Christopher Booth walks into the examination room with a warm smile, pulls up a chair close to his patient, and leans in. He doesn’t check notes on a clipboard, doesn’t glance at a computer screen. He studies his charts thoroughly before entering so that patients have his full attention. Booth, a medical oncologist and professor at Queen’s University in Kingston, Ontario, specializes in gastrointestinal cancer. Most of the people he treats have advanced disease. In this Friday-morning clinic, he will see nine patients, most with complex cases.
A woman in her twenties who’d had colorectal cancer is frightened about a node on her lung. Booth assures her it’s just something to watch. An elderly man’s colon cancer has come back. It’s potentially curable, but the new tumour is in such a difficult place that removing it will require massive, risky surgery. It will be best to shrink the tumour first with chemotherapy. Another gentleman with relapsed metastatic colon cancer is here with his wife. They understand his disease is not curable, but they’re concerned the headaches he’s experiencing might mean it is escalating. They want to travel. A seventy-one-year-old woman, otherwise healthy, has pancreatic cancer. Booth must give her the disappointing news that she isn’t eligible for a clinical trial where she could have chemotherapy ahead of surgery. Her liver tests indicate it would be dangerous. Without diminishing the gravity of her situation, he offers reasons to be positive and promises that she will get the drug after the surgery.
These are tough conversations. Booth believes it’s important to be honest, pragmatic, and upfront with patients, but he is also kind, listens, takes his time. He asks how they are emotionally, extends a comforting touch. For the woman with pancreatic cancer, his office will arrange a social worker. To the young woman anxious about the node on her lung, he suggests an app for mindful meditation, one he’s tried himself.
Booth loves being a cancer doctor. He knew from the moment he began his oncology rotation in residence twenty years ago it was what he’d choose to do. He was drawn to the “powerful human relationships” between oncologist and patient. Beyond the mechanics of knowing which drug to use or which test to order and how to interpret the results, oncology is about balancing hope and reality, he explains. It’s about providing patients with information to make decisions about their own care.
Booth’s second passion is research. He sees patients two days a week. The other three, he leads a team that delves into “really big picture issues”: how the health care system works, how care is delivered, and to what extent patients benefit from treatments. He is the Canada research chair in population cancer care and director of cancer care and epidemiology at Queen’s Cancer Research Institute. He is deeply concerned about a cancer system he says is in serious trouble. He sees resources squandered on “obscenely” costly new cancer drugs that do not improve survival, while resources for basic services like palliative care are lacking. He is calling for a common-sense revolution in oncology.
He’s pushing back against a cancer theology that goes back five decades to December 23, 1971, the day that United States president Richard Nixon signed the National Cancer Act and launched the “war on cancer,” pledging hundreds of millions of dollars for research. If it was possible to send a man to the moon, lobbyists had argued, why not put the same kind of money and skill toward trying to conquer cancer in five years, in time for the nation’s 200th birthday, in 1976? Nixon’s National Cancer Act reverberated globally. The National Cancer Institute is now the world’s largest cancer research funder, sponsoring cutting-edge research that goes beyond American borders. Canadian scientists have enjoyed a long-standing collaboration with their US counterparts and are the only non-American partner in the NCI’s clinical trials network. Canada joined the war and embraced the rhetoric of cure.
Today, the sums of money devoted to cancer research are staggering. The value of the NCI’s annual research grants, which totalled $67.3 million (US) in 1972, approached $3 billion in 2020. Members of the International Cancer Research Partnership—an alliance of more than 140 cancer research organizations in the US, Canada, Europe, Japan, and Australia—accounted for $8.5 billion (US) for research in 2018. In Canada, funding from government and charities amounted to $7.4 billion over the fifteen years from 2005 to 2019, an average of roughly $500 million a year. None of this includes investments by industry.
And what has the chase for the cure accomplished? In Canada, cancer diagnosis rates have declined slightly each year over the past decade, by 1.2 percent for women and 1.5 percent for men. Cancer mortality rates are also down. In 1984, the mortality rate for men was 335 per 100,000. By 2021, it decreased to 217. Similarly, the mortality rate for women decreased from 204 per 100,000 to 163. The improvements are attributed to early detection, better treatments, and fewer people smoking.
So yes, we’ve made progress. Yet cancer remains the leading cause of death. About one in two Canadians will be diagnosed with cancer in their lifetimes; one in four will die of it. The toll is more than 80,000 per year. The proportion of the population dying from cancer has actually grown in comparison to other causes of death in recent years. In 2019, cancer accounted for 28.2 percent of all deaths, while heart disease accounted for just 18.5 percent. And even though the rates of diagnosis and mortality have declined, the number of cases will increase as the population grows and ages.
And this is where Booth would like to begin a conversation. As a society facing an increasing burden of cancer, costing an estimated $26 billion in 2021, how do we allocate resources? Should we continue spending $150,000, or more, a year to treat a patient with a drug that provides marginal benefits? Booth acknowledges that, in the past decade, we’ve had some transformative medications. However, he says, these are exceptions floating in a sea of mediocre drugs that extend life for three months on average, often just weeks. There would be greater public health benefit if we instead put more into end-of-life care. He says it’s easy to give a drug but almost impossible to find resources to let patients stay in their homes with good nursing, companionship, and good food. “We completely fail patients near the end of life where we provide one thing but not the other,” he says. “How can we be okay with that?”
The premise behind the war on cancer was wrong. Cancer is not a single grim foe. We know now there are hundreds of distinct cancers. An oncologist in the 1980s would have known there were two types of lung cancer. Today, by looking at the molecular biology of the tumour cells, scientists can determine there are at least eighty different subtypes of lung cancer. There are at least twenty subtypes of breast cancer. In Booth’s speciality, there was just colon cancer until the past decade. Now there are a dozen known subtypes.
Cancer is the result of errors and mutations in our genetic code. Human cells are constantly replenished through the process of cell division, and normally, each new cell contains a copy of our entire genome. But mistakes occur. A gene might not get copied. There might be multiple copies of the same gene. Bits of chromosomes can fuse together. The errors can be random, or they can result from DNA damage caused by exposures to harmful substances, such as ultraviolet rays from the sun. The result is rogue cells—cancer cells—that divide and grow in ways they shouldn’t, forming tumours and invading different parts of the body. And this is what makes cancer so hard to solve: my cancer may look like yours—it might develop in the same place, say, the colon—but each person’s cancer has a unique set of genetic changes. The variation and complexity in tumour biology make treatment a challenge.
Not to say that we can’t cure some cancers in some people or at least help people live longer. Today, thanks to treatments like tamoxifen, only a small minority diagnosed with breast cancer will die of it. Due to early detection and better treatments, most will not die of their colon cancer. Many cancers caught early can be cured with surgery and radiation, often without additional drug treatment. However, for most types of cancers, once they have become metastatic—they’ve spread from their original site to other parts of the body—there is no cure. Even so, people are surviving some metastatic cancers longer. Twenty-five years ago, survival for men with metastatic prostate cancer was two years on average; now, with more effective treatments, it’s about five.
Other cancers continue to stymie our efforts: esophageal, ovarian, and some lung cancers, for example, or glioblastoma, a brain cancer. Cancers in which symptoms don’t show up until the disease has already advanced, and for which there are no screening procedures, are the hardest to treat. Pancreatic cancer is especially difficult. By the time it’s discovered, it has usually spread to the liver or blood vessels and cannot be removed by surgery except in 10 to 20 percent of cases. The average prognosis at the metastatic stage is about a year. Although pancreatic cancer accounts for about 3 percent of cancers diagnosed annually in Canada, it is the third leading cause of cancer deaths.
For decades, the best treatment available, after surgery and radiation, was chemotherapy. It’s a blunt tool that ravages the good cells along with the bad and can cause as much suffering as the disease. But today’s powerful microscopes increasingly reveal the intricacies of a human cell: how DNA, RNA, and proteins interact and alter in ways that permit cancer cells to grow—and how, with technology, those processes might be stopped.
One evolving option is immunotherapy. Normally, our immune system detects and kills abnormal cells. But cancer cells can trick our immune cells by sending a signal that says, “Do not attack.” In the 1990s, scientists discovered it’s possible to shut off that signal. That led to the development of drugs called immune checkpoint inhibitors, which block the signal’s pathway. The first such drug was approved by the US Food and Drug Administration in 2011, for treating advanced melanoma. By 2017, the FDA had approved this type of immunotherapy for about a dozen different metastatic cancers, including advanced kidney cancer, and Hodgkin’s lymphoma. For metastatic melanoma, immunotherapy has proved exceptional, giving years of life to many. In other cancers, however, a small minority of people do very well on the drugs, but most do not. Either they do not respond at all or suffer intolerable side effects. Researchers have yet to find biomarkers to predict who will, or won’t, do well.
A newer immunotherapy innovation is chimeric antigen receptor T-cell therapy, or CAR-T, which involves modifying a patient’s immune system cells. The cells are taken from a patient’s blood and then re-engineered in a lab to form attack cells that are infused, in large numbers, back into the patient. A highly personalized treatment for certain blood cancers such as leukemia or lymphoma, CAR-T is often a last-ditch chance for people who have not seen results from other treatments, or when other treatments no longer work. The FDA approved the first such therapy in 2017. Health Canada approved it in 2018. There is enthusiasm for this new technology, because where there was once no hope, some patients are surviving three to five years. As yet, CAR-T is not a treatment for solid tumour cancers, meaning cancers in organs or tissues.
One drawback of CAR-T is that it works only in about 30 to 40 percent of cases. Also, it’s extremely expensive. The list price of a single CAR-T treatment is $500,000 (US). A Canadian initiative is attempting to address the cost issue. Scientists from the Ottawa Hospital, BC Cancer, and Vancouver General Hospital have developed a publicly funded non-commercial product costing about $100,000. Ottawa haematologist Natasha Kekre is currently leading a clinical trial testing the product on a small group of lymphoma patients. In early results, half of the patients responded to the treatment. A big part of her goal, Kekre says, “is not just treating patients and curing them but also to do this in a way that is feasible and sustainable.”
Another major innovation is targeted therapy, or drugs that avoid damaging normal cells by zeroing in on cancer cells directly. They block the signals that cause cancer cells to grow, or they change the proteins within cancer cells to make them die. The first such drug was Herceptin, approved by the FDA in 1998. Herceptin targets a specific protein implicated in one type of breast cancer. Gleevec, approved by the FDA in 2001, was revolutionary in the treatment of chronic myelogenous leukemia. CML patients have a chromosomal aberration where pieces from two chromosomes swap places. Researchers discovered the culprit genes responsible for this fusion produced a mutant protein. Gleevec worked to inhibit that protein. Before Gleevec, CML was a fatal disease. Today, most CML patients can expect an almost normal lifespan. Building on Gleevec’s success, the majority of new oncology medicines developed in the past two decades are targeted therapies for a long list of cancers.
Going one step further, we have precision oncology. Precision medicine, sometimes called personalized medicine, uses someone’s genetic information to find a drug that might work for them. With cancer, the genetic information is taken from a tumour. Janessa Laskin is a medical oncologist and associate professor of medicine at the University of British Columbia. In 2012, she co-founded, and now co-leads, the BC Personalized Onco-Genomics Program, known as POG. The program sequences DNA and RNA in cancer cells to determine whether a person’s cancer is “actionable,” meaning there is a genetic aberration that can be targeted. A team of researchers then scours the literature, looking for drugs that could block what’s causing the aberration. It’s not always about fancy new drugs; they also try old drugs or drugs approved for another disease or another type of cancer they could use off label.
Laskin’s view is that there might be thousands of distinct cancers. “I do think that every cancer is unique,” she says. That doesn’t mean we need a different treatment for each individual person. “But the more we know about cancers and the different things that can drive dysregulated growth, the more we see how different things are.” So far, POG has sequenced the tumours of about a thousand people with incurable disease. Not surprisingly, extension of life for most has been a matter of months, with rare, remarkable exceptions. Laskin explains that the value of the program lies in the data that will give us a better picture of how different cancers behave and clues to better treatments.
Ian Tannock is not so sure precision oncology can be effective. He is a medical oncologist and biophysicist, retired from a celebrated thirty-six-year career at the Princess Margaret Cancer Centre in Toronto. He reflects that, after the triumph of Gleevec and advances in gene sequencing, oncologists might have believed tumours could be genetically sequenced in order to attack specific mutations on an individualized basis. “Disappointingly, that hasn’t happened,” he says. Researchers in France were the first to test precision oncology in a randomized clinical trial. They compared a group of patients whose tumours were sequenced and who were treated with off-label drugs to a group under traditional care. In 2015, they reported that precision medicine made no difference. More trials are currently underway in France and the US. In 2021, Tannock looked at 22,000 patients in several such trials and found that the percentage of people who could be matched to a drug based on a genetic profiling of their tumours was low, and that, for many, the drugs didn’t work. At best, precision medicine remains a work in progress.
Tannock says a major problem is that cancers change as they grow. A 2012 study in The New England Journal of Medicine showed that you can have biopsy tumours from different places in the body, or even from different parts of the tumour, and find varying genetic mutations. “You can think of a tumour as a tree having different-coloured leaves, and targeting one or two of these will prune the tree but it won’t make the tree stop growing.” He believes people are being hoodwinked into thinking that genetic testing of cancer cells is going to be the answer.
Whether it’s immunotherapy, precision oncology, the latest buzz around a cancer vaccine, or blood tests to screen for cancer, new technology spurs renewed fervour for a cure. Booth recognizes there have been significant advances, but he cringes at the hype from the pharmaceutical industry and from media reports that make new drugs or innovations look like breakthroughs. They feed false hope to patients. He sees it in his practice. Many who are told their cancers likely won’t come back, and that additional treatment is probably unnecessary, regardless feel they should give themselves the opportunity to do everything possible. They insist on the treatment. Or when he’s made it clear the disease is incurable, patients in their last few months of life think that to not fight it would be giving in. They may have family and friends who urge them to keep trying, sometimes influenced by something they’ve read or seen on TV.
Rachel Koven’s husband, Ken, was in Booth’s care before he died of metastatic gastroesophageal cancer seven years ago, at the age of forty-eight. After an initial round of chemotherapy, he did well for nine months, then the disease spread to his brain. What followed was a very difficult period when he had full brain radiation, which did not help much, and then insisted on additional treatment, which resulted in an acute infection. Yet he wanted that treatment again. He refused to contemplate palliative care. Koven did her best to respect and support her husband’s wishes but regrets that he missed out on any quality of life at the end of their time together. “It would have been much more peaceful and less traumatic if he would have accepted the place he was in,” she says. “And we would have managed things more gently in the end.”
In a way, the language of war puts pressure on patients to keep fighting, partly based on a misplaced faith in drugs. Many of the drugs developed in the past twenty years provide marginal benefit to people with incurable disease. Drug regulators like the FDA, Health Canada, and the European Medicines Agency permit shortcuts in the interest of getting drugs to market faster. Drugs can be approved on the basis of what’s called progression-free survival. Did the drug shrink the tumour? And how long was it before it grew again? The assumption is that the interval before the tumour progresses once more can predict how long the patient will actually live. “We measure how long it takes a tumour to grow on a CAT scan, and we assume that translates to people living longer,” Booth explains. It doesn’t.
When manufacturers are allowed shortcuts, it is usually on the condition that they do further trials to confirm a clinical benefit. A review of drugs approved by the FDA between 1992 and 2017 found that only in 20 percent of those further confirmatory trials was there evidence that people lived longer. Health Canada approves most but not all of the drugs the FDA approves. Then, before they get to market, there is an additional layer of scrutiny from the pan-Canadian Oncology Drug Review, created by the provincial and territorial ministries of health to make recommendations on which drugs are both clinically and cost effective. Looking at drugs for solid tumour cancers recommended from 2011 to 2020, Booth’s team found that for only half of seventy-eight such drugs was there evidence that patients lived longer—for an average of just 3.7 months. And this data comes from clinical trials, where patients often do better than those in the real world.
Consider, too, how costly cancer drugs can be. In 2019, Canada spent $3.9 billion on oncology medication. That’s three times the total in 2010. Expensive new drugs for metastatic cancer are driving the ballooning expenditure. In the US, the average annual cost for a new cancer treatment is $196,000 (US). That would be just under $270,000 in Canadian dollars, although drugs are cheaper in Canada due to our drug price review mechanisms and negotiations with manufacturers on behalf of provinces.
If we are striving to help people live longer, the cost could well be justified. But what trade-offs are we willing to accept for drugs that extend life by a matter of weeks? Especially if the quality of life in those remaining weeks is poor due to the harmful side effects from treatment and due to what Booth calls “time toxicity.” When patients are at the end of life, he’d like them to consider how much of their remaining time they will spend getting to and from appointments and sitting in waiting rooms, forgoing time on the boat with the grandkids because they are ill from the treatment or not travelling to a family wedding because it would mean missing a chemo session.
Booth’s research has shown that, for patients in the last year of life, whatever extension is gained may be completely offset by the time used up getting treatment. He encourages oncologists to be open with their patients about minimal benefits so they can better decide how to live their last days. One recent US study reported a high percentage of terminally ill patients did not understand their treatments would not cure them.
In 2016, Bishal Gyawali was a young oncologist from Nepal studying in Japan when he read a news story about a US cancer centre suing a billionaire philanthropist over the right to use the term “cancer moonshot.” How ridiculous, he thought. Who cares who owns it? The term had become a household phrase when then vice president Joe Biden used it to describe a program he had launched earlier that year to support cutting-edge technology that would “end cancer as we know it.” But Gyawali couldn’t imagine the results of moonshot efforts in precision medicine or immunotherapy being available to patients like his in Nepal who couldn’t even afford the old drugs. “Forget the moon,” he wrote in a blog post. “I’d rather support a ‘cancer groundshot’ that focuses on smoking and obesity reduction campaigns, promotes exercise and healthy diet, and encourages research that can be immediately applied to every global community.”
The term caught on. In 2017, Gyawali was invited to speak at an international conference. Booth was excited to hear about it and picked up the phone. He urged Gyawali to write a paper about a “cancer groundshot.” The paper was eventually published in The Lancet Oncology. In 2019, Gyawali passed up a position at Harvard to join Booth at Queen’s, where he is now associate professor of oncology and public health.
Booth and Gyawali hope to convince oncology colleagues, and the public, that the best cancer care isn’t about the latest super-tech innovation. The moonshot approach may lead to better outcomes for some people sometime in the future. Their groundshot approach would be a parallel effort that would improve the quality of life for people coping with illness right now. It would concentrate on treatments that we know work and make access to care more equitable. There are gaps in northern and Indigenous communities, and among poorer and immigrant communities, where people are less likely to be referred to oncology specialists. Booth argues that many across the world currently do not have access to bread-and-butter chemotherapy or basic hormone therapy for breast cancer. “We could save many more lives right now if we just implement the knowledge we already have.”
A cancer groundshot would include an emphasis on prevention. Anti-smoking campaigns have resulted in fewer deaths from lung cancer. The HPV vaccine has the potential to eliminate cervical cancer. Screening has reduced deaths from colon cancer. In 2014, a huge research project conducted by Cancer Epidemiology and Prevention Research at Cancer Care Alberta, in partnership with the Canadian Cancer Society, brought together scientists from across the country to quantify the risks for cancer that we can control. The study, called ComPARe (Canadian Population Attributable Risk of Cancer), resulted in a series of reports published in 2019. The main conclusion: four out of ten cancers are preventable.
According to ComPARe’s analysis of 2015 data, smoking was linked to 17.5 percent of all cases in that year, mostly lung cancers, but also to cancers related to the liver, esophagus, pancreas, bladder, and kidneys. Physical inactivity was linked to almost 4.9 percent of all cancers. Ultraviolet radiation from the sun and tanning beds: 2.3 percent. Other risk factors include alcohol, sedentary behaviour, low fruit and vegetable consumption, red and processed meat. Emerging in the research is the increasing role that excess body weight will play in the future. Unless trends reverse, cancer deaths related to obesity will double to 5,600 deaths per year within the next twenty-five years. In all, the study identified more than twenty modifiable risk factors—behaviours or circumstances we can change—linked to thirty cancer types. The ComPARe findings suggest we can prevent 85 percent of lung cancers, 43 percent of colorectal cancers and 21.4 percent of female breast cancers.
Stunning as the Canadian research may seem, it is consistent with similar work in the US, the UK, and Australia. We could reduce the cancer burden on future generations with greater efforts in prevention. Yet prevention accounts for only 2 to 5 percent of cancer research funding in Canada. In the fifty years of the “war on cancer,” our obsession has been fixing the problem, not stopping it from occurring.
In the 1970s context, the focus on cure is understandable. Today we know how random and complex cancer can be and how difficult it is to achieve progress. Yet simplistic promises persist. Princess Margaret Cancer Foundation’s fundraising slogan claims “together we can conquer cancer in our lifetime.” Tannock hates that slogan intensely. “I think that is lying to patients, and I think it is abhorrent.”