Book Review

Colorectal Cancer in Clinical Practice: Prevention, Early Detection and Management

N Engl J Med 2002; 347:71July 4, 2002

Article

Colorectal Cancer in Clinical Practice: Prevention, Early Detection and Management
Edited by Paul Rozen, Graeme P. Young, Bernard Levin, and Stephen J. Spann. 136 pp., illustrated. London, Martin Dunitz, 2002. $49.95. ISBN: 1-901865-87-8

It is an exciting time to be a practitioner in the field of colon and rectal neoplasia. The past decade has brought great progress in our understanding of the environmental and genetic basis of this disease and in our ability to treat it successfully. Armed with new knowledge and effective therapies, we are beginning to see the possibility of preventing or curing most colon and rectal cancers. With that in mind, Colorectal Cancer in Clinical Practice is very timely. It is well written and easy and pleasurable to read, and it should be of great interest to those wishing an update on progress in this rapidly evolving field. Each chapter addresses a key question; the questions address issues ranging from the magnitude of the problem worldwide to the practicality of prevention, screening, and treatment. Written by four professors, three of whom are gastroenterologists and one of whom is a family physician, the book is principally focused on issues of tumorigenesis, prevention, and screening.

Key to the many messages of the book are the genetic and environmental factors involved in tumorigenesis. Although the initial concept of the adenoma–carcinoma sequence dates back to the early 1970s, it was not until 1990 that Vogelstein and colleagues elucidated the molecular basis of the development of colorectal cancer. The authors clearly and concisely describe the many abnormal genes contributing to colorectal cancer and discuss how mutations may be inherited or acquired and how the proteins these abnormal genes produce may affect central regulatory functions or other processes, such as metabolism. For hereditary colon-cancer syndromes, such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, the genetic basis of carcinogenesis can be attributed to the inheritance of mutated forms of regulatory genes — the adenomatous polyposis coli gene and mismatch-repair genes, respectively. In other forms of “familial” colorectal cancer, genetic susceptibility to the cancer may be increased when the genes responsible for the metabolism of carcinogens are altered. In this regard, we are starting to appreciate how genetic alterations may interact with environmental factors and how together they may influence the risk of the development of cancer.

The importance of environmental factors — such as diet, lifestyle, and exposure to carcinogens, as substantiated by epidemiologic studies of migrant populations — is also given proper attention. The role of dietary factors is discussed not only from a theoretical point of view but also in terms of practical approaches to reducing environmental risks and in terms of strategies for future prevention.

Equally impressive work has been performed in the realms of diagnosis and therapy for colon and rectal cancer. The broad acceptance of screening will probably have the greatest impact on the incidence of lower gastrointestinal tract cancers and the associated mortality. Identifying genetic risks and detecting and removing premalignant lesions should be lifesaving. Data from several large studies of fecal occult-blood screening do, in fact, suggest that reductions in the rates of death from colon and rectal cancers may be a reality. This book provides details on several strategies for screening, and the potential risks, benefits, and practical application of each strategy are delicately and objectively discussed. This is no minor feat.

After the discussions of prevention and screening, the book takes us to the other end of the spectrum — that is, to the therapeutic advances that have been made in this field. Although the primary curative therapy remains surgery, the application of multimodal therapy has expanded our ability to achieve meaningful five-year survival rates in patients with colorectal cancer. The adjuvant administration of fluorouracil-based chemotherapy in patients with node-positive colon cancer significantly increases the chance of cure after surgical resection. Similarly, in patients with rectal cancer, the benefit of external-beam radiation therapy before or after surgery in reducing the rate of local recurrence and improving the chance of survival has now been established. Surgical options have also evolved and now include minimally invasive approaches such as laparoscopic colectomy for colon cancer and local excision for early rectal cancer; both of these approaches are under clinical investigation. For more advanced, traditionally fatal forms of cancer such as those involving liver metastases and locally advanced rectal cancer, aggressive surgery can be combined with newer chemotherapeutic agents (irinotecan and oxaliplatin) and intraoperative radiation therapy, respectively, to offer the hope of cure and relief of symptoms. These therapies are effective in selected patients and push research toward new frontiers.

Heidi Nelson, M.D.
Mayo Clinic, Rochester, MN 55905
nelsonh@mayo.edu