Trends and Variation in the Use of Radiotherapy in Non-metastatic Rectal Cancer: a 14-year Nationwide Overview from the Netherlands.

AIMS: This study describes nationwide primary radiotherapy utilisation trends for non-metastasised rectal cancer in the Netherlands between 2008 and 2021. In 2014, both colorectal cancer screening and a new guideline specifying prognostic risk groups for neoadjuvant treatment were implemented. MATERIALS AND METHODS: Patients with non-metastasised rectal cancer in 2008-2021 (n = 37 510) were selected from the Netherlands Cancer Registry and classified into prognostic risk groups. Treatment was studied over time and age. Multilevel logistic regression analyses were carried out to identify factors associated with (i) radiotherapy versus chemoradiotherapy use for intermediate rectal cancer and (ii) chemoradiotherapy without versus with surgery for locally advanced rectal cancer. RESULTS: For early rectal cancer, the use of neoadjuvant radiotherapy decreased (15% to 5% between 2008 and 2021), whereas the use of endoscopic resections increased (8% in 2015, 17% in 2021). In intermediate-risk rectal cancer, neoadjuvant chemoradiotherapy (43% until 2011, 25% in 2015) shifted to radiotherapy (42% in 2008, 50% in 2015), the latter being most often applied in older patients. In locally advanced rectal cancer, the use of chemoradiotherapy without surgery increased (2-4% in 2008-2013, 17% in 2019-2021). Both neoadjuvant treatment in intermediate disease and omission of surgery following chemoradiotherapy in locally advanced disease varied with increasing age (odds ratio>75vs<50: 2.17, 95% confidence interval 1.54-3.06) and treatment region (Southwest and Northwest odds ratio 0.63, 95% confidence interval 0.42-0.93 and odds ratio 0.65, 95% confidence interval 0.44-0.95, respectively, compared with the North). CONCLUSION: Treatment patterns in non-metastasised rectal cancer significantly changed over time. Effects of both the national screening programme and the new treatment guideline were apparent, as well as a paradigm shift towards organ preservation (watch-and-wait). Observed regional variations may indicate adoption differences regarding new treatment strategies.

Peritoneal metastases in elderly patients with colorectal cancer.

BACKGROUND: With the introduction of cytoreductive surgery with intraperitoneal chemotherapy and the development of new systemic anti-cancer agents, the treatment of colorectal cancer (CRC) patients with peritoneal metastases has changed. Real-world data on the treatment of elderly patients and their clinical outcomes is lacking. METHODS: All CRC patients diagnosed with synchronous peritoneal metastases (SPM) during 2008-2019 (n = 7,748) were identified from the Netherlands Cancer Registry. Trends in treatment and postoperative mortality were described by age category (<70, 70-74, 75-79, ≥80 years) and period of diagnosis (2008-2013, 2014-2019). Kaplan-Meier curves were constructed, and log-rank tests were performed to evaluate differences in overall survival (OS). RESULTS: With increasing age, less patients received multimodality treatment and systemic treatment. Of the patients aged <70 years, 38% underwent multimodality treatment and 35% palliative systemic therapy, declining to 4% and 12% in patients ≥80 years. A large and increasing proportion of elderly patients did not receive cancer-directed treatment, this increased from 32% in 2008-2013 to 41% in 2014-2019 in 75-79 years old patients and from 52% to 65% in ≥80 years old. Postoperative mortality decreased in all age categories over time, OS remained stable. The median OS of elderly patients ranged from 8 months in 70-74 years old to 3 months in patients aged ≥80 years. DISCUSSION: Age strongly affects treatment of patients with SPM, with a large and increasing proportion of elderly patients not receiving cancer-directed treatment. Their prognosis remains very poor. There is a need for therapeutic options that are well tolerable for elderly patients.

Changes in rectal cancer treatment after the introduction of a national screening program; Increasing use of less invasive strategies within a national cohort.

AIM: Organ preserving treatment strategies and the introduction of a colorectal cancer-screening program have likely influenced the resection rates of rectal cancer. The aim of this study is to assess the influence of these developments on rectal cancer treatment and resection rates in the Netherlands. METHODS: Patients diagnosed with non-metastatic rectal cancer between 2013 and 2018, were selected from the Netherlands Cancer Registry. The distribution of surgical and neo-adjuvant treatment and resection rates were analyzed and compared over time. RESULTS: Between 2013 and 2018 22640 patients were diagnosed with non-metastatic rectal cancer. The incidence of early stage (cT1) disease increased from 141 (4%) in 2013 to 448 (12%) in 2018. The use of neoadjuvant radiotherapy and chemo-radiotherapy dropped from 39% to 21% and 34%-25%, respectively. A decrease in surgical resection rates (including TEM) was observed from 85% to 73%. The proportion of patients who underwent endoscopic resections increased from 3% to 10%. The decrease in surgical resection rates was larger in patients treated with neo-adjuvant chemo-radiotherapy. CONCLUSION: An increase in stage I disease is noted after the introduction of the screening program. Surgical resection rates for rectal cancer have fallen over time. Endoscopic resections due to more early-stage disease probably accounts for a large part of this decline. Furthermore, a watch and wait approach after neo-adjuvant chemo-radiotherapy may play an important role as well.

Treatment of clinical T1 rectal cancer in the Netherlands; a population-based overview of clinical practice.

INTRODUCTION: Local excision is increasingly used as an alternative treatment for radical surgery in patients with early stage clinical T1 (cT1) rectal cancer. This study provides an overview of incidence, staging accuracy and treatment strategies in patients with cT1 rectal cancer in the Netherlands. MATERIALS AND METHODS: Patients with cT1 rectal cancer diagnosed between 2005 and 2018 were included from the Netherlands Cancer Registry. An overview per time period (2005-2009, 2010-2014 and 2015-2018) of the incidence and various treatment strategies used, e.g. local excision (LE) or major resection, with/without neoadjuvant treatment (NAT), were given and trends over time were analysed using the Chi Square for Trend test. In addition, accuracy of tumour staging was described, compared and analysed over time. RESULTS: In total, 3033 patients with cT1 rectal cancer were diagnosed. The incidence of cT1 increased from 540 patients in 2005-2009 to 1643 patients in 2015-2018. There was a significant increased use of LE. In cT1N0/X patients, 9.2% received NAT, 25.5% were treated by total mesorectal excision (TME) and 11.4% received a completion TME (cTME) following prior LE. Overall accuracy in tumour staging (cT1 = pT1) was 77.3%, yet significantly worse in cN1/2 patients, as compared to cN0 patients (44.8% vs 77.9%, respectively, p < 0.001). CONCLUSION: Over time, there was an increase in the incidence of cT1 tumours. Both the use of neoadjuvant therapy and TME surgery in clinically node negative patients decreased significantly. Clinical accuracy in T1 tumour staging improved over time, but remained significantly worse in clinical node positive patients.

Treatment of metachronous colorectal cancer metastases in the Netherlands: A population-based study.

BACKGROUND: This study aimed to describe the treatment of metachronous colorectal cancer metastases in a recent population-based cohort. METHOD: Patients with stage I-III colorectal cancer (CRC), diagnosed between January 1st and June 30th, 2015 who were surgically treated with curative intent were selected from the Netherlands Cancer Registry. Follow-up was at least 3 years after diagnosis of the primary tumour. Treatment of metachronous metastases was categorized into local treatment, systemic treatment, and best supportive care. Overall survival was estimated using Kaplan-Meier method. RESULTS: Out of 5412 patients, 782 (14%) developed metachronous metastases, of whom 393 (50%) underwent local treatment (LT) with or without systemic therapy, 30% of patients underwent only systemic therapy (ST) and 19% only best supportive care (BSC). The most common metastatic site was the liver (51%) followed by lungs (33%) and peritoneum (22%). LT rates were 69%, 66%, and 44% for liver-only, lung-only and, peritoneal-only metastases respectively. Patients receiving LT and ST were significantly younger than patients receiving LT alone, while patients receiving BSC were significantly older than the other groups (p < 0.001). Patients with liver-only or lung-only metastases had a 3-year OS of 50.2% (43.3-56.7 95% CI) and 61.5% (50.7-70.6 95% CI) respectively. Patients with peritoneal-only disease had a lower 3-year OS, 18.1% (10.1-28.0 95% CI). CONCLUSION: Patients with metastases confined to the liver and lung have the highest rates of local treatment for metachronous metastatic colorectal cancer. The number of patients who underwent local treatment is higher than reported in previous Dutch and international studies.

Hospital variation in sphincter-preservation rates in rectal cancer treatment: results of a population-based study in the Netherlands.

BACKGROUND: This study aimed to examine the sphincter-preservation rate variations in rectal cancer surgery. The influence of hospital volume on sphincter-preservation rates and short-term outcomes (anastomotic leakage (AL), positive circumferential resection margin (CRM), 30- and 90-day mortality rates) were also analysed. METHODS: Non-metastasized rectal cancer patients treated between 2009 and 2016 were selected from the Netherlands Cancer Registry. Surgical procedures were divided into sphincter-preserving surgery and an end colostomy group. Multivariable logistic regression models were generated to estimate the probability of undergoing sphincter-preserving surgery according to the hospital of surgery and tumour height (low, 5 cm or less, mid, more than 5 cm to 10 cm, and high, more than 10 cm). The influence of annual hospital volume (less than 20, 20-39, more than 40 resections) on sphincter-preservation rate and short-term outcomes was also examined. RESULTS: A total of 20 959 patients were included (11 611 sphincter preservation and 8079 end colostomy) and the observed median sphincter-preservation rate in low, mid and high rectal cancer was 29.3, 75.6 and 87.9 per cent respectively. After case-mix adjustment, hospital of surgery was a significant factor for patients' likelihood for sphincter preservation in all three subgroups (P < 0.001). In mid rectal cancer, borderline higher rates of sphincter preservation were associated with low-volume hospitals (odds ratio 1.20, 95 per cent c.i. 1.01 to 1.43). No significant association between annual hospital volume and sphincter-preservation rate in low and high rectal cancer nor short-term outcomes (AL, positive CRM rate and 30- and 90-day mortality rates) was identified. CONCLUSION: This population-based study showed a significant hospital variation in sphincter-preservation rates in rectal surgery. The annual hospital volume, however, was not associated with sphincter-preservation rates in low, and high rectal cancer nor with other short-term outcomes.

Surgery for rectal cancer: Differences in resection rates among hospitals in the Netherlands.

AIM: Numerous quality improvement initiatives for rectal cancer surgery have focused on textbook outcome parameters. In these studies, resection rate and patients who did not undergo surgery are not included, but these parameters might help to evaluate the surgical care for rectal cancer. The aim of this study is to assess the variation of non-metastatic rectal cancer resection rates among hospitals and its effect on patient outcomes. METHODS: All patients diagnosed with non-metastatic rectal cancer between 2013 and 2018 were selected from the Netherlands Cancer Registry. Hospitals were categorized in quartiles according to resection rates. A multivariable logistic analysis was performed to determine variation in resection rate between these quartiles using a logistic regression analysis to correct for confounders. The association between resection rates and survival was analyzed using Kaplan-Meier method and Cox-regression analysis. RESULTS: A total of 22,530 patients were included in the analysis. Resection rates varied from 68 to 89% between hospitals. After multivariable analysis, resection rate remained significantly different among the quartiles when correcting for several factors (odds ratio (95%Confidence-interval) 1.71 (1.56-1.88), 2.42 (2.19-2.67), and 4.04 (3.61-4.53) for increasing resection rate quartiles, in reference to the lowest quartile). A higher resection rate was associated with better overall survival, in multivariable analysis this survival benefit could no longer be identified. CONCLUSION: There is a substantial variation in resection rates for rectal cancer among hospitals in the Netherlands with an impact on overall survival. This may be a relevant issue when analyzing the overall quality of rectal cancer care.

Hospital variance in neoadjuvant rectal cancer treatment and the influence of a national guideline update: Results of a nationwide population-based study.

INTRODUCTION: The aim of this study was to examine the hospital variation in neoadjuvant treatment of rectal cancer according to the different risk groups (low-, intermediate- and high-risk) and evaluate the influence on survival. MATERIALS AND METHODS: Patients with non-metastasized rectal cancer diagnosed between 2009 and 2016 were selected from the Netherlands Cancer Registry. The observed and case-mix adjusted distribution of the different neoadjuvant treatment schemes (none, radiotherapy (RT), chemoradiotherapy (CRT)) by hospital of diagnosis were generated for each risk group in the cohorts before and after the national guideline update of 2014. RESULTS: A total of 25,306 patients were included and after case-mix adjustment, hospital of diagnosis was found to have a significant impact on neoadjuvant treatment administration in each of the three risk groups (p < 0.001). Overall survival was however not influenced, except for the high-risk group where hospitals with highest rates of CRT were associated with a better 5-years overall survival (HR 0.79; p = 0.03). After guideline revision, the rate of patients in the low-risk group who did not undergo RT increased from a median of 30.8% to 90.5% (p < 0.001). CONCLUSION: Although a significant change in treatment was observed after revision of the national guidelines, a wide range of hospital variation still exists in administered neoadjuvant treatment in rectal cancer patients. High-risk rectal cancer patients had a better survival when treated in hospitals with the highest rates of CRT provided. In order to minimize treatment differences, further research into the causes of this variation and implementation of regionalized MDTs may be warranted.

Hospital volume and outcome in rectal cancer patients; results of a population-based study in the Netherlands.

BACKGROUND: Clinically staged T1-3 rectal cancer (cT1-3) is generally treated by total mesorectal excision(TME) with or without neoadjuvant therapy and sometimes requires beyond TME-surgery, whereas cT4 rectal cancer often requires both. This study evaluates the outcome of cT1-3 and cT4 rectal cancer according to hospital volume. METHODS: Patients undergoing rectal cancer surgery between 2005 and 2013 in the Netherlands were included from the National Cancer Registry. Hospitals were divided into low(1-20), medium(21-50) and high(>50 resections/year) volume for cT1-3 and low(1-4), medium(5-9) and high(≥10 resections/year) volume for cT4 rectal cancer. Cox-proportional hazards model was used for multivariable analysis of overall survival (OS). RESULTS: A total of 14.050 confirmed cT1-3 patients and 2.104 cT4 patients underwent surgery. In cT1-3 rectal cancer, there was no significant difference in 5-year OS related to high, medium and low hospital volume (70% vs. 69% vs. 69%). In cT4 rectal cancer, treatment in a high volume cT4 hospital was associated with a survival benefit compared to low volume cT4 hospitals (HR 0.81 95%CI 0.67-0.98) adjusted for non-treatment related confounders, but this was not significant after adjustment for neoadjuvant treatment. Patients with cT4-tumours treated in high volume hospitals had a significantly lower age, more synchronous metastases, more patients treated with neoadjuvant therapy and a higher pT-stage. CONCLUSION: Hospital volume was not associated with survival in cT1-3 rectal cancer. In cT4 rectal cancer, treatment in high volume cT4 hospitals was associated with improved survival compared to low volume cT4 hospitals, although this association lost statistical significance after correction for neoadjuvant treatment.

Tumor response after long interval comparing 5x5Gy radiation therapy with chemoradiation therapy in rectal cancer patients.

BACKGROUND: In the era of organ preserving strategies in rectal cancer, insight into the efficacy of preoperative therapies is crucial. The goal of the current study was to evaluate and compare tumor response in rectal cancer patients according to their type of preoperative therapy. METHODS: All rectal cancer patients diagnosed between 2005 and 2014, receiving radiation therapy (RT, 5 × 5Gy; N = 764) or chemoradiation therapy (CRT; N = 5070) followed by total mesorectal excision after an interval of 5-15 weeks were retrieved from the nationwide Netherlands Cancer registry. Logistic regression was used for multivariable analysis. RESULTS: Median age of patients treated with RT was 76 years (range 28-92) compared to 64 years (range 21-92) for patients treated with CRT (P < 0.001). Patients treated with RT had a significantly lower clinical stage (P < 0.001). A complete pathologic response (ypT0N0) was found in 9.3% of patients treated with RT, significantly less than in patients treated with CRT (17.5%; odds ratio [OR] 0.37, 95% confidence interval [CI] 0.24-0.57). A good response (ypT0-1N0) was observed in 17.5% of patients treated with RT and in 22.6% of patients treated with CRT (OR 0.70, 95% CI 0.51-0.95). Histological subtype, clinical stage and distance to anus were identified as independent predictors for tumor response. CONCLUSIONS: Despite a more advanced clinical stage, complete pathologic response was more common in patients treated with CRT than in patients treated with RT. Prospective trials are needed to establish the differences in other outcome parameters, including the impact on organ preserving strategies.

[National population screening for colorectal carcinoma in the Netherlands: results of the first years since the implementation in 2014]. / Landelijk bevolkingsonderzoek naar colorectaal carcinoom.

OBJECTIVE: To describe the effect of population screening for colorectal carcinoma (CRC) with the faecal immunochemical test, introduced in 2014, on the incidence of CRC in the Netherlands and to analyse differences between patient and tumour characteristics, stage distribution and treatment of carcinomas that were screening-detected and were not detected by screening (non-screening-detected). DESIGN: Retrospective observational study. METHOD: We analysed data from the Netherlands Cancer Registry. We selected all CRCs diagnosed in the 2010-2016 period and calculated incidence rates standardised for the European population. For comparison between screening-detected and non-screening-detected carcinomas, we selected all CRCs diagnosed in 2015. RESULTS: The number of newly diagnosed CRCs rose from 13,028 in 2013 to 15,185 in 2014 and to 15,807 in 2015. This increase could only be seen for the birth years of people who had been invited for population screening during that particular year. The percentage of men was higher for screening-detected carcinomas than for non-screening-detected carcinomas (62% vs 55%). Screening-detected carcinomas were also more often in the left side of the colon (76% vs 64%). The percentage of patients with stage I CRC was higher in the group with screening-detected carcinomas (48% vs 16%). Patients with screening-detected carcinomas more often underwent local treatment or only resection without adjuvant or neoadjuvant treatment than the patients with non-screening-detected carcinomas. CONCLUSION: During the first years after the introduction of population screening, the incidence of CRC has increased as the result of earlier detection. Screening-detected carcinomas have a more favourable stage distribution and these patients are undergoing less-invasive treatment more often.

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

Ethnic differences in colon cancer care in the Netherlands: a nationwide registry-based study.

BACKGROUND: Ethnic differences in colon cancer (CC) care were shown in the United States, but results are not directly applicable to European countries due to fundamental healthcare system differences. This is the first study addressing ethnic differences in treatment and survival for CC in the Netherlands. METHODS: Data of 101,882 patients diagnosed with CC in 1996-2011 were selected from the Netherlands Cancer Registry and linked to databases from Statistics Netherlands. Ethnic differences in lymph node (LN) evaluation, anastomotic leakage and adjuvant chemotherapy were analysed using stepwise logistic regression models. Stepwise Cox regression was used to examine the influence of ethnic differences in adjuvant chemotherapy on 5-year all-cause and colorectal cancer-specific survival. RESULTS: Adequate LN evaluation was significantly more likely for patients from 'other Western' countries than for the Dutch (OR 1.09; 95% CI 1.01-1.16). 'Other Western' patients had a significantly higher risk of anastomotic leakage after resection (OR 1.24; 95% CI 1.05-1.47). Patients of Moroccan origin were significantly less likely to receive adjuvant chemotherapy (OR 0.27; 95% CI 0.13-0.59). Ethnic differences were not fully explained by differences in socioeconomic and hospital-related characteristics. The higher 5-year all-cause mortality of Moroccan patients (HR 1.64; 95% CI 1.03-2.61) was statistically explained by differences in adjuvant chemotherapy receipt. CONCLUSION: These results suggest the presence of ethnic inequalities in CC care in the Netherlands. We recommend further analysis of the role of comorbidity, communication in patient-provider interaction and patients' health literacy when looking at ethnic differences in treatment for CC.

Regional and inter-hospital differences in the utilisation of liver surgery for patients with synchronous colorectal liver metastases in the Netherlands.

BACKGROUND: The objective of this study was to map referral patterns in patients with synchronous colorectal liver metastases (SCLM) and to investigate if type, volume and location of the hospital of diagnosis are associated with whether or not patients underwent liver resection. METHODS: This population-based study includes all patients diagnosed with SCLM between 2008 and 2012, based on the Netherlands Cancer Registry. To study inter-hospital variation, the proportion of patients undergoing liver surgery was calculated per hospital of diagnosis. Multivariable multilevel logistic regression analysis was used to investigate the association between hospital characteristics and liver resection. RESULTS: Of 10,520 patients with SCLM, 12% (n = 1259) underwent liver surgery. Of these patients, 58% (n = 733) were referred to another hospital to undergo liver surgery. In 53% of the patients (n = 647), liver resection was performed in a university hospital, in 39% (n = 482) in a dedicated liver centre and in 8% (n = 102) in a general hospital. There was a large inter-hospital variation in the proportion of patients undergoing liver resection (2-26%). In a multilevel logistic regression model, the odds of undergoing liver surgery were higher when patients were diagnosed in hospitals where liver surgery was performed compared with the general hospitals (dedicated liver centre: odds ratio 1.36 [95% confidence intervals 1.08-1.70], university hospital: odds ratio 1.69 [95% confidence intervals 1.22-2.34]). CONCLUSION: There is a large inter-hospital and inter-regional variation in the utilisation of liver resection. Patients diagnosed with SCLM in expert centres had a higher chance of undergoing liver resection.

Incidence of second tumors after treatment with or without radiation for rectal cancer.

Background: The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. Patients and methods: Data on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray's competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression. Results: The cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0-27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12-1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68-0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46-0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11-2.00). Conclusions: Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.

Treatment Interval between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer Patients: A Population-Based Study.

BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) has been widely implemented in the treatment of rectal cancer patients, but optimal timing of surgery after neoadjuvant therapy is unclear. The purpose of this study was to evaluate the effects of prolonged intervals between long-course CRT and surgery in rectal cancer patients. METHODS: Data on all rectal cancer patients diagnosed between 2006 and 2011 were retrieved from the population-based Netherlands Cancer Registry; the main outcome parameters were pathologic complete response (pCR) and overall survival (OS). Outcomes were reported separately for patients with early tumors (ETs; N = 217) and locally advanced rectal cancer (LARC; N = 1073). Patients were divided into 2-week interval groups according to treatment interval, ranging from 5-6 to 13-14 weeks. Kaplan-Meier curves, and logistic regression and Cox regression models were used for data analysis. RESULTS: No significant difference in pCR rate was observed for ET patients according to treatment interval. Compared with a treatment interval of 7-8 weeks, pCR rates in LARC patients were higher after 9-10 weeks (18.4 %; odds ratio [OR] 1.56, 95 % CI 1.03-2.37) and 11-12 weeks of treatment interval (20.8 %; OR 1.94, 95 % CI 1.15-3.26). Treatment interval did not influence OS in ET or LARC patients. CONCLUSIONS: Treatment intervals of 9-12 weeks between surgery and CRT seem to improve the chances of pCR in LARC patients, without an effect on OS. The length of treatment interval did not affect outcomes in patients with ET. The ongoing search for minimally invasive surgery drives the need for exploration of factors that improve pathologic response.

Participation, yield, and interval carcinomas in three rounds of biennial FIT-based colorectal cancer screening.

BACKGROUND: The effectiveness of colorectal cancer screening programs based on the fecal immunochemical test (FIT) is influenced by program adherence during consecutive screening rounds. We aimed to evaluate the participation rate, yield, and interval cancers in a third round of biennial CRC screening using FIT and to compare those with the first and the second screening round. METHODS: A total of 3566 average-risk individuals aged 50-75 years were invited to participate in a third round of biennial FIT-based CRC screening. All FIT positives were recommended to undergo colonoscopy. We merged our data with the national cancer registry in the Netherlands to identify all non-screen-detected cancers in our cohort. RESULTS: Of the invitees, 2142 (60%) returned the FIT in this third screening round, compared to 56% in the second round and 57% in the first round. Overall, 153 of the third-round participants (7.1%) had a positive FIT result, versus 7.9% in the second round and 8.1% in the first round (P=0.05). Of all FIT positives, 123 (80%) underwent colonoscopy. Within this group, 33 persons had advanced neoplasia. The predictive value of FIT positivity for advanced neoplasia was 27% (33/123), compared to 42% in the second round and 54% in the first round - a significant decline (P<0.01). CONCLUSION: In an FIT-based screening program, participation rates remained stable over consecutive biennial screening rounds, while the FIT positivity rate and positive predictive value for advanced neoplasia gradually declined. Cancers in non-participants are significantly more advanced in staging than cancers in participants in the first round of screening.

Differences in pre-operative treatment for rectal cancer between Norway, Sweden, Denmark, Belgium and the Netherlands.

Several studies have shown remarkable differences in colorectal cancer survival across Europe. Most of these studies lacked information about stage and treatment. In this study we compared short-term survival as well as differences in tumour stage and treatment strategies between five European countries: Norway, Sweden, Denmark, Belgium, and the Netherlands. For this retrospective cohort study all patients aged 18 years or older and operated on adenocarcinoma of the rectum without distant metastases and diagnosed in 2008 and 2009 were selected in national audit registries from Norway, Sweden, Denmark, Belgium, and the Netherlands. Differences in pre-operative treatment between the countries were compared using univariable and multivariable logistic regression. One year relative survival and one year relative excess risk of death (RER) were compared between the five countries. Large variation in the use of preoperative radiotherapy and chemoradiation was found between the countries. Even though, there was little variation in relative survival between the countries, except Sweden, which had a significant better one year RER of death among the elderly patients after adjustment. The differences in survival are expected to be caused by differences in peri-operative care, selection of patients, and especially management of elderly patients. The effects of preoperative treatment are expected to be seen on long term follow-up.

The Dutch surgical colorectal audit.

INTRODUCTION: In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated by the Dutch Institute for Clinical Auditing (DICA). This article illustrates key elements of the DSCA and results of three years of auditing. METHODS: Key elements include: a leading role of the professional association with integration of the audit in the national quality assurance policy; web-based registration by medical specialists; weekly updated online feedback to participants; annual external data verification with other data sources; improvement projects. RESULTS: In two years, all Dutch hospitals participated in the audit. Case-ascertainment was 92% in 2010 and 95% in 2011. External data verification by comparison with the Netherlands Cancer Registry (NCR) showed high concordance of data items. Within three years, guideline compliance for diagnostics, preoperative multidisciplinary meetings and standardised reporting increased; complication-, re-intervention and postoperative mortality rates decreased significantly. DISCUSSION: The success of the DSCA is the result of effective surgical collaboration. The leading role of the ASN in conducting the audit resulted in full participation of all colorectal surgeons in the Netherlands. By integrating the audit into the ASNs' quality assurance policy, it could be used to set national quality standards. Future challenges include reduction of administrative burden; expansion to a multidisciplinary registration; and addition of financial information and patient reported outcomes to the audit data.

Prognostic factors for locoregional recurrences in colon cancer.

BACKGROUND: There is increased interest in locoregional recurrences of rectal cancer. Despite comparable locoregional recurrence rates in colon cancer, only a few studies on locoregional recurrences among colon cancer patients have been published. This study was designed to identify prognostic factors for locoregional recurrences among patients with colon cancer in the Netherlands. METHODS: The study population was composed of patients who underwent radical surgical resections for invasive colon carcinoma, diagnosed in three regions of the Netherlands from 2000 to 2003. The Kaplan-Meier method was used to calculate 5-year locoregional recurrence rates (LRR). Conditional hazard rates were estimated by the life-table method. Multivariate Cox regression analyses were performed to identify prognostic factors and to calculate a Locoregional Recurrence Risk Score (LRRS). RESULTS: In total 127 of 2,282 patients developed locoregional recurrences within 5 years (LRR 6.4%). The risk of developing a locoregional recurrence was highest at 0.5-1 year after surgery. Patients with left-sided tumors, T3-T4 tumors, and positive lymph nodes and those who did not receive adjuvant chemotherapy were more likely to develop locoregional recurrences. Four risk groups based on the LRRS were defined. Five-year LRR was 2.5% for the very low-risk group and 25.1% for the high-risk group. CONCLUSIONS: Although the locoregional recurrence rate in this study was relatively low, it remains a considerable problem. Identifying individual patients who might benefit from adjuvant chemotherapy may reduce the locoregional recurrence rate.