health policies aiming to improve outcomes of surgical patients. CRC care in Germany remains decentralized with high in-hospital morbidity and mortality rates. New national strategies focusing on the implementation of centralization and high-quality CRC care are urgently needed.

Activated ATF6 Induces Intestinal Dysbiosis and Innate Immune Response to Promote Colorectal Tumorigenesis

Activating transcription factor 6 (ATF6) regulates endoplasmic reticulum stress. We studied whether ATF6 contributes to the development of colorectal cancer (CRC) using tissue from patients and transgenic mice. We analyzed data from 541 patients with CRC in The Cancer Genome Atlas database for genetic variants and aberrant expression levels of unfolded protein response genes. Findings were validated in a cohort of 83 patients with CRC in Germany. We generated mice with intestinal epithelial cell-specific expression of the active form of Atf6 (nATF6IEC) from 2 alleles (homozygous), mice with expression of nATF6IEC from 1 allele (heterozygous), and nATF6IECfl/fl mice (controls). All nATF6IEC mice were housed under either specific-pathogen-free or germ-free conditions. Cecal microbiota from homozygous nATF6IEC mice or control mice was transferred into homozygous nATF6IEC mice or control mice. nATF6IEC mice were crossed with mice with disruptions in the myeloid differentiation primary response gene 88 and toll-like receptor adaptor molecule 1 gene (Myd88/Trif-knockout mice). Intestinal tissues were collected from mice and analyzed by histology, immunohistochemistry, immunoblots, gene expression profiling of unfolded protein response and inflammatory genes, array-based comparative genome hybridization, and 16S ribosomal RNA gene sequencing. Increased expression of ATF6 was associated with reduced disease-free survival times of patients with CRC. Homozygous nATF6IEC mice developed spontaneous colon adenomas at 12 weeks of age. Compared with controls, homozygous nATF6IEC mice had changes in the profile of their cecal microbiota, increased proliferation of intestinal epithelial cells, and loss of the mucus barrier-all preceding tumor formation. These mice had increased penetration of bacteria into the inner mucus layer and activation of signal transducer and activator of transcription 3, yet inflammation was not observed at the pretumor or tumor stages. Administration of antibiotics to homozygous nATF6IEC mice greatly reduced tumor incidence, and germ-free housing completely prevented tumorigenesis. Analysis of nATF6IEC MyD88/TRIF-knockout mice showed that tumor initiation and growth required MyD88/TRIF-dependent activation of signal transducer and activator of transcription 3. Transplantation of cecal microbiota from nATF6IEC mice and control mice, collected before tumor formation, caused tumor formation in ex-germ-free nATF6IEC mice. In patients with CRC, ATF6 was associated with reduced time of disease-free survival. In studies of nATF6IEC mice, we found sustained intestinal activation of ATF6 in the colon to promote dysbiosis and microbiota-dependent tumorigenesis.