Review article
The Advanced Adenoma as the Primary Target of Screening

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The Adenoma-Carcinoma Sequence

The relationship of colorectal cancer to a premalignant neoplastic lesion was demonstrated in cross-sectional studies by Lockhart-Mummery and Dukes19 at St. Marks Hospital in the United Kingdom and reported in the 1920s. This relationship was further delineated by Muto et al,24 and later termed the polyp-cancer sequence by Morson.23 This concept was challenged by Castelman and Krikstein8 because they failed to find adenomatous tissue associated with many colorectal cancers. It was subsequently

The Validity of the Adenoma as a Surrogate Marker of Colorectal Cancer Risk

Adenomas have a prevalence of 30% to 50% in autopsy studies in Western countries, increase as a function of age, and are more common in men than women.38 A very small percentage, perhaps as few as 1%, grow to a size of 1 cm or more and some transform into cancer. The presence of a single small rectosigmoid adenoma, particularly with tubular pathology and no high-grade dyplasia, does not seem to confer an increased risk of colon cancer according to a study reported by Atkin et al.4 On the other

The Validity of the Advanced Adenoma as a Surrogate Marker of Colorectal Cancer Risk

The advanced adenoma is a more valid surrogate biologic marker for colorectal cancer risk than are smaller adenomas because it is the advanced adenoma that has the greater potential to develop into a cancer. In studies by Atkin et al4 and Bertario et al6 advanced adenomas seem to confer an increased risk of subsequent colorectal cancer. Furthermore, in the National Polyp Study cohort, the colorectal cancer incidence reduction reported by Winawer et al40, 41 was associated with removal of

Use of Adenomas as Surrogate Markers in Clinical Trials

Although the adenoma endpoint has been used in the past, various studies have increasingly used the advanced adenomas as a more valid endpoint in intervention studies. In the National Polyp Study, a high proportion of patients had adenomas at follow-up surveillance colonoscopies after clearing the colon of all identifiable polyps. The proportion of patients who had advanced adenomas at follow-up, however, was small; 3.3% at the 3-year follow-up and 6% at the 6-year follow-up.41, 43 The authors

Concluding Comments

There is now a better understanding of the progressive pathologic stages of the adenoma-carcinoma sequence. A review of available evidence strongly suggests that the advanced adenoma is the most valid surrogate marker for present and future colorectal cancer risk. Based on this understanding the advanced adenoma should be used in the evaluation of new screening technology, nutritional interventions, and chemoprevention agents. Prevention studies should demonstrate a high efficacy in reducing

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