Molecular medicine is a rapidly emerging feature in the diagnosis and treatment of disease. Enormous potential benefits for patients are developing, some of which will be truly transformational. Along the way, however, troubling questions must be answered. How will one know when to use newer strategies, and when are the older strategies “good enough”? How will the more expensive diagnostics and therapeutics be paid for in a reimbursement environment that already views medical care as too expensive? How can the legitimate business needs of developers of tests and treatments to make a profit in a capitalist environment be balanced against the legitimate, sometimes conflicting, needs of diagnosticians/clinicians to make a living? In a medical care delivery system that is largely unplanned and disjointed, how can the contributions of scientists, business people, and physicians be coordinated to produce the best possible patient outcomes?
The narrowly focused problem of diagnostic strategies in the workup of cancer of unknown primary (CUP) provides an ideal test case to examine some of these issues. Considerable tension exists between those who champion the use of older immunohistochemistry-based diagnostic strategies and those who promote newer approaches based on tumor gene expression analysis. Many unanswered questions exist regarding the strengths and weaknesses of each approach. A third approach lurks in the background, that of diagnostic nihilism—the idea that CUP remains a grim diagnosis in most cases despite the best therapeutic efforts, so that the quest to determine the site of origin in CUP is largely moot and of only academic interest, and therefore, logically, is not worth pursuing.
When faced with complex dilemmas in the care of patients, it is easy to become confused by distracting issues which, although possibly valid in themselves, can merge into a disorienting confluence. In those situations, it is always useful to step back and simplify. Sweep away all other issues and simply ask, “What is best for the patient?” Even that simple question is complex in itself, but at least it recognizes the primacy of the patient against all other competing interests and personal points of view. The Institute of Medicine has advanced the STEEEP principles.1 These attributes are defined as care that is:
- Safe: avoiding injuries to patients from the care that is intended to help them;
- Timely: reducing waits and sometimes harmful delays for both those who receive and those who give care;
- Effective: providing services based on scientific knowledge to all who could benefit and refraining from providing services to those not likely to benefit (avoiding underuse and overuse, respectively);
- Efficient: avoiding waste, including waste of equipment, supplies, ideas, and energy;
- Equitable: providing care that does not vary in quality because of personal characteristics such as gender, ethnicity, geographic location, and socioeconomic status; and
- Patient-centered: providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions.
These principles serve as an excellent template for examining the use of immunohistochemistry and gene expression analysis in the quest to define the primary site of cancer.
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