BIG PROBLEM, BIG BUSINESS, BIG HYPE

First, some basic facts to convey the scale of the problem. Cancer is the second most lethal disease in the U.S., behind only heart disease. More than 1.7 million Americans were diagnosed with cancer in 2018, and more than 600,000 died. Over 15 million Americans cancer survivors are alive today. Almost four out of ten people will be diagnosed in their lifetime, according to the National Cancer Institute.

Cancer has spawned a huge industrial complex involving government agencies, pharmaceutical and biomedical firms, hospitals and clinics, universities, professional societies, nonprofit foundations and media. The costs of cancer care have surged 40 percent in the last decade, from $125 billion in 2010 to $175 billion in 2020 (projected).

Research funding has also surged. The budget of the National Cancer Institute, a federal agency founded in 1937, now totals over $6 billion/year. That is a fraction of the total spent on research by nonprofit foundations ($6 billion a year, according to 2019 study), private firms and other government agencies. Total research spending since Richard Nixon declared a “war on cancer” in 1971 exceeds a quarter trillion dollars, according to a 2016 estimate.

Cancer-industry boosters claim that investments in research, testing and treatment have led to “incredible progress” and millions of “cancer deaths averted,” as the homepage of the American Cancer Society, a nonprofit that receives money from biomedical firms, puts it. A 2016 study found that cancer experts and the media often describe new treatments with terms such as “breakthrough,” “game changer,” “miracle,” “cure,” “home run,” “revolutionary,” “transformative,” “life saver,” “groundbreaking” and “marvel.”

There are more than 1,200 accredited cancer centers in the U.S. They spent $173 million on television and magazine ads directed at the public in 2014, according to a 2018 study, and 43 of the 48 top spenders “deceptively promot[ed] atypical patient experiences through the use of powerful testimonials.” A 2014 study concluded that cancer centers “frequently promote cancer therapy with emotional appeals that evoke hope and fear while rarely providing information about risks, benefits, costs, or insurance availability.”

LITTLE NET PROGRESS AFTER 90 YEARS, BESIDES ANTI-SMOKING EFFORTS

What’s the reality behind the hype? “No one is winning the war on cancer,” Azra Raza, an oncologist at Columbia, asserts in her 2019 book The First Cell: And the Costs of Pursuing Cancer to the Last. Claims of progress are “mostly hype, the same rhetoric from the same self-important voices for the past half century.” Trials have yielded improved treatments for childhood cancers and specific cancers of the blood, bone-marrow and lymph systems, Raza notes. But these successes, which involve uncommon cancers, are exceptions among a “litany of failures.”

The best way to measure progress against cancer is to look at mortality rates, the number of people who succumb to cancer per unit of population per year. The risk of cancer grows with age. (Although childhood cancer gets a lot of attention, Americans under 20 years old account for less than 0.3 percent of all U.S. cancer deaths.) Hence as the average life span of a population grows (because of advances against heart and respiratory disorders, infectious disease and so on), so does the cancer mortality rate. To calculate mortality trends over time, therefore, researchers adjust for the aging of the population.

With this adjustment—which, keep in mind, presents cancer medicine in a more favorable light–mortality rates have declined almost 30 percent since 1991. This trend, according to cancer-industry boosters, shows that investments in research, tests and treatments have paid off. What boosters often fail to mention is that recent declines in cancer mortality follow at least 60 years of increases. The current age-adjusted mortality rate for all cancers in the U.S., 152.4 deaths per 100,000 people, is just under what it was in 1930, according to a recent analysis.

The rise and fall of cancer deaths track the rise and fall of smoking, with a lag of a couple of decades. Cigarette consumption in the U.S. more than doubled between 1930 and the early 1970s and has fallen steadily since then, according to the nonprofit site Our World in Data. Smoking raises the risk of many cancers but especially of lung cancer, which is by far the biggest killer, accounting for more deaths than colon, breast and prostate cancer combined.

Over the past two decades lung-cancer mortality has dropped, but it still remains higher than it was in the 1960s, especially among women, according to Our World in Data. A 2006 analysis concluded that without reductions in smoking “there would have been virtually no reduction in overall cancer mortality in either men or women since the early 1990s.”

NEW TREATMENTS YIELD SMALL BENEFITS, BIG COSTS

Research has linked cancer to many internal and external factors, notably oncogenes, hormones, viruses, carcinogens (such as those in cigarettes) and random cellular replication errors, or “bad luck.” But with the notable exception of the smoking/cancer link, which led to effective anti-smoking measures, that knowledge has not translated into significantly improved preventive measures or treatments. Clinical cancer trials “have the highest failure rate compared with other therapeutic areas,” according to a 2012 paper.

Pharmaceutical companies keep bringing new drugs to market. But one study found that 72 new anticancer drugs approved by the FDA between 2004 and 2014 prolonged survival for an average of 2.1 months. A 2017 report concluded that “most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points,” including survival and quality of life. The authors worried that “the FDA may be approving many costly, toxic drugs that do not improve overall survival.”

Costs of cancer treatments have vastly outpaced inflation, and new drugs are estimated to cost on average more than $100,000/year. Patients end up bearing a significant proportion of costs. More than 40 percent of people diagnosed with cancer lose their life savings within 2 years, according to one estimate.

Immune therapies, which seek to stimulate immune responses to cancer, have generated enormous excitement. Two researchers won the 2018 Nobel Prize for work related to immune therapies, and a new book, The Breakthrough: Immunotherapy and the Race to Cure Cancer, claims that they represent a “revolutionary discovery in our understanding of cancer and how to beat it.”

According to a 2018 report in Stat News, drugs firms aggressively market immune therapies, and patients are “pushing hard to try them, even when there is little to no evidence the drugs will work for their particular cancer.” A 2017 analysis by oncologists Nathan Gay and Vinay Prasad estimated that fewer than 10 percent of cancer patients can benefit from immune therapies, and that is a “best-case scenario.”

Immune therapies trigger severe side effects, and they are also extremely expensive, costing hundreds of thousands of dollars a year, oncologist Siddhartha Mukherjee, author of The Emperor of All Maladies, a bestselling history of cancer, reported in the New Yorker last year. “Subsequent hospital stays and supportive care can drive the total costs to a million dollars or more,” he writes. “If widely prescribed, immune therapies “could bankrupt the American health-care system.”

TESTS LEAD TO OVERDIAGNOSIS AND OVERTREATMENT

The cancer industry, aided by celebrities who claim that tests saved their lives, has convinced the public that screening for cancer is beneficial. The earlier we can detect cancerous cells, the more likely it is that treatment will succeed. Right? Wrong. One of the most significant findings of the past decade is that many people have cancerous or pre-cancerous cells that, if left untreated, would never have compromised their health. Autopsies have revealed that many people who die of unrelated causes harbor cancerous tissue.

Tests cannot reliably distinguish between harmful and harmless cancers. As a result, widespread testing has led to widespread overdiagnosis, the flagging of non-harmful cancerous cells. Overdiagnosis leads in turn to unnecessary chemotherapy, radiation and surgery. Gilbert Welch, a physician whose 2011 book Overdiagnosed: Making People Sick in Pursuit of Health helped bring overdiagnosis to light, recently called it “an unfortunate side effect of our irrational exuberance for early detection.” Overdiagnosis is more insidious than false positives, when tests erroneously indicate the presence of cancer. Biopsies can overturn false positives but not overdiagnoses.

Mammograms and prostate-specific antigen (PSA) tests have led to especially high rates of overdiagnosis and overtreatment for breast and prostate cancer. A 2013 meta-analysis by the Cochrane Collaboration, an international association of experts that assesses medical procedures, estimated that if 2,000 women have mammograms over a period of 10 years, one woman’s life will be saved by a positive diagnosis. Meanwhile 10 healthy women will be treated unnecessarily, and more than 200 “will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.”

Another nonprofit medical group, theNNT.com, has spelled out a disturbing implication of these data. (NNT stands for “number needed to treat,” which refers to the number of people who must receive a treatment for one person to receive any benefit. Ideally, the number is 1.) The NNT notes that some overdiagnosed women might “die due to aggressive therapies such as chemotherapy and major surgery.” Thus any benefit from screening “is balanced out by mortal harms from overdiagnosis and false-positives.” Breast-cancer specialist Michael Baum, who helped found the United Kingdom’s breast-screening program, has advocated abandoning such programs, which he believes might cut short more lives than they extend.

As for PSA tests, a federal task force of medical experts estimates that 1.3 deaths may be averted for every 1,000 men between the ages of 55 and 69 tested for 13 years. But for every man whose life is extended, many more will experience “false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction.” A 2017 analysis by the task force estimated the ratio of beneficial PSA tests to false positives and overdiagnosis to be as high as 1/240.

A 2013 meta-analysis by Cochrane Group found “no significant reduction” in mortality resulting from PSA tests. “The strategy of routinely screening all men with PSA tests leads to interventions that are not saving lives and may be causing harm,” the NNT stated. The discoverer of the prostate-specific antigen, pathologist Richard Ablin, has called the PSA test a “profit-driven public health disaster.”

ALL-CAUSE VERSUS SPECIFIC MORTALITY AND “TORTURING THE DATA”

Studies of tests for a specific cancer generally look at mortality attributed to that cancer. Mammograms are thus deemed effective if women who get mammograms die less often from breast cancer than women who do not get mammograms. This method can overstate the benefits of tests, because it might omit deaths resulting, directly or indirectly, from the diagnosis. After all, surgery, chemotherapy and radiation can have devastating iatrogenic effects, including heart disease, opportunistic infections, other forms of cancer and suicide.

Therefore some studies measure “all-cause” mortality.  A 2015 meta-analysis by epidemiologist John Ioannidis (renowned for bringing the scientific replication crisis to light) and others found no reductions in all-cause mortality from tests for cancer of the breast, prostate, colon, lung, cervix, mouth or ovaries for asymptomatic patients.

In a recent editorial in the European Journal of Clinical Investigation, Ioannidis and four co-authors argue that cancer screening (especially mammograms and PSA tests) does more harm than good and should be abandoned. They expect this proposal to be met with “fierce opposition.” Screening they note, “is big business: more screening means more patients, more clinical revenue to diagnostic and clinical departments, and more survivors in need of care and follow‐up.”

Cancer boosters commonly point to improvements in survival rates, the length of time between diagnosis and death. Survival rates for some cancers have indeed grown as a result of more widespread and higher-resolution testing, which detects cancer earlier. But as a 2015 analysis points out, in general people do not live longer as a result of early detection. They simply live longer with a diagnosis of cancer, with all its harmful emotional, economic and physiological consequences.

Using survival rates to promote tests is an example of what critics of mammography have called “tortur[ing] the data to make it confess to what one knows to be the real truth.” What the data on screening actually suggest is that millions of men and women have endured the trauma of cancer diagnoses and treatments unnecessarily. That strikes me as a case of monstrous malpractice.

CORRUPTION IN THE CANCER INDUSTRY

The aggressive, can-do American approach to health care isn’t working when it comes to medicine in general and cancer medicine in particular. The U.S. spends far more per capita on health care, including cancer care, than any other country, but higher expenditures have not led to longer lives. Quite the contrary. Europe, which spends much less on cancer care than the U.S., has lower cancer mortality rates, according to a 2015 study. So do countries such as Mexico, Italy and Brazil, according to Our World in Data.

The American approach fosters corruption. According to a 2019 essay in Stat News by oncologist Vinay Prasad, many cancer specialists accept payments from firms whose drugs they prescribe. This practice “leads us to celebrate marginal drugs as if they were game-changers,” Prasad argues. “It leads experts to ignore or downplay flaws and deficits in cancer clinical trials. It keeps doctors silent about the crushing price of cancer medicines.”

Last year The New York Times and ProPublica reported that top officials at Sloan Kettering Cancer Center “repeatedly violated policies on financial conflicts of interest, fostering a culture in which profits appeared to take precedence over research and patient care.” Sloan Kettering’s chief medical officer, Jose Baselga, “failed to disclose millions of dollars in payments from drug and health care companies in dozens of articles in medical journals.” Baselga left Sloan Kettering to become head of cancer research at the drug firm AstraZeneca.

The desire of oncologists to produce monetizable findings might also compromise the quality of their research. A 2012 examination of 53 “landmark” cancer studies found that only six could be reproduced. The so-called Reproducibility Project: Cancer Biology has examined 14 more recent highly cited studies, and has confirmed only five without qualification.

SOLUTION: GENTLE CANCER MEDICINE?

So what’s the solution to all these problems? Some health-care experts espouse “conservative medicine” as a way to reduce health-care costs and improve outcomes. In “The Case for Being a Medical Conservative,” a manifesto published last year, four physicians (including the aforementioned Vinay Prasad) urge colleagues to recognize the human body’s “inherent healing properties” and to acknowledge “how little effect the clinician has on outcomes.” Physicians will thus protect themselves “against our greatest foe—hubris.”

Medical conservatives happily adopt new therapies “when the benefit is clear and the evidence strong and unbiased,” the authors emphasize, but many alleged advances “offer, at best, marginal benefits.” Conservative cancer medicine, as I envision it, would engage in less testing, treatment, fear-mongering, military-style rhetoric and hype. It would recognize the limits of medicine, and it would honor the Hippocratic oath: First, do no harm.

Physicians cannot bring about a shift toward conservative cancer medicine on their own. We consumers must help them. We must recognize the limits of medicine and the healing capacities of our bodies. We must resist tests and treatments that have marginal benefits, at best. We may never cure cancer, which stems from the collision of our complex biology with entropy, the tendency of all systems toward disorder. But if we can curtail our fear and greed, our cancer care will surely improve.

A final note: I’d like to thank experts I’ve cited above—John Ioannidis, Siddhartha Mukherjee, Vinay Prasad, Azra Raza and Gilbert Welch—as well as Cochrane and theNNT.com for their blunt, courageous assessments of cancer medicine. People and groups like these represent our best hope for health-care reform. We just have to listen to them.