Effects of Screening Compliance on Long-term Reductions in All-Cause and Colorectal Cancer Mortality.

BACKGROUND & AIMS: Randomized trials have shown that biennial fecal occult blood test (FOBT) screening reduces mortality from colorectal cancer (CRC), but not overall mortality. Differences in benefit for men vs women, and by age, are unknown. We sought to evaluate long-term reduction in all-cause and CRC-specific mortality in men and women who comply with offered screening, and in different age groups, using individual participant data from 2 large randomized trials of biennial FOBT screening, compared with an intention to treat analysis. METHODS: We updated the CRC and all-cause mortality from the Danish CRC screening trial (n = 61,933) through 30 years of follow up and pooled individual participant data with individual 30-year follow-up data from the Minnesota Colon Cancer Control trial (n = 46,551). We compared the biennial screening groups to usual care (controls) in individuals 50-80 years old using Kaplan Meier estimates of relative risks and risk differences, adjusted for study differences in age, sex, and compliance. RESULTS: Through 30 years of follow up, there were 33,478 (71.9%) and 33,479 (72.2%) total deaths and 1023 (2.2%) and 1146 (2.5%) CRC deaths in the biennial screening (n = 46,553) and control groups (n = 46,358), respectively. Among compliers, biennial FOBT screening significantly reduced CRC mortality by 16% (relative risk [RR], 0.84; 95% CI, 0.74-0.96) and all-cause mortality by 2% (RR, 0.98; 95% CI, 0.97-0.99). Among compliers, the reduction in CRC mortality was larger for men (RR, 0.75; 95% CI, 0.62-0.90) than women (RR, 0.91; 95% CI, 0.75-1.09). The largest reduction in CRC mortality was in compliant men 60-69 years old (RR, 0.59; 95% CI, 0.42-0.81) and women 70 years and older (RR, 0.53; 95% CI, 0.30-0.94). CONCLUSIONS: Long-term CRC mortality outcomes of screening among compliers using biennial FOBT are sustained, with a statistically significant reduction in all-cause mortality. The reduction in CRC mortality is greater in men than women-the benefit in women lags that of men by about 10 years.

Population screening for colorectal cancer: advantages and drawbacks.

Screening for colorectal cancer (CRC) has been shown to reduce mortality from the disease as well as incidence. Several methods for screening are available, but none are ideal. The present short review discusses the advantages and drawbacks using fecal occult blood tests (FOBTs), fecal DNA tests, flexible sigmoidoscopy (FS), colonoscopy, double contrast barium enema, and computed tomographic colonoscopy. The use of FOBTs with following colonoscopy in persons with a positive test has been shown to reduce mortality as well as the incidence of CRC in several randomized trials. It is likely that other methods will do the same, but it is not clear how large the benefit will be. Repeated testing is necessary for FOBTs and DNA tests as well as FS, and a high degree of acceptability is crucial for the effectivity of all tests in a national program. National services may be subject to variations in enthusiasm and expertise, resulting in varying acceptability and number of complications. It is recommended to perform pilot studies in limited populations (as in the UK) before embarking on a screening program on a national level.

Influence of long-term colonoscopic surveillance on incidence of colorectal cancer and death from the disease in patients with precursors (adenomas).

Case-control studies and short term prospective studies have suggested that selected groups of patients with precursors of colorectal cancer may benefit from colonoscopic surveillance after initial removal of adenomas. The aim of the present study was to demonstrate such a possible benefit from long term (1-24 years) colonoscopic surveillance in a population of patients with all types of adenomas regardless of size and way of removal. Two thousand and forty-one patients with a first time diagnosis of colorectal adenoma were included in prospective surveillance between year 1978 and 2002. All adenomas were considered. Incidence of CRC and mortality from CRC was calculated, using age, sex, and calendar specific number of person years of follow-up for comparison with the standard Danish population. CRC was found in 27 patients, the expected number being 41 (RR 0.65, 95% CI 0.43-0.95). Three of the 27 patients died from CRC, the expected number being 25 (RR 0.12, 95% CI 0.03-0.36). A total of 6 289 colonoscopies resulted in severe complications in 20 patients and two died from complications. Long-term colonoscopic surveillance may reduce incidence of CRC as well as mortality in patients with sporadic adenomas. The benefit is reduced to a minor degree by complications from surveillance.

[New treatment strategies for patients with primary non-resectable rectal cancer]. / Ny behandlingsstrategi for patienter med primaer, ikkeresektabel rectumcancer.

INTRODUCTION: Patients with locally advanced rectal cancer (LARC) have a poor prognosis. Preoperative radiotherapy may shrink the tumour and make subsequent resection possible. The use of modern principles of preoperative radiotherapy in combination with chemotherapy and an active surgical attitude increases the chance for radical surgery and cure. MATERIALS AND METHODS: A single-institution, prospective evaluation of a new treatment strategy in patients with LARC was done. RESULTS: From 1998 to 2000, 20 patients with LARC were treated with high-dose radiochemotherapy (60 Gy and chemotherapy, UFT/leucovorin), and resectability was evaluated four to six weeks after termination of radiochemotherapy. Sixty percent of the patients subsequently had microscopic radical surgery. CONCLUSION: Patients with LARC should preferably be treated with high-dose preoperative radiotherapy in combination with chemotherapy. Evaluation of resectability should be performed at least four weeks after termination of radiotherapy. This strategy, in combination with modern surgical techniques, increases the probability of success of radical surgery and cure.

Three randomized long-term surveillance trials in patients with sporadic colorectal adenomas.

OBJECTIVE: Guidelines for surveillance of patients with previous sporadic colorectal adenomas are based on retrospective long-term follow-up and prospective short-term studies. The aim of the present studies was to compare relative risk (RR) of new neoplasia as well as complications, using different intervals between examinations in long-term surveillance. MATERIAL AND METHODS: Between l98l and l991, patients with pedunculated and small, flat and sessile adenomas were allocated at random to a 24 months (group A) or 48 months (group B) interval between surveillance colonoscopies (n=671). Patients with flat and sessile adenomas greater than 5 mm in diameter were randomized to intervals of 6 months (group C) or 12 months (group D) between l981 and 1987 (n=73). Finally, 200 patients with similar adenomas as in groups C and D were randomized to 12 months (group E) or 24 months (group F) from 1988 to 2000. The study ended in 2002. RESULTS: Advanced adenomas were equally as frequent in group A and group B, but colorectal cancer (CRC) was found significantly more often in group B (RR = 6.2 (1.0-117.4)). Severe complications occurred in 4 patients in group A and 2 patients in group B. Advanced new adenomas tended to be more frequent in group D than in C (p=0.08), but only one CRC was detected and this was in group C. There was no significant difference in the risk of CRC between the E and F groups, but the two cancers in group E were both early stage, in contrast to those in group F. Severe complications were seen in one patient in group E and also in group F. CONCLUSIONS: The results suggest that 2-year intervals should be used between colonoscopies in patients with previous pedunculated adenomas and small, flat and sessile adenomas, whereas larger, flat and sessile adenomas may need intervals of 1 year.

[Future perspectives in screening for colorectal cancer]. / Fremtidsperspektiver i screening for kolorektal cancer.

Based on international experience, pilot studies with fecal occult blood tests and colonoscopy in those with blood in the stools are now to be performed in Scandinavia in limited geographic areas before introducing countrywide screening. The Danish State has offered to pay for feasibility studies in two counties. Provided that the results of randomised clinical trials are reproduced according to acceptability and stage of the cancer found and the organisation is feasible, it will then be possible to evaluate newer technologies as well as other methods which have not previously been evaluated in a satisfactory way.

Lifestyle and 30-day complications to surgery for colorectal cancer.

This study aimed to identify lifestyle factors with impact on 30-day mortality and complications after surgery for a first time colorectal adenocarcinoma. All patients in Denmark within a 20 month period were registered in a nationwide database; 57% were included in the analysis. Logistic regression was used, adjusted for age, sex and disease- or treatment related factors. BMI=30 kg/m2 increased the risk of complications in general (CIG), impaired wound healing (IWH), deep wound infection and mortality. Smoking increased the risk of CIG, IWH and mortality. Alcohol increased the risk of IWH and anastomotic leakage. Self perceived physical fitness at or below average increased the risk of CIG, thrombosis, and mortality. The population attributable risk was 23% for complications and 64% for mortality. The results suggest that lifestyle factors are important for the course of the 30-day postoperative period. Lifestyle factors should be considered in future prediction models for outcome after colorectal cancer surgery.

Screening for colorectal cancer.

Colorectal cancer (CRC) is the most common cancer in the Nordic countries after breast and prostate cancer. About 15,000 new cancers are diagnosed and more than 7000 patients will die from CRC in 2005. CRC fulfils most of the criteria for applying screening; the natural history is well known compared with many other cancers. CRC may be cured by detection at an early stage and even prevented by removal of possible precursors like adenomas. Faecal occult blood test is the only CRC screening modality that has been subjected to adequately sized randomised controlled trials (RCT) with long-term follow-up results, using Hemoccult-II. Sensitivity for strictly asymptomatic CRC is less than 30% for a single screening round, but programme sensitivity has been estimated to be more. Biennial screening with un-rehydrated Hemoccult-II slides has shown a CRC mortality reduction of 15-18% after approximately 10 years of follow-up in those targeted for screening. For those attending, the mortality reduction has been estimated at 23%. Denmark has decided to do feasibility studies to try to evaluate whether a population-based screening run by the community will have the same effect as has been demonstrated in the randomised trials. In Norway the government has accepted no formal population-based screening. In Finland, the Ministry of Social Affairs and Health made a recommendation in 2003 to the municipalities to run a randomised feasibility study with FOBT screening for colorectal cancer as a public health policy that is repeated every second year. In 2004 the first municipalities started. It has been claimed that today Sweden cannot afford CRC screening despite the potential mortality benefit. There is sufficient evidence for the efficacy of screening for colorectal cancer with fecal occult blood test every second year. There is, however, only little evidence on the effectiveness of screening when run as a public health service and there is insufficient knowledge of harmful effects and costs, even in RCTs.

Plasma TIMP-1 in patients with colorectal adenomas: a prospective study.

Colorectal cancer patients have increased plasma levels of tissue inhibitor of metalloproteinases-1 (TIMP-1). However, it remains unresolved whether colorectal adenomas are associated with increased plasma TIMP-1. Plasma TIMP-1 levels were determined using an immunoassay in 121 patients prospectively enrolled from surveillance colonoscopy programmes. TIMP-1 levels were correlated to various clinicopathological parameters. No significant associations were found between plasma TIMP-1 and size, macro- or microscopic morphology or grade of dysplasia of the adenomas. No significant differences in TIMP-1 levels were found between patients with adenomas (n = 36), hyperplastic polyps (n = 12) or no pathology (n = 68) of the large intestine. However, patients with colonic (n = 3) or rectal (n = 2) adenocarcinomas had significantly increased TIMP-1 levels (P = 0.02). The present study demonstrates that measurement of plasma TIMP-1 cannot be used for the identification of adenomatous or hyperplastic polyps of the large intestine.