Number of words: 994

Bailar and Smith published their article in May 1986—and it shook the world of oncology by its roots. Even the moderately pessimistic Cairns had expected at least a small decrease in cancerrelated mortality over time. Bailar and Smith found that even Cairns had been overgenerous: between 1962 and 1985, cancer-related deaths had increased by 8.7 percent. That increase reflected many factors—most potently, an increase in smoking rates in the 1950s that had resulted in an increase in lung cancer.

One thing was frightfully obvious: cancer mortality was not declining in the United States. There is “no evidence,” Bailar and Smith wrote darkly, “that some thirty-five years of intense and growing efforts to improve the treatment of cancer have had much overall effect on the most fundamental

measure of clinical outcome—death.” They continued, “We are losing the war against cancer notwithstanding progress against several uncommon forms of the disease [such as childhood leukemia and Hodgkin’s disease], improvements in palliation and extension of productive years of life. . . . Some thirty-five years of intense effort focused largely on improving treatment must be judged a qualified failure.”

That phrase, “qualified failure,” with its mincing academic ring, was deliberately chosen. In using it, Bailar was declaring his own war—against the cancer establishment, against the NCI, against a billion-dollar cancer-treatment industry. One reporter described him as “a thorn in the side of the National Cancer Institute.” Doctors railed against Bailar’s analysis, describing him as a naysayer, a hector, a nihilist, a defeatist, a crank.

Predictably, a torrent of responses appeared in medical journals. One camp of critics contended that the Bailar-Smith analysis appeared dismal not because cancer treatment was ineffective, but because it was not being implemented aggressively enough. Delivering chemotherapy, these critics argued, was a vastly more complex process than Bailar and Smith had surmised—so complex that even most oncologists often blanched at the prospect of full-dose therapy. As evidence, they pointed to a survey from 1985 that had estimated that only one-third of cancer doctors were using the most effective combination regimen for breast cancer. “I estimate that 10,000 lives could be saved by the early aggressive use of polychemotherapy in breast cancer, as compared with the negligible number of lives, perhaps several thousand, now being saved,” one prominent critic wrote.

In principle, this might have been correct. As the ’85 survey suggested, many doctors were indeed underdosing chemotherapy—at least by the standards advocated by most oncologists, or even by the NCI. But the obverse idea—that maximizing chemotherapy would maximize gains in survival—was also untested. For some forms of cancer (some subtypes of breast cancer, for instance) increasing the intensity of dosage would eventually result in increasing efficacy. But for a vast majority of cancers, more intensive regimens of standard chemotherapeutic drugs did not necessarily mean more survival. “Hit hard and hit early,” a dogma borrowed from the NCI’s experience with childhood leukemia, was not going to be a general solution to all forms of cancer.

A more nuanced critique of Bailar and Smith came, unsurprisingly, from Lester Breslow, the UCLA epidemiologist. Breslow reasoned that while age-adjusted mortality was one method of appraising the War on Cancer, it was by no means the only measure of progress or failure. In fact, by highlighting only one measure, Bailar and Smith had created a fallacy of their own: they had oversimplified the measure of progress. “The problem with reliance on a single measure of progress,” Breslow wrote, “is that the impression conveyed can vary dramatically when the measure is changed.”

To illustrate his point, Breslow proposed an alternative metric. If chemotherapy cured a five-yearold child of ALL, he argued, then it saved a full sixty-five years of potential life (given an overall life expectancy of about seventy). In contrast, the chemotherapeutic cure in a sixty-five-year-old man contributed only five additional years given a life expectancy of seventy. But Bailar and Smith’s chosen metric—age-adjusted mortality—could not detect any difference in the two cases. A young woman cured of lymphoma, with fifty additional years of life, was judged by the same metric as an elderly woman cured of breast cancer, who might succumb to some other cause of death in the next year. If “years of life saved” was used as a measure of progress on cancer, then the numbers turned far more palatable. Now, instead of losing the War on Cancer, it appeared that we were winning it.

Breslow, pointedly, wasn’t recommending one form of calculus over another; his point was to show that measurement itself was subjective. “Our purpose in making these calculations,” he wrote, “is to indicate how sensitive one’s conclusions are to the choice of measure. In 1980, cancer was

responsible for 1.824 million lost years of potential life in the United States to age 65. If, however, the cancer mortality rates of 1950 had prevailed, 2.093 million years of potential life would have been lost.”

The measurement of illness, Breslow was arguing, is an inherently subjective activity: it inevitably ends up being a measure of ourselves. Objective decisions come to rest on normative ones. Cairns or Bailar could tell us how many absolute lives were being saved or lost by cancer therapeutics. But to decide whether the investment in cancer research was “worth it,” one needed to start by questioning the notion of “worth” itself: was the life extension of a five-year-old “worth” more than the life extension of a sixty-year-old? Even Bailar and Smith’s “most fundamental measure of clinical outcome”—death—was far from fundamental. Death (or at least the social meaning of death) could be counted and recounted with other gauges, often resulting in vastly different conclusions. The appraisal of diseases depends, Breslow argued, on our self-appraisal. Society and illness often encounter each other in parallel mirrors, each holding up a Rorschach test for the other.

Excerpted from pages 231-233 of ‘The Emperor of All Maladies: A biography of Cancer’ by Siddharth Mukherjee