Differences in treatment of stage I colorectal cancers: a population-based study of colorectal cancers detected within and outside of a screening program.

BACKGROUND: Screen-detected colorectal cancers (CRCs) are often treated less invasively than stage-matched non-screen-detected CRCs, but the reasons for this are not fully understood. This study evaluated the treatment of stage I CRCs detected within and outside of the screening program in the Netherlands. METHODS : Data from the Netherlands Cancer Registry for all stage I CRCs diagnosed between January 1, 2008 and December 31, 2020 were analyzed, comparing patient, tumor, and treatment characteristics of screen-detected and non-screen-detected stage I CRCs. Multivariable logistic regression was used to assess the association between treatment (local excision only vs. surgical oncologic resection) and patient and tumor characteristics, stratified for T stage and tumor location. RESULTS: Screen-detected stage I CRCs were relatively more often T1 than T2 compared with non-screen-detected stage I CRCs (66.9 % vs. 53.3 %; P < 0.001). When only T1 tumors were considered, both screen-detected colon and rectal cancers were more often treated with local excision only than non-screen-detected T1 cancers (odds ratio [OR] 2.19, 95 %CI 1.93-2.49; and OR 1.29, 95 %CI 1.05-1.59, respectively), adjusted for sex, tumor location, lymphovascular invasion (LVI) status, and tumor differentiation. CONCLUSIONS : Less invasive treatment of screen-detected stage I CRC is partly explained by the higher rate of T1 cancers compared with non-screen-detected stage I CRCs. T1 stage I screen-detected CRCs were also more likely to undergo less invasive treatment than non-screen-detected CRCs, adjusted for risk factors such as LVI and tumor differentiation. Future research should investigate whether the choice of local excision was related to unidentified cancer-related factors or the expertise of the endoscopists.

Initial Impact of National CRC Screening on Incidence and Advanced Colorectal Cancer.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) aims to decrease CRC incidence and mortality. Biennial fecal immunochemical test screening started in the Netherlands in 2014 for individuals 55-75 years of age. This study investigated the effect of screening on stage-specific incidence, with focus on stage III and IV CRC. METHODS: Inhabitants diagnosed with CRC in 2009-2018 were included. CRC incidence per stage, year, and detection method (ie, screen-detected vs clinically detected) was evaluated. Patient, tumor, and treatment characteristics, and survival of patients with stage III and IV CRC, were compared according to the detection method. RESULTS: Included were 140,649 CRCs in 136,882 patients. An initial peak of stage I-III CRC diagnoses after initiation of screening was followed by a continuous decrease within screening-eligible ages. Total CRC incidence remained higher than before screening, although stage II and IV CRC incidence decreased below prescreening levels. Screen-detected CRCs were significantly more frequently located in the left-sided colon (stage III; 43.7% vs 30.9%; stage IV: 45.1% vs 36.1%), and the primary tumor resection rate was higher (stage III colon: 99.8% vs 99.0%, rectum: 97.3% vs 89.7%; stage IV colon: 65.4% vs 56.6%, rectum: 47.3% vs 33.5%). Patients with screen-detected stage IV CRC had significantly more often single-organ metastases (74.5% vs 57.0%; P < .001) and more frequently received treatment with curative intent (colon: 41.3% vs 27.4%; rectum: 33.8% vs 24.6%). Overall survival significantly improved for patients with screen-detected CRCs (stage III: P < .001; stage IV: P < .001). CONCLUSIONS: Five years after the start of a nationwide CRC screening program, a decrease in stage II and IV CRC incidence was observed. Patients with screen-detected stage III and stage IV CRC had less extensive disease and improved survival compared with those with clinically detected CRC.

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases.

BACKGROUND: Patients who develop early extrahepatic recurrence (EHR) may not benefit from local treatment of colorectal liver metastases (CRLMs). This study aimed to develop a prediction model for early EHR after local treatment of CRLMs using a national data set. METHODS: A Cox regression prediction model for EHR was developed and validated internally using data on patients who had local treatment for CRLMs with curative intent. Performance assessment included calibration, discrimination, net benefit, and generalizability by internal-external cross-validation. The prognostic relevance of early EHR (within 6 months) was evaluated by landmark analysis. RESULTS: During a median follow-up of 35 months, 557 of the 1077 patients had EHR and 249 died. Median overall survival was 19.5 (95 per cent c.i. 15.6 to 23.0) months in patients with early EHR after CRLM treatment, compared with not reached (45.3 months to not reached) in patients without an early EHR. The EHR prediction model included side and stage of the primary tumour, RAS/BRAFV600E mutational status, and number and size of CRLMs. The range of 6-month EHR predictions was 5.9-56.0 (i.q.r. 12.9-22.0) per cent. The model demonstrated good calibration and discrimination. The C-index through 6 and 12 months was 0.663 (95 per cent c.i. 0.624 to 0.702) and 0.661 (0.632 to 0.689) respectively. The observed 6-month EHR risk was 6.5 per cent for patients in the lowest quartile of predicted risk compared with 32.0 per cent in the highest quartile. CONCLUSION: Early EHR after local treatment of CRLMs can be predicted.

Towards patient-led follow-up after curative surgical resection of stage I, II and III colorectal cancer (DISTANCE-trial): a study protocol for a stepped-wedge cluster-randomised trial.

BACKGROUND: Colorectal cancer (CRC) is among the most frequently diagnosed cancers. Approximately 20-30% of stage I-III CRC patients develop a recurrent tumour or metastases after curative surgical resection. Post-operative follow-up is indicated for the first five years after curative surgical resection. As intensified follow-up after curative surgical resection has shown no effect on survival, patient organisations and policy makers have advocated for a more patient-centred approach to follow-up. The objective of this study is to successfully implement patient-led, home-based follow-up (PHFU) in six hospitals in The Netherlands, with as ultimate aim to come to a recommendation for a patient-centred follow-up schedule for stage I-III CRC patients treated with surgical resection with curative intent. METHODS: This study is designed as a stepped-wedge cluster-randomised trial (SW-CRT) in six participating centres. During the trial, three centres will implement PHFU after six months; the other three centres will implement PHFU after 12 months of inclusion in the control group. Eligible patients are those with pT2-4N0M0 or pT1-4N1-2M0 CRC, who are 18 years or older and have been free of disease for 12 months after curative surgical resection. The studied intervention is PHFU, starting 12 months after curative resection. The in-hospital, standard-of-care follow-up currently implemented in the participating centres functions as the comparator. The proportion of patients who had contact with the hospital regarding CRC follow-up between 12-24 months after curative surgical resection is the primary endpoint of this study. Quality of life, fear of cancer recurrence, patient satisfaction, cost-effectiveness and survival are the secondary endpoints. DISCUSSION: The results of this study will provide evidence on whether nationwide implementation of PHFU for CRC in The Netherlands will be successful in reducing contact between patient and health care provider. Comparison of PROMs between in-hospital follow-up and PHFU will be provided. Moreover, the cost-effectiveness of PHFU will be assessed. TRIAL REGISTRATION: Dutch Trail Register (NTR): NL9266 (Registered on January 1st, 2021).

Surgical treatment and overall survival in patients with right-sided obstructing colon cancer-a nationwide retrospective cohort study.

PURPOSE: The aim of this study was to compare baseline characteristics, 90-day mortality and overall survival (OS) between patients with obstructing and non-obstructing right-sided colon cancer at a national level. METHODS: All patients who underwent resection for right-sided colon cancer between January 2015 and December 2016 were selected from the Netherlands Cancer Registry and stratified for obstruction. Primary outcome was 5-year OS after excluding 90-day mortality as assessed by the Kaplan-Meier and multivariable Cox regression analysis. RESULTS: A total of 525 patients (7%) with obstructing and 6891 patients (93%) with non-obstructing right-sided colon cancer were included. Patients with right-sided obstructing colon cancer (OCC) were older and had more often transverse tumour location, and the pathological T and N stage was more advanced than in those without obstruction (p < 0.001). The 90-day mortality in patients with right-sided OCC was higher compared to that in patients with non-obstructing colon cancer: 10% versus 3%, respectively (p < 0.001). The 5-year OS of those surviving 90 days postoperatively was 42% in patients with OCC versus 73% in patients with non-obstructing colon cancer, respectively (p < 0.001). Worse 5-year OS was found in patients with right-sided OCC for all stages. Obstruction was an independent risk factor for decreased OS in right-sided colon cancer (HR 1.79, 95% CI 1.57-2.03). CONCLUSION: In addition to increased risk of postoperative mortality, a stage-independent worse 5-year OS after excluding 90-day mortality was found in patients with right-sided OCC compared to patients without obstruction.

Limited impact of the COVID-19 pandemic on colorectal cancer care in the Netherlands in 2020.

PURPOSE: The COVID-19 pandemic had a major impact on the health services worldwide. We aimed to investigate the impact of the pandemic on colorectal cancer (CRC) care in the Netherlands in 2020. METHODS: CRC patients, diagnosed in 2018-2020 in the Netherlands, were selected from the Netherlands Cancer Registry (NCR). The year 2020 was divided in four periods reflecting COVID-19 developments in the Netherlands (pre-COVID, 1st peak, recovery period, 2nd peak) and compared with the same periods in 2018/2019. Patient characteristics and treatment were compared using the Chi-squared test. Median time between diagnosis and treatment, and between (neo)adjuvant therapy and surgery were analyzed by the Mann-Whitney U test. RESULTS: In total, 38,021 CRC patients were diagnosed in 2018/2019 (n = 26,816) and 2020 (n = 11,205). Median time between diagnosis and initial treatment decreased on average 4 days and median time between neoadjuvant radiotherapy and surgery in clinical stage II or III rectal cancer patients increased on average 34 days during the three COVID-19 periods compared to the same periods of 2018/2019. The proportion of colon cancer patients that underwent elective surgery significantly decreased with 3.0% during the 1st peak. No differences were found in the proportion of patients who received (neo)adjuvant therapy, systemic therapy, or no anti-cancer treatment. CONCLUSION: Only minor changes in the care for CRC patients occurred during the COVID-19 pandemic, mostly during the 1st peak. In conclusion, the impact on CRC care in the Netherlands was found to be limited. However, long-term effects cannot be precluded.

Interregional practice variations in the use of local therapy for synchronous colorectal liver metastases in the Netherlands.

BACKGROUND: The aim of this study was to evaluate the Dutch regional practice variation in treatment of synchronous colorectal liver metastases (CRLM) over time and assess their impact on patients survival. METHODS: Two cohorts of patients with synchronous CRLM were selected from the Netherlands Cancer Registry (NCR). All patients diagnosed between 2014 and 2018 were selected to analyze interregional practice variations in local therapy (LT) with multivariable logistic regression. Overall survival (OS) was assessed for patients diagnosed from 2008 to 2013 using Kaplan Meier method and Cox regression analyses. RESULTS: The proportion of patients who underwent LT increased from 15.5% to 21.9%. Interregional use of LT varied from 19.1% to 25.0%. Multivariable logistic regression showed significant differences between regions in the use of LT (p = 0.001) in 2014-2018. There was no association between OS and region of diagnosis for patients who underwent LT after correction for confounders.The use of LT for CRLM increased from 15.5% in 2008-2013 to 21.9% in 2014-2018. Three-year OS increased from 16% to 19% respectively. CONCLUSION: Interregional practice variations have decreased. The remaining differences are not associated with OS. The use of local therapy and 3-year overall survival have increased over time. Local practice should be monitored to prevent undesirable variation in outcomes.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Informing metastatic colorectal cancer patients by quantifying multiple scenarios for survival time based on real-life data.

Reported median overall survival (mOS) in metastatic colorectal cancer (mCRC) patients participating in systemic therapy trials has increased to over 30 months. It is uncertain whether trial results translate to real-life populations. Moreover, patients prefer presentation of multiple survival scenarios. Population-based data of all stage IV CRC patients diagnosed between 2008 and 2016 were obtained from the Netherlands Cancer Registry, which has a case ascertainment completeness surpassing 95%. We calculated the following percentiles (scenarios) of OS per year of diagnosis for the total population, and for treatment subgroups: 10th (best-case), 25th (upper-typical), 50th (median), 75th (lower-typical) and 90th (worst-case). Twenty-five percent of patients did not receive any antitumor treatment. From 2008 to 2016, mOS of the total population (n = 27275) remained unchanged at approximately 12 months. OS improved only for the upper-typical and best-case patients; by 4.2 to 29.1 months (P < .001), and by 6 to 62 months (P < .001), respectively. No clinically relevant change was observed among patients who received systemic therapy, with mOS close to 15 months and best-case scenario approximately 40 months. A clinically relevant improvement in survival over time was observed in patients who initially received metastasectomy and/or HIPEC only. In contrast to the wide belief based on trial data that mOS of mCRC patients receiving systemic therapy has improved substantially, improvement could not be demonstrated in our real-life population. Clinicians should consider quoting multiple survival scenarios based on real-life data instead of point estimates from clinical trials, when informing patients about their life expectancy.

Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era.

BACKGROUND: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy. METHODS: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified. RESULTS: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8-19.6) with antitumour therapy and 2.5 months (1.8-3.5) in untreated patients. OS1 was 12.8 months (10.7-15.2) and OS2 6.2 months (5.4-8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients. CONCLUSION: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.

Ethnic Inequalities in Rectal Cancer Care in a Universal Access Healthcare System: A Nationwide Register-Based Study.

BACKGROUND: Ethnic inequalities in colorectal cancer care were reported previously in the United States. Studies specifically reporting on ethnic inequalities in rectal cancer care are limited. OBJECTIVE: This study aimed to explore potential ethnic inequalities in rectal cancer care in the Netherlands. DESIGN: This was a nationwide, population-based observational study. SETTINGS: The study linked data of the Netherlands Cancer Registry with the Dutch population registry and the Social Statistics Database of Statistics Netherlands. Data were analyzed using stepwise multivariable logistic regression models. PATIENTS: All of the patients diagnosed with rectal carcinoma in 2003-2011 in the Netherlands (N = 27,159) were included. MAIN OUTCOME MEASURES: We analyzed 2 rectal cancer treatment indicators (preoperative radiotherapy and sphincter-sparing surgery) and 2 indicators of short-term outcome of rectal cancer surgery (anastomotic leakage and 30-day postoperative mortality). RESULTS: Patients of Western non-Dutch and non-Western origin with rectal cancer were significantly younger and had a higher tumor stage than ethnic Dutch patients. Considering preoperative radiotherapy, anastomotic leakage, and 30-day postoperative mortality, no ethnic inequalities were detected. After adjustment for age, sex, disease characteristics, and socioeconomic status, Western non-Dutch and non-Western patients were significantly more likely to receive sphincter-sparing surgery than ethnic Dutch patients (OR = 1.27 (95% CI, 1.04-1.55) and OR = 1.57 (95% CI, 1.02-2.42)). LIMITATIONS: This study was limited by the relatively low numbers of non-Dutch patients with rectal cancer. CONCLUSIONS: Non-Dutch ethnic origin was associated with a higher rate of sphincter-sparing surgery. The absence of ethnic inequalities in preoperative radiotherapy, anastomotic leakage, and 30-day postoperative mortality suggests that ethnic minority patients have similar chances of optimal rectal cancer care outcomes as Dutch patients.

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.

Long-term effects of a regional care pathway for patients with rectal cancer.

PURPOSE: Introducing care pathways is seen as a method to realise patient-focussed care conform evidence-based guidelines. The goal of this study is to determine the long-term effects of a regional care pathway for patients with rectal cancer. PATIENTS AND METHODS: Data on almost 400 patients with rectal carcinoma from three hospitals were obtained from the Netherlands Cancer Registry and the Dutch Surgical Colorectal Audit. Results on seven structure and process indicators were analysed and compared before and at two time points after implementing a regional care pathway over a total period from 2007 to 2012. To determine motivation and interpret the results, relevant professionals of the participating hospitals were interviewed. RESULTS: After implementing the care pathway, the performance of computed tomography (CT) scans in the diagnostic phase significantly improved (p = 0.007/0.07). The number of patients discussed in the preoperative multidisciplinary team (MDT) meeting improved significantly (p = <0.001), and after implementing the care pathway, 94% of the patients were discussed. Further, a significant reduction in time between the first tumour biopsy and the MDT meeting was realised (p = 0.01). Professionals stated that the regional care pathway has led to more clarity about the patient route and more awareness about complying with evidence-based guidelines. CONCLUSIONS: The regional care pathway provided a solid basis for uniforming care, working according evidence-based guidelines and further cooperation on regional level. For mainly the waiting and throughput times, the guidelines and norms had probably a stronger effect on the results than the care pathway.

Metachronous metastases from colorectal cancer: a population-based study in North-East Netherlands.

PURPOSE: The main cause of death of colorectal cancer patients is metastatic disease. Approximately 20-25% of the patients present with metastases at time of diagnosis. The clinical course of patients who develop metachronous metastases, however, is less clear. The aims of this study were to describe the incidence, treatment and survival of patients with metachronous metastases from colorectal cancer and to determine risk factors for developing metachronous metastases. METHODS: From the Netherlands Cancer Registry, patients diagnosed with colorectal carcinoma in the period 2002-2003 in North-East Netherlands were selected. Patients were followed for 5 years after diagnosis of the primary tumour. Kaplan-Meier method and Cox regression analyses were used to determine predictors for developing metastases and to analyse overall survival. RESULTS: In total, 333 of 1743 (19%) patients developed metachronous metastases. The majority (83%) of these metastases were diagnosed within 3 years, and the most frequent site was the liver. Patients with advanced stage and patients with tumours in the descending colon or in the rectum were more likely to develop metastases. Approximately 10% of all patients underwent intentionally curative treatment for their metastases, with a 5-year survival rate of 60%. Treatment of metastases and pathologic N (pN) status were independent prognostic factors for overall survival. CONCLUSIONS: Site and stage of the primary tumour were predictors for developing metachronous metastases. A limited number of patients with metastatic disease were treated with a curative intent. These patients had a good prognosis. Therefore, focus should be on identifying more patients who could benefit from curative treatment.

Adjuvant chemotherapy in patients with clinically node-negative but pathologically node-positive rectal cancer in the Netherlands: A retrospective analysis.

INTRODUCTION: Accurate clinical staging of rectal cancer is hampered by suboptimal sensitivity of MRI in the detection of regional lymph node metastases. Consequently, some patients may be understaged and have been withheld neoadjuvant (chemo)radiotherapy in retrospect. Although Dutch guidelines do not advocate adjuvant chemotherapy (ACT) in rectal cancer, some of these clinically understaged patients receive ACT according to local policy. We aim to assess the benefit of ACT in these patients. METHODS: Population-based data from patients with clinically node-negative (cN0) but pathologically node-positive (pN+) rectal cancer that underwent total mesorectal excision (TME) without neoadjuvant treatment between 2008 and 2018 were obtained from the Netherlands Cancer Registry. Missing data were handled by multiple imputation. Stabilised inverse probability treatment weighting (sIPTW) was used to balance clinical characteristics. Overall survival (OS) was compared in ACT and non-ACT patients. RESULTS: Of 34,724 patients, 13,861 had cN0 disease of whom 3016 were pN+ (21.8%). 1466 (48.6%) of these patients underwent upfront TME and were included. Median follow-up was 84 months (95% confidence interval [CI] 76-97) versus 79 months (95% CI 77-81) in patients that did (n = 290, 19.8%) and did not (n = 1176, 80.2%) receive ACT, respectively. After sIPTW adjustment, ACT was associated with improved OS (hazard ratio 0.70; 95% CI 0.49-0.99; p = 0.04). The estimated 5-year OS rate was 74.2% versus 65.3%, respectively. CONCLUSION: In this population-based cohort of patients with cN0 but pN+ rectal cancer who underwent upfront TME, ACT was associated with a significant OS benefit. These data support to discuss ACT in this population.

Impact of colorectal cancer screening on survival after metachronous metastasis.

BACKGROUND: An increasing proportion of colorectal cancer (CRC) cases in Europe are detected by screening with faecal immunochemical testing (FIT). Previous studies showed that population screening with FIT leads to a decrease in CRC incidence and to detection at an earlier stage. However, approximately twenty percent of patients with CRC without metastases at initial diagnosis still develop metachronous metastases. We investigated the association between detection mode of the primary tumor and overall survival (OS) after metachronous metastasis in patients with CRC. METHODS: Nationwide registry-based data was obtained of 794 patients who developed metachronous metastases after being diagnosed with stage I-III CRC between January and June 2015. With multivariable Cox PH regression modelling, we analyzed the (causal) association between detection mode of the primary tumor (FIT screen-detected versus non-screen-detected) and OS after metachronous metastasis while adjusting for potential confounders. RESULTS: Median OS and five-year OS after metachronous metastasis were significantly higher for patients with screen-detected (n = 152) vs. non-screen-detected primary tumors (n = 642): 38.3 vs. 19.2 months, and 35.4% vs. 18.8%, respectively, p < 0.0001). After adjustment for potential confounders, the association between detection mode and OS after metachronous metastasis remained significant (HR 0.70 [95% CI 0.56-0.89]). CONCLUSIONS: Screen-detection of the primary tumor was independently associated with longer OS after metachronous metastasis. This may support the clinical utility of the population screening program and it shows the prognostic value of detection mode of the primary tumor once metachronous metastasis is diagnosed.

Trends in incidence, treatment, and relative survival of colorectal cancer in the Netherlands between 2000 and 2021.

BACKGROUND: The epidemiology of colorectal cancer (CRC) has changed rapidly over the years. The aim of this study was to assess the trends in incidence, treatment, and relative survival (RS) of patients diagnosed with CRC in the Netherlands between 2000 and 2021. PATIENTS AND METHODS: 2 75667 patients diagnosed with CRC between 2000 and 2021 were included from the Netherlands Cancer Registry. Analyses were stratified for disease extent (localised: T1-3N0M0; regional: T4N0M0/T1-4N1-2M0; distant: T1-4N0-2M1) and localisation (colon; rectum). Trends were assessed with joinpoint regression. RESULTS: CRC incidence increased until the mid-2010s but decreased strongly thereafter to rates comparable with the early 2000s. Amongst other trend changes, local excision rates increased for patients with localised colon (2021: 13.6 %) and rectal cancer (2021: 34.9 %). Moreover, primary tumour resection became less common in patients with distant colon (2000-2021: 60.9-12.5 %) or rectal cancer (2000-2021: 47.8-6.9 %), while local treatment of metastases rates increased. Five-year RS improved continuously for localised and regional colon (97.7 % and 72.0 % in 2017, respectively) and rectal cancer (95.2 % and 76.3 % in 2017, respectively). The rate of anti-cancer treatments decreased in distant colon (2010-2021: 80.3 % to 67.2 %; p < 0.001) and rectal cancer (2011-2021: 86.0 % to 77.0 %; p < 0.001). The improvement of five-year RS stagnated for distant colon (2010-2017: 11.2 % to 11.9 %; average percentage of change [APC]: 2.1, 95 % confidence interval [CI]: -7.6, 4.7) and rectal cancer (2009-2017: 12.7 % to 15.6 %; APC: 1.4, 95 % CI: -19.1, 5.5). CONCLUSIONS: Major changes in the incidence and treatment of CRC between 2000 and 2021 were identified and quantified. Five-year RS increased continuously for patients with localised and regional CRC, but stagnated for patients with distant CRC, likely caused by decreased rates of anti-cancer treatment in this group.

Cumulative Incidence, Risk Factors, and Overall Survival of Disease Recurrence after Curative Resection of Stage II-III Colorectal Cancer: A Population-based Study.

Real-world data are necessitated to counsel patients about the risk for recurrent disease after curative treatment of colorectal cancer. This study provided a population-based overview of the epidemiology of recurrent disease in patients with surgically resected stage II/III colorectal cancer.Patients diagnosed with stage II/III primary colorectal cancer between July and December 2015 were selected from the Netherlands Cancer Registry (N = 3,762). Cumulative incidence of recurrent disease was estimated, and multivariable competing risk regression was used to identify risk factors for recurrent disease in patients with primary colon and rectal cancer. Moreover, overall survival (OS) after diagnosis of recurrent colorectal cancer was estimated.Median clinical follow-up was 58 months (Q1-Q3: 22-62). Five-year cumulative incidence of recurrent disease was 21.6% [95% confidence interval (CI): 20.0-23.2] and 30.0% (95% CI: 28.3-33.5) for patients with primary colon and rectal cancer, respectively. Stage III disease and incomplete resection margin in patients with primary colon cancer and extramural vascular invasion in patients with primary rectal cancer were strongly (HR ≥ 2) associated with recurrent disease. Median OS of patients with distant, locoregional, or the synchronous combination of distant and locoregional recurrent disease was 29, 27, and 13 months, respectively (P < 0.001). Patients with distant recurrences limited to liver or lung showed a median OS of 46 and 48 months, respectively. The incidence of recurrent disease was higher in patients with rectal cancer than in patients with colon cancer, predominantly due to higher rates of distant recurrences. OS after recurrent disease was impaired, but subgroups of patients diagnosed with recurrent disease limited to one site showed statistically significantly longer OS. SIGNIFICANCE: Population-based data on recurrent colorectal cancer are rare, but crucial for counseling patients and their physicians. This large nationwide, population-based study provides an up-to-date overview of the epidemiology of recurrent disease in patients with stage II and III primary colon and rectal cancer treated with surgical resection.