The outlook for patients with colorectal cancer began to change in the late 1980s when it was first reported that adjuvant radiation therapy after definitive surgery improved survival of patients with stage III rectal cancer. Shortly thereafter, 5-fluorouracil and levamisole were said to decrease recurrence rates and improve survival in patients with stage III (and probably stage II) colon cancer. Since that time, progress has continued more or less steadily with many new active agents identified, novel approaches to the sequence of treatments explored, and recurrence rates and survival continuing to improve. The latest projections have colorectal cancer incidence rates declining by nearly 2% per year and death rates declining by about 4% per year.
Colorectal cancer is common worldwide, particularly in developed countries. Diet has been implicated in its etiology, but no one knows how it influences the development of the disease. Screening for colorectal cancer has proven effective at saving lives, and enormous progress has been made in understanding the progression of mucosal lesions from polyps to invasive cancers. Familial polyposis and nonpolyposis forms of the disease have been identified as well, and molecular causes of the disease defined.
A number of preventions are being tested, some with promising results. A large number of targeted biologics and chemotherapeutic agents have been shown to have activity. Knowledge of basic science has been applied to aid the development of preventions, early diagnosis, and novel treatments.
Indeed, treatment progress has been so rapid over the last few years and the number of tools has burgeoned to the extent that it has become confusing to know what agents in what combination should be used when treating colorectal cancer. It is hoped that this monograph adds some clarity to this evolving area of medicine.
Chua and Cunningham from the Royal Marsden Hospital critically review the area of adjuvant treatment, while de Gramont and his colleagues from Hopital Saint-Antoine in Paris review the data on treatment of advanced colorectal cancer. These outstanding physicians provide the latest data, together with expert commentary, on the major clinical trials in colorectal cancer. Their recommendations are solidly evidence-based as of late 2008. We all hope that additional improvements are in the offing.
Despite the optimism, many feel that the improvements in survival are not happening fast enough. This slow progress in population survival improvement appears largely due to the failure of physicians to use the life-extending therapies on their patients with colorectal cancer. Alfred Neugat and his colleagues at Columbia performed a population-based study that documented the delivery of adjuvant treatment to less than 50% of colorectal cancer patients over age 65 years who could benefit from the therapy. Currently about half of all patients are over age 65 and the percentage is projected to increase to 70% by 2030. By all measures, the elderly receive similar benefits from treatment that do younger people. The bias against treating older patients has got to be addressed systematically so that the benefits of the treatment advances can have their maximal influence on survival. Although a fraction of older patients may have comorbidities that make the delivery of effective doses of therapy more difficult, that fraction is substantially less than 50%. In addition, more progress is required in tests that predict how a particular tumor and a particular patient may respond to treatment.
Colorectal cancer is an example of a common solid tumor in which substantial progress in diagnosis, prevention, early detection, and treatment has begun thanks to the insights gained from basic and clinical research over the last 25 years. It is hoped that the pace of discovery further accelerates and the discoveries are rapidly translated to the benefit of our patients.