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

doi:10.1016/j.ejso.2014.09.011

European Journal of Surgical Oncology (EJSO)

Volume 40, Issue 12, December 2014, Pages 1789-1796

https://doi.org/10.1016/j.ejso.2014.09.011 Get rights and content

Abstract

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.

Introduction

Several studies have shown remarkable differences in colorectal cancer survival across Europe.1, 2 For rectal cancer, five-year relative survival in the period 2000–2007 ranged from 38.8% to 59.9% between European nations.³ The variation in outcome could be explained by case mix variation, differences in socioeconomic status and variation in registration. More importantly, many countries have their own guidelines resulting in variation in treatment plans. Different treatment strategies may lead to differences in survival.4, 5, 6 Currently it is unknown which country has a better treatment strategy compared with the other countries.

In the last two decades clinical audits have been initiated in several European countries to improve the outcome of rectal cancer patients. A clinical audit is a quality instrument that collects detailed clinical data from different health care providers, which can be adjusted for baseline risk and subsequently fed back to individual hospitals and doctors. The European rectal cancer audits have not only successfully identified best practice and underperforming hospitals, but also achieved amongst others, a rise in survival, nationally.7, 8, 9 However, variation in outcome between the European countries remains.¹⁰ The EUropean REgistration of Cancer CAre (EURECCA) project was initiated by the European CanCer Organisation (ECCO) in order to decrease these differences and to improve cancer care through Europe.10, 11 This project has the aim to generate the best care for all cancer patients by combining national audit structures.

Most of the previous studies concerning European survival differences lacked information about stage of disease and treatment strategies within countries and therefore, results should be interpreted with caution. The present study was undertaken to compare preoperative treatment of rectal cancer patients including the differences in tumour stage between five European countries participating in the EURECCA-project: Norway, Sweden, Denmark, Belgium, and the Netherlands.

Section snippets

Patients

Patients diagnosed with rectal cancer in 2008 and 2009 were extracted from the Norwegian Colorectal Cancer Registry (NO), the Swedish Colorectal Cancer Registry (SE), the Danish Colorectal Cancer Group database (DK), Project on Cancer of the Rectum [PROCARE] of the Belgian Cancer Registry (BE) and the Netherlands Cancer Registry (NL). All registrations include roughly the entire national population except for the Belgian procare registration that represented <50% of the Belgian rectal cancer

Characteristics

A total of 16,401 patients diagnosed with rectal cancer in 2008 and 2009 have been identified in the five clinical cancer registries. The median age of the patients was 67 years in NL, 70 years in SE, 70 years in DK, 70 years in NO, and 69 years in BE. About 20% of the patients from each country did not receive a resection of the tumour (NL 20.1%, SE 17.0%, DK 24.6%, NO 20.8%, and BE 17.0%). Non-resected patients were slightly older than the complete group; 71 years in NL, 75 years in SE, 75

Discussion

Remarkable findings in this study were the large differences between the countries in the proportion of patients receiving preoperative radiotherapy or chemoradiation. Relative survival at 1 year was significantly better for patients from SE as compared to NL. However, Sweden has no automated link of death certificates to the cancer registration, which could result in some missed cases of death. When stratified for age groups, the differences in relative survival were only present in the

Strengths and limitations

Several limitations are present in this study. Unknown is to what extent the differences in patient characteristics are due stage migration, variation in case-mix or differences in data registration. In the case of NL, patients are defined with a clinical unknown stage when no MRI is available. DK did not register preoperative (clinical) TNM stage, and neither collected information about stage 0 postoperatively (γpT0). But since DK had a relatively low administration of preoperative treatment,

Conclusions

A large variation in administration of preoperative treatment has been found between NO, SE, DK, BE, and NL. After adjustment for age, gender, and stage, Sweden had a significant better relative survival for patients aged ≥75 years at 1 year compared to the Netherlands. The differences in 1 year relative survival are expected to be caused by differences in peri-operative care, selection of patients, and fitness of elderly patients. By comparing these items between the countries, which will be a

Funding

This study was funded by European CanCer Organisation (ECCO), European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO), and European Society of Medical Oncology (ESMO). There has been no role of the sponsors in the study design, in the collection, analysis, and interpretation of data, in writing the manuscript, or in the decision to submit the manuscript for publication.

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Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established.
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Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established.
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A more recent report demonstrated low risk rectal cancers can be identified with use of high-quality MRI and safely treated without neoadjuvant treatment [30]. Furthermore, the use of neoadjuvant radiotherapy in the Netherlands was much higher compared to other countries with a similar local recurrence rate [31]. As a result, the guideline was revised in 2014 recommending a more restrictive use of radiotherapy.
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.
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.
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.
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.
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These benefits must be weighed against undesired side effects [6]. The EURECCA consortium compared the rates of preoperative treatment for rectal cancer among five different European countries between 2008 and 2009, and found significant variation, ranging between 28% and 86% [18]. The highest rates were found in the Nederland.
Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons.
This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II.
Out of 14,391 patients,8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%,p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers.
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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.
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.
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).
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Since the TME trial, the standard treatment of primary resectable rectal cancer in the Netherlands became SCRT with immediate surgery (SCRT-IS), and CRT was reserved for downstaging of the more advanced rectal cancers. Based on the population-based studies provided by the Dutch ColoRectal Audit (DCRA), a high use of RT was demonstrated compared to other European countries [7,8]. The high use of preoperative RT was one of the important topics initiating the revision of the Dutch colorectal cancer guideline in 2012.
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.
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.
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.
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.

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^l: Both authors contributed equaly to the manuscript.

^m: On behalf of the Norwegian Colorectal Cancer Project.

ⁿ: On behalf of the Swedish ColoRectal Cancer Registry.

^o: On behalf of the Danish Colorectal Cancer Group database.

^p: On behalf of the Belgian Project On Cancer Of The Rectum (PROCARE).

^q: On behalf of the Study group for Therapies Of Rectal Malignancies (STORM).

^r: The members of the EURECCA consortium are given in the Appendix section.

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

Abstract

Introduction

Section snippets

Patients

Characteristics

Discussion

Strengths and limitations

Conclusions

Funding

Lancet Oncol

Eur J Surg Oncol

Eur J Surg Oncol

Comput Programs Biomed

Eur J Cancer

Lancet Oncol

Eur J Cancer

Eur J Cancer

Patterns of care for European colorectal cancer patients diagnosed 1996–1998: a EUROCARE high resolution study

Acta Oncol

A population-based comparison of the survival of patients with colorectal cancer in England, Norway and Sweden between 1996 and 2004

Gut

Survival differences between European and US patients with colorectal cancer: role of stage at diagnosis and surgery

Gut

Understanding variations in survival for colorectal cancer in Europe: a EUROCARE high resolution study

Gut

Cancer survival in England and the influence of early diagnosis: what can we learn from recent EUROCARE results?

Br J Cancer

The Swedish rectal cancer registry

Br J Surg