One of the all-time classic comedy pairings was enshrined in cultural history in 1968, when Jack Lemmon and Walter Matthau appeared together in the original movie version of The Odd Couple. As well as spawning a hit TV show, the film christened a whole subgenre that sitcom creators still lean heavily on today. Charmingly, it also defined one of the entertainment industry’s more iconic offscreen friendships, which saw the two star in seven other films together, most of them in some way versions of The Odd Couple, including an actual sequel 30 years after the original. Here’s Walt and Jack promoting that movie in 1998, having finally morphed into Waldorf and Statler from the Muppets, talking about the moment they met — which, true to form, they can’t agree on.
When this lifelong grouchy bromance finally came to an end, it almost ran to Hollywood tragi-comic formula. Matthau died in July 2000 — from a heart attack, having developed colon cancer five years previously — and Jack Lemmon followed him exactly 11 months later, brought down by bladder and colon cancer. They now lie in the same cemetery in L.A. The fact that they shared a real-life disease as well as a fictional apartment and, ultimately, a patch of earth wasn’t fate, though, and it wasn’t Hollywood magic. In fact, it was barely even a coincidence. Instead, it’s an indication of just how prevalent colorectal cancer was, and remains, in the U.S.
For most of us the words “colon” and “cancer” describe two of the last things we’d want to think about on an average day. Add “rectal” to the mix and it’s a potent cocktail of okay-let’s-change-the-subject-shall-we. But for the moment, let’s not. Because there are a million reasons we should be thinking harder about it than we are — that’s around how many survivors of colorectal cancer are currently living in the U.S., the majority of whom are alive because they thought about it enough to submit to screening for the disease and their cancer was spotted early. Another reason to talk about it is that it is no longer a disease for the over 50 crowd: Due to factors that remain obscure and which we’ll get to in a bit, more and more people in their 40s, 30s and 20s are dying from it every year.
Yet it’s treatable. There’s a 90-percent survival rate for colorectal malignancies that have been discovered at a pre-cancerous or localized stage. Around three-fifths of cases are identified after the disease has progressed beyond this point, though, where the odds quickly start to look less favorable. As Stephanie Spanos, P.R. Manager for Exact Science (the company that, in collaboration with the Mayo Clinic, devised the Cologuard test — one of a number of innovative screening methods to have recently emerged as an alternative to the standard colonoscopy exam) puts it: “CRC is the most preventable, yet least prevented form of cancer.”
Since a few years prior to Lemmon and Matthau’s deaths, America’s colorectal cancer mortality rate has been falling at a steady pace among both men and women; among men, who are more susceptible to the disease, it’s declined by 53 percent between 1970 and 2016. Yet it remains the second most common cause of cancer death, after lung cancer, for men and women combined, and the American Cancer Society (ACS) estimates that 135,430 people in the U.S. will be diagnosed with either colon or rectal cancer in 2019 — and just over 50,000 of them will die from it within five years.
A big reason why is that many people who should be getting screened simply aren’t, partly because of the cloud of dread associated with the word “colonoscopy.” Granted, having a camera inserted rectally and having what looks like one of the sandworms from the movie Dune flexing and waggling around your most inner of sanctums isn’t everyone’s idea of tickle time (and to illustrate, here’s Kyle MacLachlan thinking about his colonoscopy, then committing to it by ritually summoning it out of the ground). Plus, the prep for the examination — typically a heavy-duty purgative followed by tract-cleansing waves of diarrhea — is notoriously unpleasant (just ask Ronald Reagan in 1985).
Plus, especially if polyps (pre-cancerous growths) are found and surgically removed during the procedure, a colonoscopy can be colossally costly. Added to all that, and possibly the strongest incentive to inaction, is the raw fear of the specialist actually finding something. You have plans for the next two weeks; you’re going on vacation in September — why jeopardize it all for the sake of a potentially life-saving diagnosis? (Here, by the way, is just about all the information you might want to consult on the detailed ins and outs of colonoscopy.)
So it’s easy to see why it keeps slithering to the bottom of people’s to-do lists. But the good news is that colonoscopies are no longer the only option for getting our gut walls green-lit. There’s now a buffet of first-pass options that don’t involve your being plugged with a cable like a human smartphone on charge, from blood tests to stool-sample kits you can do at home — a fact that many more of those put off by the traditional procedure need to be aware of. Which is partly why the Colorectal Cancer Alliance (CCA) has just begun funding a major project in Philadelphia to see if it can get screening rates among higher-risk groups up to 80 percent, while raising awareness among younger people that they should be concerned, too.
“The idea came about from a young man who lost his life in his 40s,” explains Michael Sapienza, CEO of the Washington, D.C.-based charity. “He said, ‘What if we took a pharmaceutical approach to screening?’ When Pfizer or any of the large pharmaceutical companies bring a new therapy to market they spend about a quarter billion to a half a billion dollars to just market that drug. And what if we spent that kind of money on screening?” So the CCA hired the consulting firm McKinsey to investigate feasibility, who predicted it would cost $350 million over the course of two years to get screening rates in the U.S. up to 80 percent. “That’s kind of amazing if you think about it,” says Sapienza: “How one drug company, just one, spends a quarter billion to a half a billion, but if we had $350 million, we could save a ton of lives. So we’re taking that same approach and doing it city by city, starting in Philadelphia.”
An important aspect of the drive in Philly is to wake people up to the fact that they can take action without having to undergo a colonoscopy, at least in the first instance. “We’ll be funding all different types of screening navigation,” says Sapienza, “whether that’s colonoscopy, whether that’s FIT [which stands for ‘fecal immunochemical test,’ a swab for blood in your stool that you can do at home], whether that’s Cologuard [another at-home test kit, which detects biomarkers for cancer in the DNA found in your poo, with a 92 percent success rate], whether that’s Epi proColon [a blood test carried out at a doctor’s office].”
“The number one thing that data has suggested over and over and over again is the reason why people don’t get screened,” he continues. “Yes, because of fear and the rest — but the biggest is that they just don’t go. They’ll make the appointment for their colonoscopy, or they’ll get a prescription for a Cologuard or an FIT test, but they actually don’t take the extra step to do it.”
All these non-invasive test options have their strengths and weaknesses in terms of sensitivity, targeted detection and patient-friendliness. The FIT test, for example, is supposed to be carried out by those in higher-risk groups annually to be effective, and requires an ability, which doesn’t come easy to everyone, to scoop poop onto a swab card. Stephanie Spanos from Cologuard points out, “Fecal blood tests, such as FIT, only detect blood in stool, which is one marker [of cancer being potentially present] and are unable to detect polyps or lesions if they’re not bleeding.” Meanwhile, her own company’s “breakthrough sDNA [‘s’ for ‘stool’] technology analyzes and detects 11 distinct biomarkers that could be associated with the presence of cancer or precancer.” The test works because “DNA is shed naturally and routinely from cells in the intestinal lining, where it’s passed into the stool.” According to ACS recommendations, Cologuard tests need only be carried out once every three years.
But Spanos isn’t necessarily being partisan in her analysis. She says, “It’s important to point out that there are multiple screening tests available and evidence has shown that offering patients options can help get more people screened. Patients should talk to their health-care provider to determine the option that’s best for them.”
Her ecumenical advice is echoed by Sapienza. “We don’t recommend any test over another,” he says. “What we say is the best test is the test that gets done. But the data supports the colonoscopy as still the gold standard.” The old fashioned camera tour of the colon has been shown to be effective in finding polyps and cancers 95 percent of the time, and has the added benefit that many of these growths can be safely removed there and then, as part of the procedure. The perennial problem, Sapienza points out, is that “it’s only about 45 percent of the at-risk public getting a colonoscopy.”
“You have to look at these things together,” he argues. “Both the sensitivity of the test and how many people are actually going to do it. Because there’s a lot of people that don’t want to have a colonoscopy, so we have to be very responsible about talking about these other options, whether it’s Cologuard, FIT, Epi proColon — those tests are still effective, if you do it in the prescribed timetable, making sure you go back when you’re required.”
Indeed, at-home screening is increasingly popular. Since Cologuard was approved by the FDA in 2014, for example, more than 150,000 healthcare providers have administered it to over 2 million Americans. Despite this, the medical profession won’t be retiring their colonoscopes any time soon. “I don’t think the colonoscopy will ever be phased out,” says Sapienza, “because it’s a test that cuts out the cancer, or cuts out pre-cancer. All these non-invasive tests could potentially save money, they could allow more people to get screened, but you still have to have a colonoscopy to remove those polyps.” Essentially, if your Cologuard, FIT or any other test comes back positive, the next step is still a tube ride — all the way south, on the brown line.
Scope for Improvement
If you’re under the age of 50, you shouldn’t assume this can all wait till you’re picking out roll-neck sweaters and responding positively to the smell of pipe tobacco. Alarmingly, while colorectal cancer diagnosis rates among the over-50s have been dropping by around 3 percent each year since 2004, according to a statistical survey published by the ACS in 2017, since 2000 there have been 1.6 percent more cases of colorectal cancer per year showing up among adults under that age. “The increase was driven solely by tumors in the distal [i.e., the lower part of the] colon and rectum,” say the paper’s authors, who add that this rise “has also been reported in other high-income countries, including Norway, Australia and Canada.” While unable to account for it, they suggest “factors thought to have contributed include increased prevalence of excess body weight, as well as changes in lifestyle patterns that precipitated the obesity epidemic, including unhealthy dietary patterns and a sedentary lifestyle.”
“This increase in young-onset colorectal cancer is happening around the world,” confirms Sapienza. In response, the CCA has spent $1 million in the past year into looking at what might be driving it. Although the search for an answer is just beginning, “there are some thoughts,” he says. “Is it our microbiome? Is it what we’re eating? Is it lifestyle and environment? Is it that we’re washing our hands or using antibacterial soap too much, so we’re not developing the immunity to things in our gut? Those are the main pieces. Right now, we’re still looking at whether there’s a biological difference — meaning, is the tumor’s makeup when you’re under 50 different than the tumor makeup of folks over 50? We still don’t have evidence to support any of these hypotheses yet, but that’s what we’re funding research to find out.”
What will more clearly put you in a higher-risk group for young-onset CRC is a family history of the disease. While only 4 to 6 percent of diagnoses are thought to be truly hereditary — meaning susceptibility to the disease has been genetically inherited from a parent — between 30 and 40 percent of cases are classified as “familial,” where another family member’s colorectal cancer could indicate a shared predisposition to developing it. Sapienza’s mom died from colorectal cancer on Mother’s Day 10 years ago. “I would be familial,” he says. “My mom had it, and now I know. But prior to her getting the disease, there had been no family history, which means cancer was classified as ‘sporadic’ — that is, impossible to predict.”
Aside from the blood tests, the stool-DNA tests, and variations on traditional endoscopic methods such as “virtual colonoscopies” (which use X-rays to map the gut), there are even higher-tech solutions currently in development. These include: Capsule endoscopy — miniature cameras encased in a pill that you swallow, which are already in very limited use for colon screening; capsule robots on a similar scale, which have been prototyped to be controlled via magnets external to the patient’s body and even to perform surgical procedures such as polyp removal. And in the future, artificial intelligence combined with detailed public-health data could identify individuals at higher risk much sooner — at least one health-data analytics company, Medial EarlySign, based just outside Tel Aviv, is focusing its efforts on colorectal cancer as a susceptible target for a data-based approach. “Data potentially could connect the dots for family-history or hereditary colorectal cancer, and that’s still 30 to 40 percent,” says Sapienza. “So could we get 100 percent of that 30 percent screened? That could be very helpful.”
But he points out, Big Data and machine learning wouldn’t have helped his mom. “Unfortunately, 50 to 60 percent of colorectal cancers are sporadic. Meaning you didn’t have a family history, you ate right, you didn’t do anything wrong, you didn’t drink too much or eat too much red meat.” Nevertheless, he thinks that “any innovation in screening is really exciting; any way to get additional people screened is going to save lives.”
While eradication may be some way over the horizon, the fact that survival rates track upwards with screening rates makes Sapienza optimistic. His overriding question is: “Can we make it a chronic illness instead of a death sentence? We’re really working hard to try to get new, young investigators into this field, so we can see more of those novel approaches, and hopefully in a couple years those types of investigators will be the ones who are bringing new innovative techniques to the market.”
Meanwhile, the growing array of non-invasive alternatives to colonoscopy should mean that clinicians and patients alike shouldn’t have to think twice about triggering a screening at the slightest hint that one might be needed. “We’re currently exploring updates to further differentiate Cologuard as a front-line screening test by increasing specificity and sending fewer people to unnecessary colonoscopies,” says Spanos. “Working with the Mayo Clinic, we’ve discovered promising biomarkers for an evolution of the current test and are excited about the potential to make Cologuard an even better test.”
Francis Crick, the Nobel Prize-winning British molecular biologist who was a joint discoverer of DNA’s double-helix structure back in the 1950s, would no doubt be proud that the molecule that made him famous, when harvested from human feces, is being used so effectively to save lives. Especially since Crick himself died from colon cancer, aged 88, in 2004. Again, though, just like the Odd Couple, this fact doesn’t count as irony, Murphy’s law or a quirk of fate: It’s simply cold, hard statistical likelihood — the mapping of mathematical probability onto lived reality that underlies all biological progress. As the U.S. Preventive Services Task Force sets out in their screening guidelines, “the greater number of eligible patients that receive screening, the greater reduction in CRC deaths.”
So if you think you might be at risk, and you want to be on the right side of the graph, don’t just consider getting yourself screened. If it’s a “gold standard” test, perhaps rebrand it in your head as a MacLachlanoscopy, and ride the sandworm. Or if you really can’t face it, talk to your doctor about some of the other options that are out there. But just get it done, by fair means or foul.