Administration of adjuvant chemotherapy in older patients with Stage III colon cancer: an observational study.

AIM: According to established guidelines, patients with Stage III colon cancer should receive adjuvant chemotherapy. However, a significant proportion do not. This study assessed factors associated with the administration of adjuvant chemotherapy and causes of death. METHODS: Patients with Stage III colon cancer who underwent surgery between 2000 and 2009 were selected from two hospitals in the Netherlands. Patient characteristics including comorbidities and treatment preferences, tumour characteristics and follow-up were extracted from the medical records. The patient and tumour characteristics of patients who did receive chemotherapy were compared with those who did not using chi-squared analysis. Differences between the groups in causes of death were recorded together with the duration of follow-up. RESULTS: A total of 348 patients were included. The median age was 73 years (range 33-93). Over half of the patients received adjuvant chemotherapy (50.6%). Patients who did not receive adjuvant chemotherapy were significantly older (P < 0.001), had more comorbidities (P < 0.001) and were more often living alone (P < 0.001). Patients who received no adjuvant chemotherapy had a reduced overall survival, and the cause of death was more often attributed to other causes (60%) than colon cancer (40%). For patients who received chemotherapy, the cause of death was usually attributed to colon cancer (71%). CONCLUSION: Patients who did not receive adjuvant chemotherapy had a worse overall survival and the majority died due to other causes than colon cancer. In our aging society it will become even more important to develop tools to estimate remaining life expectancy in order to improve the selection of older patients for adjuvant treatments.

Effect of preoperative treatment strategies on the outcome of patients with clinical T3, non-metastasized rectal cancer: A comparison between Dutch and Canadian expert centers.

AIM: High-dose-rate brachytherapy (HDRBT) appears to be associated with less treatment-related toxicity compared with external beam radiotherapy in patients with rectal cancer. The present study compared the effect of preoperative treatment strategies on overall survival, cancer-specific deaths, and local recurrences between a Dutch and Canadian expert center with different preoperative treatment strategies. PATIENTS AND METHODS: We included 145 Dutch and 141 Canadian patients with cT3, non-metastasized rectal cancer. All patients from Canada were preoperatively treated with HDRBT. The preoperative treatment strategy for Dutch patients consisted of either no preoperative treatment, short-course radiotherapy, or chemoradiotherapy. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) comparing overall survival. We adjusted for age, cN stage, (y)pT stage, comorbidity, and type of surgery. Primary endpoint was overall survival. Secondary endpoints were cancer-specific deaths and local recurrences. RESULTS: Five-year overall survival was 70.9% (95% CI 62.6%-77.7%) in Dutch patients compared with 86.9% (80.1%-91.6%) in Canadian patients, resulting in an adjusted HR of 0.70 (95% CI 0.39-1.26; p = 0.233). Of 145 Dutch patients, 6.9% (95% CI 2.8%-11.0%) had a local recurrence and 17.9% (95% CI 11.7%-24.2%) patients died of rectal cancer, compared with 4.3% (95% CI 0.9%-7.5%) local recurrences and 10.6% (95% CI 5.5%-15.7%) rectal cancer deaths out of 141 Canadian patients. CONCLUSION: We did not detect statistically significant differences in overall survival between a Dutch and Canadian expert center with different treatment strategies. This finding needs to be further investigated in a randomized controlled trial.

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.

BACKGROUND: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). PATIENTS AND METHODS: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. RESULTS: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). CONCLUSION: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. REGISTRATION NUMBER: Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.

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.

Cause of death the first year after curative colorectal cancer surgery; a prolonged impact of the surgery in elderly colorectal cancer patients.

BACKGROUND: The 1-year mortality after colorectal cancer surgery is high and explains age related differences in colorectal cancer survival. To gain better insight in its etiology, cause of death for these patients was studied. METHODS: All 1924 patients who had a resection for stage I-III colorectal cancer from 2006 to 2008 in the Western region of the Netherlands were identified. Data were merged with cause of death data from the Central Bureau of Statistics Netherlands. To calculate excess mortality as compared to the general population, national data were used. RESULTS: Overall 13.2% of patients died within the first postoperative year. One-year mortality increased with age. It was as high as 43% in elderly patients that underwent emergency surgery. In 75% of patients, death was attributed to the colorectal cancer. In 25% of all patients, registered deaths were attributed to postoperative complications. Elderly patients with comorbidity more frequently died due to complications (p < 0.01). Death of other causes was similar to background mortality according to age group. CONCLUSION: In the presently studied cohort of patients that died within one year of surgery, cause of death was predominantly attributed to colorectal cancer. However, because it is not to be expected that in this cohort the number of deaths from recurrences is very high, the excess 1-year mortality indicates a prolonged impact of the surgery, especially in elderly patients. Therefore, in these patients we should focus on limiting the physiological impact of the surgery and be more involved in the post-hospital period.

Quality assurance in the treatment of colorectal cancer: the EURECCA initiative.

Colorectal cancer is one of the most common cancers in Europe. Over the past few decades, important advances have been made in screening, staging and treatment of colorectal cancer. However, considerable variation between and within European countries remains, which implies that further improvements are possible. The most important remaining question now is: when are we, health care professionals, delivering the best available care to patients with colon or rectal cancer? Currently, quality assurance is a major issue in colorectal cancer care and quality assurance awareness is developing in almost all disciplines involved in the treatment of colorectal cancer patients. Quality assurance has shown to be effective in clinical trials. For example, standardisation and quality control were introduced in the Dutch TME trial and led to marked improvements of local control and survival in rectal cancer patients. Besides, audit structures can also be very effective in monitoring cancer management and national audits showed to further improve outcome in colorectal cancer patients. To reduce the differences between European countries, an international, multidisciplinary, outcome-based quality improvement programme, European Registration of Cancer Care (EURECCA), has been initiated. In the near future, the EURECCA dataset will perform research on subgroups as elderly patients or patients with comorbidities, which are often excluded from trials. For optimal colorectal cancer care, quality assurance in guideline formation and in multidisciplinary team management is also of great importance. The aim of this review was to create greater awareness and to give an overview of quality assurance in the management of colorectal cancer.

An increasing use of defunctioning stomas after low anterior resection for rectal cancer. Is this the way to go?

BACKGROUND: The last decade there has been an increased awareness of the problem of anastomotic leakage after low anterior resection for rectal cancer, which may have led to more defunctioning stomas. In this study, current use of defunctioning stomas was assessed and compared to the use of defunctioning stomas at the time of the TME-trial together with associated outcomes. METHODS: Eligible patients with rectal cancer undergoing low anterior resection were selected from the Dutch Surgical Colorectal Audit (DSCA, n = 988). Similar patients were selected from the TME-trial (n = 891). The percentages of patients with a defunctioning stoma, anastomotic leakage and postoperative mortality rates were studied. Multivariable models were used to study possible confounding on the outcomes. RESULTS: At the time of the TME-trial, 57% of patients received a defunctioning stoma. At the time of the DSCA, 70% of all patients received a defunctioning stoma (p < 0.001). Anastomotic leakage rates were similar (11.4% and 12.1%; p = 0.640). The postoperative mortality rate differed (3.9% in the TME-trial vs. 1.1% in the DSCA; p < 0.001), but was not associated with a more frequent use of a stoma (OR 1.80, 95% CI 0.91-3.58). CONCLUSION: In current surgical practice, 70% of patients undergoing LAR for rectal cancer receives a defunctioning stomas. This percentage seems increased when compared to data from the TME-trial. Clinically relevant anastomotic leakage rates remained similar. Therefore, current routine use of defunctioning stomas should be questioned.

Quality assurance in rectal cancer treatment.

Colorectal cancer is the cancer with the second highest cancer incidence in Europe. Roughly, 1 out of 3 patients with a colorectal malignancy has a rectal carcinoma. Surgery is the cornerstone in the curative treatment of rectal cancer. In the 1980s with conventional surgery, the 5-year local recurrence rate was over 20% and the 5-year overall survival rate around 50%. In the Swedish Rectal Cancer trial, in which 1,168 patients were included, preoperative radiotherapy in addition to conventional surgery resulted in a reduction of more than 50% in the 5-year local recurrence rate in comparison to conventional surgery alone (11 vs. 27%; p < 0.001). In addition, the 5-year overall survival rate improved from 48 to 58% if patients were treated with preoperative radiotherapy in addition to conventional surgery (p = 0.004). With total mesorectal excision (TME), by which the rectum with its mesorectum and visceral fascia are dissected sharply and under direct vision, local recurrence rates dropped and overall survival improved. In the Dutch TME trial, 5 × 5 Gy preoperative radiotherapy in combination with TME surgery was compared to TME surgery alone (1,861 patients). In this trial, the 5-year local recurrence rate for patients treated with TME surgery alone was similar to patients treated in the Swedish Rectal Cancer trial with blunt dissection in combination with preoperative 5 × 5 Gy radiotherapy (11%). If preoperative radiotherapy was added to TME surgery, the 5-year local recurrence rate was reduced to 5.6%. The overall survival rate at 5 years was 64% for both patients treated with TME surgery alone and patients treated with preoperative radiotherapy followed by TME surgery, compared to 48% for patients treated with blunt dissection alone in the previously mentioned Swedish trial. TME surgery is now considered the standard surgical procedure for rectal cancer. However, even if TME surgery is performed, surgical quality varies. First, these results indicate that improvements in the surgical procedure itself can result in major progress regarding long-term oncological outcome, such as decreased local recurrence rates and improved overall survival. Second, it illustrates that variation in surgical quality could lead to large differences in outcome. Recently, it was shown that surgical variation is not only important for patients with rectal cancer, but also plays an important role for the outcome of patients with colon cancer.

Use of aspirin postdiagnosis improves survival for colon cancer patients.

BACKGROUND: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. METHODS: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998-2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. RESULTS: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63-0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50-0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46-0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79-1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70-2.20; P<0.001). CONCLUSION: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of a placebo-controlled trial that investigates the role of aspirin as adjuvant treatment in colon cancer patients.

The EURECCA project: Data items scored by European colorectal cancer audit registries.

AIMS: The EURECCA (European Registration of Cancer Care) consortium is currently formed by nine independently founded national colorectal audit registrations, of which most already run for many years. The cumulative experience of EURECCA's participants could be used to identify a 'core dataset' that covers all important aspects needed for high quality auditing and at the same time lacking needless data items that only consumes administrative effort. The aim of this study is to compare the data items used by the nine registries participating in EURECCA to identify a core dataset and explore options for future research. METHODS: All colorectal outcome registrations participating in the EURECCA project were asked to supply a list with all the data items they score. Items were scored 'present' if they appeared literally in a registration or in case they could be calculated using other items in the same registration. The definition of a 'shared data item' was that at least eight of the nine participating registries scored the item. RESULTS: The number of registered data items varied between 254 (Belgium) and 83 (Norway). Among the 45 variables were patient data, data about preoperative staging, surgical treatment, pre- or postoperative radio- and/or chemotherapy, and follow-up. Items about tumour recurrence or quality of life were scored too little to become shared data items. CONCLUSIONS: A total of 45 items were collected by 8 or more of the participating registries and subsequently met the criteria for a shared data item.

The survival gap between middle-aged and elderly colon cancer patients. Time trends in treatment and survival.

AIMS: For several types of cancer, including colon cancer, the survival gap between middle-aged patients and elderly patients widened between 1988 and 1999 in Europe. The aim of our study was to describe treatments and compare survival rates over time (1991-2005) between middle-aged (<65 years), aged (65-74 years) and elderly (≥ 75 years) colon cancer patients in the mid-western part of the Netherlands to assess whether this survival gap further increased. METHODS: All 8926 patients with invasive colon cancer diagnosed between 1991 and 2005 were selected from the Comprehensive Cancer Centre West. Relative survival was calculated. Relative Excess Risks of death (RER) were estimated using a multivariable generalized linear model with a Poisson distribution. RESULTS: There were no significant changes in the treatment for stage I and II colon. Patients with stage III and IV more often received chemotherapy over time (from 9.6% to 54.3% and from 7.5% to 44.2% for all ages, respectively), while less stage IV patients were operated on (from 73.1% to 55.2%). Relative 5-year survival increased significantly for middle-aged patients (RER = 0.97, 95%CI = 0.95-0.98, p < 0.001), borderline significantly (RER = 0.98, 95%CI = 0.97-0.99, p = 0.05) for elderly patients and not significantly for aged patients (RER = 0.99, 95%CI = 0.97-1.00, p = 0.08) after adjustment for sex, age, grade, stage, and treatment. CONCLUSIONS: The survival gap earlier found by the EUROCARE is confirmed for the mid-western part of the Netherlands, even after adjustment for age, sex, grade, stage and treatment. However, present study does not show an increase in the survival gap between middle-aged and elderly patients.

Importance of the first postoperative year in the prognosis of elderly colorectal cancer patients.

BACKGROUND: Elderly colorectal cancer patients have worse prognosis than younger patients. Age-related survival differences may be cancer or treatment related, but also due to death from other causes. This study aims to compare population-based survival data for young (<65 years), aged (65-74 years), and elderly (≥75 years) colorectal cancer patients. METHODS: All patients operated for stage I-III colorectal cancer between 1991 and 2005 in the western region of The Netherlands were included. Crude survival, relative survival, and conditional relative survival curves, under the condition of surviving 1 year, were made for colon and rectal cancer patients separately. Furthermore, 30-day, 1-year, and 1-year excess mortality data were compared. RESULTS: A total of 9,397 stage I-III colorectal cancer patients were included in this study. Crude survival curves showed clear survival differences between the age groups. These age-related differences were less prominent in relative survival and disappeared in conditional relative survival (CRS). Only in stage III disease did elderly patients have worse CRS than young patients. Furthermore, significant age-related differences in 30-day and 1-year excess mortality were found. Thirty-day mortality vastly underestimated 1-year mortality for all age groups. CONCLUSIONS: Elderly colorectal cancer patients who survive the first year have the same cancer-related survival as younger patients. Therefore, decreased survival in the elderly is mainly due to differences in early mortality. Treatment of elderly colorectal cancer patients should focus on perioperative care and the first postoperative year.