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Why we need a new war on cancer

Advances in screening and diagnosis are sending some cancer patients down aggressive treatment paths that they shouldn't be on.

Sharon Kirkey, National Post, May 4, 2017

A contralateral, prophylactic mastectomy is the most radical operation Dr. Angel Arnaout has ever performed.

It involves making a long incision, from sternum to just beneath the arm, and essentially amputating a perfectly healthy breast in a woman who only has cancer on the opposite side.

After surgery, there's no sensation on the chest wall, just a band of numbness.

Arnaout first performed a "CPM" early in her practice for a woman so terrified her disease-free breast would one day turn cancerous too, "she swore she couldn't live a single day of her life unless I took both of them off."

What wasn't known then but is clear now is that, except for the highest risk women, the procedure offers a minimal to nonexistent survival advantage.

It hardly seems to matter. Rates of contralateral prophylactic mastectomies have increased 82 per cent in Ontario alone over the past three years. In the United States, up to 25 per cent of newly diagnosed breast cancer patients are undergoing the aggressive procedure. A decade ago, fewer than five per cent did.

Many women opting for bilateral mastectomies have been told they have ductal carcinoma in situ, or DCIS, tiny flecks of calcium deposits once virtually unseen before the widespread embrace of organized breast screening programs.

The cells that make up DCIS look like early cancer under a microscope. Doctors assumed finding, and aggressively going after these "precursors" would reduce the rate of invasive, and more lethal, breast tumours. But the massive detection of DCIS - which today accounts for nearly one-quarter of all breast cancers - hasn't been accompanied by a meaningful falloff in the incidence of invasive cancers, suggesting many women diagnosed with DCIS may be undergoing aggressive treatments with minimal to no benefit.

In the war against cancer, we've arrived at a moment: A cancer re-think.

Not only are we unearthing too many cancers that should be left alone, but some "cancer" patients may have conditions that may not be cancer at all, in modern terms.

Nearly half a century after Richard Nixon signed into law what would become known as the "war on cancer," where do we stand?

We are hardly winning the battle.

Yes, survival rates are improving - modestly. Five-year survival rates for all cancers combined have increased to more than 60 per cent, up from 50 per cent in the 1970s. Some of the greatest triumphs have been cancers that strike children. There, survival rates have skyrocketed.

However, too many people are still getting sick and dying from cancer. It has now overtaken heart disease as the leading killer of Canadians, and the number of new diagnoses is projected to increase 40 per cent annually by 2030 as baby boomers age.

Progress has been dazzling for some tumours, slim to none for others. Brutal surgeries of the past have been replaced by less aggressive operations, but treatments for metastatic disease - cancer that has spread to other parts of the body - is seriously lagging, experts say.

Fewer than half of new cancer drugs prolong survival by more than a few months over older drugs.

All of this begs the question: Is there a better way to fight this deadly disease?

In the New War on Cancer, a multi-part series in print and online, the National Post poses this question as we look at the state of the disease, and who is actually getting cancer in Canada. We also examine the business of cancer, and the much-hyped new cancer drugs that often do little to lengthen the lives of patients. We explore how prevention, even living with cancer, offer great promise for the future.

Provocatively, the Post is also exploring how the cancer establishment is coming to grips with overtreatment, and how screening is sending some people down a road of aggressive treatment they should never have been on.

As Otis Brawley, chief medical officer of the American Cancer Society told the Post: "Some of the people we've cured didn't need to be cured."

An ever-growing proportion of the population knows someone who survived a cancer diagnosis. Less clear is how many were never destined to develop symptoms or die from their condition.

"The fastest way to increase five-year survival rates," said Dr. Gilbert Welch, "is to diagnose a whole lot of people with cancer."

Welch, an American academic, cancer researcher and expert in overdiagnosis, said the old medical dictionary definition of cancer is "a neoplastic disease" whose natural outcome is, ultimately, death.

That led to the belief all cancers are bad - that each one begins life as a small tumour that inexorably grows, spreads and kills.

The belief all cancers are deadly started in the 1850s, when German pathologist Rudolph Virchow performed autopsies on women who had died of invasive breast cancer. Some of them had such advanced disease their breasts had been literally eaten away, said Brawley.

"Today, we can find a lesion in a woman's breast the size of a green pea. And we can stick a needle into it and send a piece of that pea-sized lesion to a pathologist. And that pathologist says, 'this thing that you've sent me, this pea-sized lesion, looks just like what the Germans said killed that woman in 1850."

That tiny lesion may be genetically programmed to spread and kill. Alternatively, "It may be programmed to stay pea-sized for the next 50 years in this 50-year-old woman's breast," Brawley said. Or it may run out of its blood supply, shrink and die.

It's not just sophisticated cancer screening that's picking up indolent tumours. The more doctors order ultrasounds, CT scans and MRIs for "non-specific" physical complaints, like pain in the belly, the more we're picking up suspicious lumps and lesions purely by chance - so-called "incidentalomas" that may otherwise never have revealed themselves in the person's lifetime.

"Once in a while, these are serious conditions, and that's when everyone wins," said Dr. Laurence Klotz, a Toronto urologic oncologist who, over the course of two decades, has revolutionized how men with low-risk prostate cancer are treated worldwide.

However, much of the time, incidentalomas may never pose a threat. "But the knee-jerk position has been that if someone is found to have a small cancer, you better treat it before it gets worse," Klotz said.

Overtreatment not only causes harm through the side effects of treatment, it can forever label people as having had "cancer."

The simplest way to determine overdiagnosis and overtreatment is when an increase in diagnoses of a particular cancer occurs, but there's no corresponding drop in the death rate. Last summer, researchers working for the World Health Organization's cancer arm estimated half a million people in a dozen countries, including Canada, had been overdiagnosed with thyroid cancer alone over the last two decades.

Research suggests the magnitude of overdiagnosis ranges from 15 to 25 per cent of breast cancers detected by mammography to as many as 60 per cent of prostate tumours picked up by PSA screening, and 70 per cent of thyroid cancers.

Studies also suggest a substantial proportion of kidney tumours represent overdiagnosis, Welch writes in the Journal of the National Cancer Institute, either because they stop growing, "or they grow too slow for the tumour to cause symptoms before the person dies of something else."

Still, medicine is messy. With no fool-proof way of separating what's "barely" cancer, or a low-risk lesion from those destined to grow and kill, it's a dangerous game to pick and choose.

Researchers are racing to find biological and molecular markers, genomic signatures to better know: These are the cancers worth paying attention to, these are the ones most likely to progress.

"The real problem is the turtles, the cancers that aren't going anywhere," Welch said in an interview. "Unfortunately, screening is really good at finding turtles - it's really good at find the quiescent cancers that are just below the surface, the ones that are not obvious to people clinically, but if you look hard, all of a sudden you recognize they're there.

"If we could perfectly distinguish between all these things, there wouldn't be a problem. You'd recognize, that's a turtle and we're not going to do anything about it.

"But we can't and that's why doctors tend to treat everything they find that's labeled 'cancer.' "

For patients, the gut reaction is often the same: Whatever it is, get it out. Fear, fuelled by well-meaning awareness campaigns, has made us rightfully paranoid about cancer.

When she first meets with her breast cancer patients, the first question Arnaout of The Ottawa Hospital gets is, "Am I going to live or die?"

"As breast oncologists or cancer specialists we've spent the last decade trying to reduce the morbidity of what we do to patients - in other words, trying to reduce the harm of what we do to patients, while achieving maximal cure," said Arnaout. That includes smaller and less aggressive surgeries, less chemotherapy and radiation. "But at the same time, we're finding that, because of their fear and anxiety, patients are going the opposite way. They're demanding bigger things, bigger surgeries.

"It's not uncommon to hear women say, 'I don't care about my breasts. Or, I want to undergo chemotherapy.' And when your response is, 'you don't need to do that,' what I often get back is, 'I have three kids. I want to know I did everything possible,'" Arnaout said.

"It's very hard to try to convince people that doing more is not helpful. In fact, it's harmful."

For example, chemotherapy and radiation to the chest can damage the heart or lungs, or cause long-term side effects to the brain, spinal cord or nerves. As many as 20 to 30 percent of women who undergo mastectomy experience post-mastectomy pain syndrome - lingering nerve pain that causes burning, tingling and stabbing pain at the surgery site.

"I see what happens to people who end up on the wrong side of this, and behind each of these overdiagnoses is a story of a person who suffers because of it," said breast surgeon Dr. Laura Esserman, at University of California, San Francisco

When mammography began detecting DCIS, people thought, "My god, this is a precursor of cancer, let's just get rid of them all and we're going to be preventing invasive cancer and curing it," she said.

"Great idea. Except it didn't happen." After a decade of taking out 60,000 cases a year of DCIS in the U.S. alone, the incidence of invasive breast cancer hasn't fallen.

The problem is DCIS absolutely tortures women. "I feel like Alice in Wonderland who has fallen down the rabbit hole," one woman diagnosed with a two-centimetre DCIS wrote recently on an online cancer forum. Esserman knows of women who were warned they would almost certainly lose their breast to cancer if they didn't agree to surgery. Women "are afraid to do stuff and not do stuff and very few people are open to the idea to do less," she said. "But it's starting to change."

With DCIS, the abnormal cells are confined to the lining of the milk ducts. If the cells don't penetrate that basement membrane, by definition, there can be no chance of the cancer spreading, says Dr. Geoff Porter, a surgical oncologist and professor of surgery at Dalhousie University in Halifax.

However, 'There are some patients who, if left untreated, over time it eventually will turn into invasive cancer. The problem is we also know that, 40 to 60 per cent of patients with DCIS, that DCIS will never change if left untreated."

There are some hints at distinguishing the good from the bad, including the size of the tumour and the woman's age (Research led by Dr. Steven Narod, of Toronto's Women's College Hospital, suggests younger women diagnosed before age 35, and black women, are at higher risk.)

Esserman, who has begun to offer carefully selected women with low-grade DCIS the option of hormone therapy, or monitoring with regular ultrasounds, uses a genomic test to estimate the woman's chances her DCIS will recur, or turn into invasive cancer, over the next 10 years.

This strategy of active surveillance was first employed for prostate cancer, thanks largely to Klotz, who found that after the enthusiastic adoption of prostate-specific antigen (PSA) screening, "we were diagnosing lots of patients with small amounts of cancer." However, it was obvious to him not all these men were really at risk. Most had low PSA, while those with advanced disease had higher levels. "So we said, let's just monitor; the ones who go up rapidly, we'll treat."

Initially, the approach created a firestorm. "People thought, this was dangerous; that we didn't care if patients died," Klotz said. "But we were absolutely convinced we were on the right track."

Today, active surveillance for low-risk prostate cancer is the cornerstone of treatment in cancer clinics around the globe. Crucially, a pivotal study published last September in the New England Journal of Medicine confirmed Klotz's gut instinct: men with early stage prostate cancer who opt for monitoring have the same risk of dying of prostate cancer over the next 10 years - one per cent - as those who opt for more aggressive surgery or radiation.

Still, while the use of active surveillance is growing in Canada, an estimated 1,500 Canadian men with low-risk prostate cancer received treatment in 2013, according to the Canadian Partnership Against Cancer. Many likely could have been spared treatment and the attendant side effects, such as impotence and urinary incontinence requiring pads or diapers.

A study published in 2015 by Narod and his colleagues found a low rate of cancer death - 3.3 per cent at 20 years - among women treated for DCIS. Importantly, more aggressive therapy - lumpectomy plus radiation - didn't improve survival over surgery alone.

Narod said some cases of DCIS should be considered "de facto" breast cancers. "Whatever it is, it has a three per cent chance of becoming fatal," he said. "If it's not cancer, why do three per cent of patients die?"

Esserman says no one is doing things to intentionally cause harm. But she says DCIS shouldn't be treated as an emergency, and that women should be given time and options, including, if appropriate, active surveillance.

"People will blame you and say, 'What are you doing? It's wrong, it's crazy,' " she says.

"If our treatments had no consequences, no negative side effects, I wouldn't be pushing so hard for change. But people don't love what we offer for treatments."

For now, fundamentally, it comes down to this: How much of a risk are people prepared to take?

Most women seek the surgery for peace of mind. They think, "I don't want to go through this again." Others feel having both breasts removed and reconstructed will leave them with better symmetry. Both "new" breasts will look more the same.

But a bilateral mastectomy doubles the risks of complications. There is also a not-insignificant risk of chronic pain. "I've definitely seen cases where it makes you wonder whether it was truly worth it," Arnout says.

Today, if a woman asks to have a normal, disease-free breast removed, Arnaout stalls for time. She schedules multiple visits and, except for high-risk cases, never offers it until at least a year out.

Meanwhile, Welch and others are calling for a serious re-thinking of thresholds for what's labelled "abnormal" and when to intervene. He believes it may be better to simply ignore the tiniest abnormalities and stop looking so hard for early forms of disease.

The field of cancer detection has become like an arms race, he said: Who can find the most cancers?

"It's easy to find more cancers," Welch said. "The question is, who can find the cancers that matter?"

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