Introduction
Article Outline
This is a very important issue of Seminars in Colon and Rectal Surgery, since it represents a synopsis of some major advances in the field of colorectal cancer that are not at all surgical, yet are crucial for the practicing surgeon to know and to understand. Cytotoxic chemotherapy, targeted antibodies, better understanding of patient and tumor genetic characteristics, and the broader use of systemic therapy in general have radically changed our approach to this disease over the past decade, and this issue is intended to keep the surgeon current on what happens to the patient outside the operating room. When compared with practices of the 1990s, these advances have more than doubled expected median survivals for patients with metastatic colorectal cancer and have led to at least a 25% improvement in disease-free survival following resection. The orchestration of the timing and selection of multiple possibilities of various combinations of drugs and techniques makes the medical oncologist more than the purveyor of palliative 5-fluorouracil we were in the past; this makes the concept of multidisciplinary care throughout the long-term management of the patient with colorectal cancer more vital than ever.
Even the concept of “long-term management” of these patients is a radical departure from historical ways of thinking about colorectal cancer. It is not uncommon now for patients with metastatic disease to be looking for third-, fourth-, even fifth-line chemotherapy options. This was simply not possible in the past, but with current supportive and symptomatic care, and multiple possible combinations of available drugs (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, capecitabine, bevacizumab, cetuximab, panitumumab, even mitomycin—you do the math!), there is almost always another chance for these patients.
The last time Seminars ran an issue with this emphasis was 6 years ago, under Dr. Margaret Kemeny's direction in December 2002. Many of the shifts in therapies I alluded to were beginning to be addressed at that point, but our understanding of what we are doing and why it works has grown tremendously. Surgery of course remains the key to any curative option for these patients, but it is frequently insufficient on its own. In this issue, Dr. Benson addresses how we should use adjuvant therapy to eradicate some of the micrometastases that remain behind after resection in lymph node negative and positive tumors, respectively. Dr. Willett explains combined chemotherapy and radiation therapy for rectal cancer, and Dr. Ryan discusses options for patients with resectable hepatic metastases. For patients with widespread disease, Dr. Clark reviews the multiplicity of agents we can use and how the appropriate combinations can significantly prolong survival; for those with unresectable liver-predominant disease, I discuss various minimally invasive palliative procedures. Drs. McLeod and Kim write about genetic and molecular explanations of how patients and cancers might respond differently to the same agents, while Dr. Lichtman explains how all this relates to the elderly patient. Finally, Dr. Wong tells us how much this all is going to cost financially.
I believe this last point—monetary costs of treatments, the financial impact of our treatment recommendations on both patient and society—is crucial to our responsibility as physicians. This has broad implications both nationally, as we spend an ever-growing proportion of our dollars on health care, and internationally, where many of these agents or treatment modalities are prohibitively expensive, and therefore, unavailable. It is unclear whether or not our health care economy is a “zero-sum” system, and whether (eventually) money for cancer care might have to come at the expense of, say, cardiac rehabilitation or prenatal vitamins. Our new drugs and machines are a tremendous boon for our patients, and we want them available at any cost for our own individual patient. What happens though when the patient cannot afford the copay or is uninsured? What will happen when the country cannot afford this?
Interest and study of colorectal cancer has exploded over the past 15 years: a quick, nonscientific search of “colorectal cancer” in PubMed shows 2620 articles in 1990, and 7166 in 2007 (Fig. 1). (That is 20 articles published every day—are you keeping up?) This growth corresponds to our improved ability to treat the disease, and especially, to the introduction of new drugs and techniques. Colon cancer is big business now. The pharmaceutical industry increased its interest in supporting clinical trials in proportion to development and introduction of new drugs. Marketing and potential profitability have focused R&D money on colon cancer; at the same time, it is the prospect of helping people while realizing tremendous profit that has afforded us clinicians each of these great new drugs. Help and hope are available for our patients to a degree they never were before, but this is a direct result—and a proximal cause—of an enormous economic movement.
Figure 1.
Annual number of published journal articles about colorectal cancer.
Based on (again) simplistic estimates of my own (and Dr. Schrag's 2004 estimates of common drug costs1), if we treat everyone in this country the way we say we should, that would be about 30,000 patients annually with FOLFOX, at a cost of $36,000 each for 6 months; 50,000 patients with metastatic disease using FOLFIRI-B for 10 months, $105,000 apiece; and 30,000 with irinotecan and cetuximab second-line for $62,000 for 4 months. This adds up to about $8.2 billion each year for colorectal cancer; 2004 Medicare cancer drug expenditure for all cancers was $5.3 billion. At some point, our society is going to notice this discrepancy, and decisions will be forced on us. As the ones who write the orders, we physicians need to think about this, before we are asked to justify our fiscal profligacy. We are accountable to each of our patients and need to provide the best care individually possible, but we are at the same time responsible to society as a whole for how we spend money that is not ours and that may in fact not even exist in the future. Our progress against this disease is real and substantial, but still incremental and increasingly expensive. Can we afford this forever?
However, before we have to answer any of these questions, we have the luxury of choosing among many good and helpful options for our patients. The surgeon is frequently the beginning of the patient's odyssey through the cancer care system and needs to know both the promise and the cost of patient choices. Now that we can do so many things, we are starting to learn how to limit the treatments to patients most likely to be helped. For instance, cetuximab is most likely to be active in tumors with wild-type K-RAS, or liver lesions larger than 5 cm will not be eradicated with radiofrequency ablation, or a patient's genetic makeup might preclude the efficacy of a given drug. As we learn more about these parameters, we can start to focus our expensive treatments better in patients whom they will most likely benefit.
Therefore, the present is a very good time for those of us interested in improving the lives of patients with colorectal cancer, and the future will be even better. There are many new decision points in the treatment algorithms for these patients, and the possibilities will continue to grow. We need to know all the options and discover both new ways to go and why the old ones work in a given individual, so that we can select the best course for our patients. This issue is intended to help guide that process.
Reference
PII: S1043-1489(08)00051-1
doi:10.1053/j.scrs.2008.09.001
© 2008 Elsevier Inc. All rights reserved.
