Glycemic Control for Colorectal Cancer Survivors Compared to Those without Cancer in the Dutch Primary Care for Type 2 Diabetes: A Prospective Cohort Study.

Cancer survivors with diabetes tend to have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. We aimed to investigate whether glycemic control differs between colorectal cancer (CRC) survivors and those without cancer, among patients with type 2 diabetes being treated in the Dutch primary care. The Zwolle Outpatient Diabetes project Integrating Available Care database was linked with the Dutch Cancer Registry (n = 71,648, 1998-2014). The cases were those with stage 0-III CRC, and the controls were those without cancer history. The primary and secondary outcomes were the probability of reaching the glycated hemoglobin (HbA1c) target and the mean of HbA1c during follow-up, respectively. Mixed linear modeling was applied, where the status of CRC was a time-varying variable. Among the 57,330 patients included, 705 developed CRC during follow-up. The mean probability of reaching the HbA1c target during follow-up was 73% versus 74% (p = 0.157) for CRC survivors versus those without cancer, respectively. The mean HbA1c was 51.1 versus 50.8 mmol/mol (p = 0.045) among CRC survivors versus those without cancer, respectively. We observed a clinically comparable glycemic control among the CRC survivors without cancer, indicating that glycemic control for CRC survivors can be delegated to primary care professionals.

A population-based study on the prognostic impact of primary tumor sidedness in patients with peritoneal metastases from colon cancer.

Primary tumor location is an established prognostic factor in patients with (metastatic) colon cancer. Colon tumors can be divided into left-sided and right-sided tumors. The aim of this study was to determine the impact of primary tumor location on treatment and overall survival (OS) in patients with peritoneal metastases (PM) from colon cancer. This study is a retrospective, population-based cohort study. Records of patients diagnosed with colon cancer and synchronous PM, from 1995 through 2016, were retrieved from the Netherlands Cancer Registry (NCR). Data on diagnosis, staging, and treatment were extracted from the medical records by specifically trained NCR personnel. Information on survival status was updated annually using a computerized link with the national civil registry. In total, 7930 patients were included in this study; 4555 (57.4%) had a right-sided and 3375 (42.6%) had a left-sided primary tumor. In multivariable analysis right-sided primary tumor was associated with worse OS (HR: 1.11, 95% CI 1.03-1.19, P = .007). Of all patients diagnosed with PM, 564 (7.1%) underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Patients with left-sided primary tumors were more often candidates for CRS-HIPEC (6.5% vs. 8.0%, P = .008). OS of patients with right- and left-sided tumors who underwent CRS-HIPEC did not significantly differ. In conclusion, primary right-sided colon cancer was an independent prognostic factor for decreased OS in patients diagnosed with synchronous PM. In patients treated with CRS-HIPEC location of the primary tumor did not influence survival.

Nationwide analysis of hospital variation in preoperative radiotherapy use for rectal cancer following guideline revision.

INTRODUCTION: The revised Dutch colorectal cancer guideline (2014), led to an overall decrease in preoperative radiotherapy (RT) use. This study evaluates hospital variation in RT use for resectable rectal cancer and the influence of guideline revision, including the nationwide impact of changing RT application on short term outcomes. METHODS: Data of surgically resected rectal cancer patients registered in the Dutch ColoRectal Audit were extracted between 2011 and 2017. Patients were divided into groups based on time of guideline revision (<2014 and ≥ 2014). Primary outcome was guideline adherence at hospital level regarding RT application, stratified for three stage groups. Secondary outcomes included positive circumferential resection (CRM+) and 30-day complicated postoperative course. RESULTS: The groups consisted of 7364 and 12,057 patients, respectively. In total, 6772 patients did not receive RT (17.6% (<2014) vs. 45.7% (≥2014), p < 0.001). The largest increase of surgery alone was observed for cT1-2N0 stage rectal cancer (35.1% vs. 91.8%, p < 0.001), with a substantial decrease in hospital variation (IQR 22.2-50.0% vs. IQR 87.6-98.0%). For cT1-3N1MRF- stage rectal cancer, a substantial amount of hospital variation in short course RT remained after guideline revision (IQR 26.8-54.1% vs. IQR 26.2-50.0%). A significant decrease in CRM+ (5.8% vs. 4.2%, p < 0.001) and complicated course (22.5% vs. 18.5%, p < 0.001) was observed. CONCLUSIONS: Radiotherapy for early-stage rectal cancer was uniformly abandoned after guideline revision, while substantial hospital variation remained for intermediate risk resectable rectal cancer in the Netherlands. The substantial nationwide decrease in the use of RT for rectal cancer treatment did not negatively impact CRM involvement.

Years of Life Lost for Older Patients After Colorectal Cancer Diagnosis.

BACKGROUND: An aging population combined with an increased colorectal cancer (CRC) incidence in the older population will increase its prevalence in the elderly, questioning how many years of life are lost (YLLs) in these patients. PATIENTS AND METHODS: Data from 32,568 Dutch CRC patients ≥ 80 years were used to estimate the number of YLLs after diagnosis, using a reference age-, sex- and year-of-onset-matched cohort derived from national life tables. YLLs were additionally adjusted by comorbidities. Number needed to treat (NNT) was used as measure of surgical effect size. RESULTS: Surgery was applied in 74.9% of patients leading to 1.3 YLLs, being superior in 86.1% of cases with respect to alternative therapies (YLLs 4.8 years) and resulting in a number of two patients needed to operate to achieve one positive outcome. YLLs and NNTs depended on CRC stage, patient' age and comorbidities. For Stage I-II patients in the best clinical conditions (80-85 years without comorbidities), YLLs increased up to 4.1 years after surgery and up to 8.8 years without surgery (NNT 3). For Stage III patients, the NNT of surgery varied between 2 when they were in the best clinical conditions and 4 when they were older with high comorbidities. In Stage IV patients, the NNT ranged between 6 and 31. CONCLUSIONS: YLLs represents a novel approach to evaluate CRC prognosis. Stage I-III surgical patients can have a life expectancy similar to that of general population, being the NNT of surgery reasonably small compared with alternatives. Personalized comorbidity data are needed to confirm present findings.

An overview of 25 years of incidence, treatment and outcome of colorectal cancer patients.

Regarding the continuous changes in the diagnostic process and treatment of colorectal cancer (CRC), it is important to evaluate long-term trends which are relevant in giving direction for further research and innovations in cancer patient care. The aim of this study was to analyze developments in incidence, treatment and survival for patients diagnosed with CRC in the Netherlands. For this population-based retrospective cohort study, all patients diagnosed with CRC between 1989 and 2014 in the Netherlands were identified using data of the nationwide population-based Netherlands Cancer Registry (n = 267,765), with follow-up until January 1, 2016. Analyses were performed for trends in incidence, mortality, stage distribution, treatment and relative survival measured from the time of diagnosis. The incidence of both colon and rectal cancer has risen. The use of postoperative chemotherapy for Stage III colon cancer increased (14-60%), as well as the use of preoperative (chemo)radiotherapy for rectal cancer (2-66%). The administration of systemic therapy and metastasectomy increased for Stage IV disease patients. The 5-year relative survival increased significantly from 53 to 62% for colon cancer and from 51 to 65% for rectal cancer. Ongoing advancements in treatment, and also improvement in other factors in the care of CRC patients-such as diagnostics, dedicated surgery and pre- and postoperative care-lead to a continuous improvement in the relative survival of CRC patients. The increasing incidence of CRC favors the implementation of the screening program, of which the effects should be monitored closely.

Risk of Oral and Upper Gastrointestinal Cancers in Persons With Positive Results From a Fecal Immunochemical Test in a Colorectal Cancer Screening Program.

BACKGROUND & AIMS: European guidelines recommend screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT), with follow-up colonoscopies for individuals with positive test results. However, more than half of participants with positive results from the FIT are not found to have advanced neoplasia in the colonoscopy examination. Fecal occult blood might also come from the upper gastrointestinal (GI) tract, so perhaps we should consider esophagogastroduodenoscopy (EGD), to detect upper GI cancers. We aimed to determine how many individuals are found to have oral or upper GI cancers (oral cavity, throat, esophageal, gastric, or small bowel cancer) within 3 years after a positive or negative result from a FIT in a CRC screening program. METHODS: We performed a retrospective analysis of data from a pilot study of 3 rounds of biennial FIT-based screening for CRC in 2 regions in the west of the Netherlands, from 2006 through October 2012. Participants who developed oral or upper GI cancers were identified through linkage with the National Cancer Registry. We classified these cancers into 3 groups: those that developed in individuals with a positive result from a FIT but negative findings from colonoscopy (no advanced neoplasia), those that developed in individuals with a positive result from a FIT and a positive finding from colonoscopy (advanced neoplasia), and those that developed in individuals with negative results from a FIT. We compared oral and upper GI cancer incidence among groups. RESULTS: Among 16,165 screening participants, linkage identified 52 persons who developed an oral or upper GI cancer within 3 years after a FIT. We found no significant difference in incidence values between individuals with a positive vs a negative FIT result: 8 cancers developed in individuals with a positive result from a FIT (0.37%; 95% CI, 0.19-0.76) and 44 developed in individuals with a negative result from a FIT (0.31%; 95% CI, 0.23-0.42) (P = .65). Of the 8 individuals with a positive result from a FIT and an oral or upper GI cancer, 6 were diagnosed after negative findings from colonoscopy and 2 after positive findings from colonoscopy. We found that only 0.14% of all persons with a positive result from a FIT were diagnosed with a gastric or esophageal cancer within 3 years. CONCLUSION: In a study of individuals in the Netherlands undergoing screening for CRC by FIT, we found fewer than 1% of patients with a positive result from the FIT to receive a diagnosis of upper GI cancers within 3 years. Routine EGD investigation of individuals with positive results from a FIT and negative findings from colonoscopy is therefore not recommended. TrialRegister.nl, Number: NTR5385.

Neoadjuvant Therapy in Rectal Cancer Patients With Clinical Stage II to III Across European Countries: Variations and Outcomes.

BACKGROUND: Neoadjuvant therapy improves survival of patients with clinical stage II and III rectal cancer in clinical trials. In this study, we investigated the administration of neoadjuvant radiotherapy (neo-RT) and neoadjuvant chemoradiotherapy (neo-CRT) and its association with survival in resected patients in 2 European countries (The Netherlands and Sweden) and at 3 specialist centers. MATERIALS AND METHODS: Administration of neoadjuvant treatment (all registries) and overall survival after surgery in The Netherlands and Sweden were assessed. Hazard ratios (HRs) were obtained using Cox regression adjusted for potential confounders. RESULTS: A total of 16,095 rectal cancer patients with clinical stage II and III were eligible for analyses. Large variations in administration of neo-RT and neo-CRT were observed. Elderly patients less often received neo-RT and neo-CRT. Patients with stage III disease received neo-CRT more frequently than neo-RT. Administration of neo-RT versus surgery without neoadjuvant treatment was significantly associated with improved survival in The Netherlands (HR, 0.62; 95% confidence interval [CI], 0.53-0.73) as well as in Sweden (HR, 0.79; 95% CI, 0.69-0.90). Administration of neo-CRT was associated with enhanced survival in The Netherlands (HR, 0.62; 95% CI, 0.50-0.78) but not in Sweden (HR, 0.97; 95% CI, 0.80-1.18). The mortality of patients treated with neo-CRT compared with neo-RT showed inconsistent results in population-based centers. CONCLUSIONS: Our results support an association of neo-RT with enhanced survival among stage II and III rectal cancer patients. Comparing neo-CRT with neo-RT, larger variations and inconsistent results with respect to survival were observed across centers.

Interval Colorectal Cancer Incidence Among Subjects Undergoing Multiple Rounds of Fecal Immunochemical Testing.

BACKGROUND & AIMS: Among subjects screened for colorectal cancer (CRC) by the guaiac fecal occult blood test, interval cancers develop in 48% to 55% of the subjects. Data are limited on how many persons screened by fecal immunochemical tests (FIT), over multiple rounds, develop interval cancers. In the Netherlands, a pilot FIT-based biennial CRC screening program was conducted between 2006 and 2014. We collected and analyzed data from the program on CRCs detected during screening (SD-CRC) and CRCs not detected within the screening program (non-SD-CRC; such as FIT interval cancers, colonoscopy interval cancers, and cancer in nonparticipants). METHODS: Screenees with a negative FIT result received a letter explaining that no blood had been detected in the stool sample and were re-invited, if eligible, for screening biennially. Screenees with a positive FIT result (hemoglobin concentration of 10 µg Hb/g feces) were invited for consultation and scheduled for colonoscopy; results were collected. After the fourth round of FIT screening, the cohort was linked to the Netherlands Cancer Registry, through March 31, 2015; participant characteristics, data on tumor stage, location (at time of resection), and survival status were collected for all identified CRC cases. A reference group comprised all persons with CRC diagnosed in the Netherlands general population during the same period, in the same age range (50-76 years), who had not been offered CRC screening. The median time between invitations (2.37 years) was used as a cutoff to categorize participants within the FIT interval cancer category. We compared participant characteristics, tumor characteristics, and mortality among subjects with SD-CRC and with non-SD-CRC. RESULTS: A total of 27,304 eligible individuals were invited for FIT screening, of whom 18,716 (69%) participated at least once. Of these, 3005 (16%) had a positive result from the FIT in 1 of the 4 screening rounds. In total, CRC was detected in 261 participants: 116 SD-CRCs and 145 non-SD-CRCs (27 FIT interval cancers, 9 colonoscopy interval cancers, and 109 CRCs in nonparticipants). The FIT interval cancer proportion after 3 completed screening rounds was 23%. Participants with SD-CRC had more early-stage tumors than participants with non-SD-CRCs (P < .001). Of persons with SD-CRC and FIT interval cancers, significantly higher proportions survived (89% and 81%, respectively) compared with persons with colonoscopy interval cancers (44% survival) and nonparticipants with CRC (60% survival) (P < .001). CONCLUSIONS: In an analysis of data from a pilot FIT-based biennial screening program, we found that among persons screened by FIT, 23% developed FIT interval cancer. FIT therefore detects CRC with 77% sensitivity. The proportion of FIT interval cancers in FIT screening appears to be lower than that with guaiac fecal occult blood testing. Clinical trial registry: yes, www.trialregister.nl, trial number: NTR5385.

No Difference in Overall Survival Between Hospital Volumes for Patients With Colorectal Cancer in The Netherlands.

BACKGROUND: High-volume hospitals have been associated with improved patient outcomes for tumors with a relatively low incidence that require complex surgeries, such as esophageal and pancreatic cancer. The volume-outcome association for colorectal cancer is under debate. OBJECTIVE: This study investigated whether hospital volume for colorectal cancer is associated with surgical care characteristics and 5-year overall survival. DESIGN: This is a population-based study. SETTING: Data were gathered from the Netherlands Cancer Registry. Hospitals were grouped by volume for colon (<50, 50-74, 75-99, and ≥100 resections per year) and rectum (<20, 20-39, and ≥40 resections per year). PATIENTS: All of the patients with primary nonmetastatic colorectal cancer who underwent resection between 2005 and 2012 were included. MAIN OUTCOME MEASURES: Differences in surgical approach, anastomotic leakage, and postoperative 30-day mortality between hospital volumes were analyzed using χ tests and multivariable logistic regression analyses. Cox proportional hazard models were used to investigate the effect of hospital volume on overall survival. RESULTS: This study included 61,394 patients with colorectal cancer. In 2012, 31 of the 91 hospitals performed less than 50 colon cancer resections per year, and 21 of the 90 hospitals performed less than 20 rectal cancer resections per year. No differences in anastomotic leakage rates between hospital volumes were observed. Only small differences between hospital volumes were revealed for conversion of laparoscopic to open resection (OR of less than 50 versus 100 or more resections per year = 1.25 (95% CI, 1.06-1.46)) and postoperative 30-day mortality (colon: OR of less than 50 versus 100 or more resections per year = 1.17 (95% CI, 1.02-1.35); rectum: OR of less than 20 versus 40 or more resections per year = 1.42 (95% CI, 1.09-1.84)). No differences in overall survival were found between hospital volumes. LIMITATIONS: Although we adjusted for several patient and tumour characteristics, data regarding comorbidity, surgeon volume, local recurrences, and specific postoperative complications other than anastomotic leakage were not available. CONCLUSIONS: In the Netherlands, no differences in 5-year survival rates were revealed between hospital volumes for patients with nonmetastatic colorectal cancer.