September 15, 2011 17 Comments
In the June 13, 2011, issue of Time magazine, Ruth Davis Konigsberg described cancer patients who refuse to take potentially lifesaving therapy. Her article, titled “The Refuseniks – why some cancer patients reject their doctor’s advice,” examined the rationale applied by patients who decline chemotherapy. Many of these patients are rational, articulate, intelligent and capable individuals. While there are those who by virtue of religious belief, underlying depression, or loss of loved ones, decline interventions, many of these patients make compelling arguments in favor of their decisions.
When we examine the basis of these patients’ therapeutic nihilism, much of it reflects the uncertainty of benefit combined with the certainty of toxicity. What these patients articulate is the fundamental dilemma confronted by cancer patients, what we might describe as their logical assessment of “return on investment.”
Everything in life is based on probabilities. Will your husband or wife be true? Will you have a boy or a girl? Will you live to see retirement? Will your nest egg be adequate? Cancer medicine is no different.
Will the treatment I’m being offered extend my life long enough to be worth the short- and medium-term toxicities that I will certainly suffer?
While I cannot address this question with regard to surgery or radiation, I feel uniquely qualified to do so in the context of chemotherapy. What, after all, is a chemosensitivity assay? When correctly performed, it is a laboratory test that dichotomizes groups of patients with average likelihoods of response (e.g. 20%, 30%, 40%, etc.) into those who are more or less likely to respond based on the results. On average, a patient found sensitive in vitro has a twofold improvement in response, while those found resistant have a demonstrably lower likelihood of benefit. We have now shown this to be true in breast, ovarian, and non-small cell lung cancers, as well as melanoma, childhood and adult leukemias, and other diseases.
To address the misgivings of the Refuseniks, we might ask the following question: Would you take a treatment that provided a 30 percent likelihood of benefit? How about a 40 percent? 50 percent? 60 percent? 70 percent? Or 80 percent? While many might decline the pleasure of chemotherapy at a 20-30 percent response rate, a much larger number would look favorably upon a 70 percent response rate. On the flipside, a patient offered a treatment with a 50 percent likelihood of benefit (on average), who by virtue of a lab study realizes that their true response rate is closer to 19 percent (based on resistance in vitro), might very logically (and defensibly) decline treatment. These real life examples reflect the established performance characteristics of our laboratory tests (Nagourney, RA. Ex vivo programmed cell death and the prediction of response to chemotherapy. Current Treatment Options in Oncology 2006, 7:103-110.).
Rather than bemoan the uncertainties of treatment outcome, shouldn’t we, as clinical oncologists, be addressing these patients’ very real misgivings with data and objective information? I, for one, believe so.