Why Cancer Death Rates Have Decreased Over The Last 30 Years

JOHN DANKOSKY: This is Science Friday. I’m John Dankosky, sitting in for Ira Flatow.

Now, there’s a word that you never want to hear in the doctor’s office. It’s “cancer.” About 40% of us, though, will be diagnosed with cancer at some point during our lives, the most common being breast, prostate, and lung cancer. That’s according to the National Institutes of Health.

But just in the last couple of decades, major progress has been made in the world of cancer treatment and prevention. And the breakthroughs made from the development of the mRNA COVID vaccines are bringing even more promise for hard-to-treat cancers. Cancer death rates have steadily gone down over the years, and the Biden administration’s Cancer Moonshot program aims to reduce that number by at least 50% by 2050.

Here to give us a broad update on what progress cancer researchers have made recently is my guest. Dr. Siddhartha Mukherjee is assistant professor of medicine at Columbia University. He’s also the author of the Pulitzer Prize-winning book, The Emperor of all Maladies, The Biography of Cancer.

Dr. Mukherjee, welcome back to Science Friday. So good to have you.

SIDDHARTHA MUKHERJEE: My pleasure. Thank you for having me.

JOHN DANKOSKY: So I’m sure that you get this question a lot, but to kick off our conversation, why exactly are cancers so hard to treat compared to other diseases?

SIDDHARTHA MUKHERJEE: Well, cancers are, as you just pointed out, is a word in the plural. There’s not one cancer, but many cancers. In fact, even if you look within one subtype of breast cancer, you’ll find many, many sub-subtypes of breast cancer. And each one demands a different kind of treatment because they are genetically different. Cancer is not one disease, but many diseases. And in each case, we’re trying to figure out what the commonalities or the differences are. And that’s made it a very different problem than, for instance, another disease like diabetes, where, for the most part, it’s a problem with insulin and insulin signaling.

And that’s where you have the central conundrum, which is that it’s not one disease, but many diseases. And each disease has its own solution and its own problem.

JOHN DANKOSKY: When exactly did we start to realize just how complicated a problem this is, that you have all of these different types of diseases that behave in different ways?

SIDDHARTHA MUKHERJEE: Well, there was an inkling quite early on when physiologists, in the 1940s and ’50s, began to realize that the same therapy applied to the same cancer could lead to very, very different results. Take childhood acute leukemia– by the 1960s, 60% to 70% of children were being cured using intensive chemotherapy, but 30% to 40% were not being cured. So there was a question already, what was different about those children? Their cells look the same, as far as we can tell, under the microscope, but there’s something different. And then, since the 1970s, ’80s, and ’90s, when cancer genetics became more and more predominant and understood, it became quite obvious that the genetics of cancers, even within a particular subtype– let’s say leukemia– are very different from each other.

And so I think it was a gradual dawning of the idea that there’s not one, but there are many kinds of cancer, even within a particular subtype.

JOHN DANKOSKY: I think many of us grew up with the idea that we had a few major types of cancer treatments. There’s surgery, there’s radiation, and there’s chemotherapy. Talk, if you would, about some of the new approaches that have come on the scene in just the last couple of decades.

SIDDHARTHA MUKHERJEE: So let’s begin with the most important ones, which is cancer prevention. You have to think about cancer as a disease that can be prevented, detected, and treated. And it’s a pyramid. The bottom of the pyramid is prevention. The middle of the pyramid is detection. The top of pyramid is treatment.

In cancer prevention, we’ve had a small revolution of sorts in understanding the role of inflammation, and a very particular kind of inflammation. People often say, what does inflammation mean? Inflammation means many different things to different people, but a particular kind of inflammation seems to be able to incite cancer cells to grow. And so a lot of effort is being put into figuring out what that inflammation is, how to prevent it, what causes it.

For instance, we now know that air pollution, of all things, is a strong inflammatory signal for the growth of particular kinds of cancer. We now know that, most likely, agents that we knew as potently cancer causing– carcinogenic– such as asbestos, may have a very inflammatory component. So identifying that inflammation has become a very important part of cancer prevention.

The second piece is early detection. These trials are still in progress. I’m optimistic about them, but they’re still in progress. Can we detect cancer in its earliest phases? Some of them have been phenomenally successful– colonoscopy, a great example; mammography, less obvious an example, but also has had impact; pap smearing; and of course, again, in the prevention realm, cancer vaccines, such as vaccines against human papillomavirus, which causes cervical cancer. Finally, treatment gets a lot of attention. In treatment, we have the first use of rational, or targeted, immunotherapy– the use of the body’s own immune system to go and kill cancer cells within the body.

And to that, if you add new forms of therapy, such as targeted therapy, against the disabled particular genetic mutations that goad the cancer cells to divide, we have a whole new range of cancer treatments.

So again, to summarize, a lot more going on in prevention, with the identification of new states, such as inflammatory states, that guide or goad cancer cells to divide and grow, and an understanding of how to prevent that; in early detection; new vaccines; and the possibility of detecting cancer early to cut it out early– still in the middle of trials, still undergoing evaluation; and in cancer treatment, new targeted therapies, and most importantly, immunological therapy against cancer.

JOHN DANKOSKY: I guess I’m wondering if these three pillars here– the prevention, the detection, the treatment that you’ve talked about– if you view these as all equally important toward these declining numbers that we’re seeing, because we have seen cancer death rates go down in general. Is there one of these three that has been more important, in your mind, than the others?

SIDDHARTHA MUKHERJEE: Almost certainly prevention has been important. Virtually every disease that we know about in medicine has been most impacted by prevention. Cardiovascular disease, a great example. Changes in diet, lifestyle, changes in blood pressure management, changes in management of cholesterol, et cetera, are all preventative measures. They prevent heart attacks before they happen. And that’s been the driver of the decline in cardiac death.

And so, by the same logic, almost certainly prevention has been the major driver in the decline in cancer-related deaths from various kinds of cancer, including, most importantly, lung cancer– prevention of smoking; other cancers– cervical cancer, the vaccine against human papillomavirus; and changes in diet, lifestyle, and others caused a decrease in cancer deaths by preventing cancer from coming up overall.

JOHN DANKOSKY: How big has this drop been?

SIDDHARTHA MUKHERJEE: Hard to summarize. Lung cancer and cancers related to smoking, a massive decrease over the years. Other cancers– pancreatic cancer– much less so. But overall, I would say that the numbers released annually by the various institutions, including the National Institutes of Health, have shown about a 1% to 2% decrease in mortality every year. Which sounds small, but over 25-odd years, that’s a 25% to 30% decrease in mortality from cancer over the last 25 to 30 years. That’s a big number. That’s a big leap.

JOHN DANKOSKY: Speaking of big leaps, as I mentioned in the introduction, the Biden administration has a goal of reducing the death rate by at least 50% over the next 25 years. Is that an achievable goal in your mind?

SIDDHARTHA MUKHERJEE: If we keep on that 2% trajectory, which we can by doing more research, by funding, more research, by understanding of prevention in particular, but also treatment, I think that a 2% decrease per year is a reasonable goal. And a 2% decrease every year will actually cause a 50% decrease over 25-odd years. So I don’t think it’s unreasonable. It just means that the momentum has to be kept up. It’s not an unreasonable goal.

People say, oh, it’s a pipe dream. It’s not. We’ve been seeing a 1% to 2% decrease every year across cancers. Some we need more attention than others. I gave you some examples. Glioblastoma, brain cancer, pancreatic cancers, and others need more attention. But overall, I think that a 1% to 2% decrease every year is a reasonable goal, and has been achieved over the last few years.

JOHN DANKOSKY: Because there’s such a disparity in the types of cancers and how we’re able to treat them and prevent them, I guess I’m wondering if you can give us an example of a type of cancer that didn’t have a lot of treatment options available, but nowadays, if you were diagnosed, it really wouldn’t be as big a deal. It would be something that you could probably tackle in some way.

SIDDHARTHA MUKHERJEE: There are several examples. I’ll give you a couple. The most striking one is a kind of leukemia, called chronic myelogenous leukemia, CML. It used to really be a death sentence 30-odd years ago– very bad treatment and transplant. It is highly manageable. Most patients now take a single pill, and they’re basically on that pill for life. And as far as everything is concerned, their cancer is in a protracted remission.

In the middle ground would be a cancer like multiple myeloma. Multiple myeloma is a cancer of blood cells. It lives in the bone marrow. Rapid advances over many years have caused that cancer, year after year, to have a greater and greater response rate to these medicines, so much so that we can now see that, over the last 10-odd years, there’s been an incredible improvement in the treatment of myeloma. It’s still an incurable cancer, but it’s a chronic disease. And many patients have lived 10 years, 15 years, 20 years with multiple myeloma.

On the far end of the spectrum, of course, you have metastatic pancreatic cancer, metastatic gallbladder cancer, and other forms of cancer, where we haven’t seen much improvement in the last decade or so. And those remain real mysteries and frontiers in cancer therapy.

JOHN DANKOSKY: You’ve mentioned this in the mysteries involved. What can you tell us– and let’s just take pancreatic cancer, for instance– what can you tell us about why there’s such a mystery? What is it that’s so particularly difficult or troubling in terms of how we treat pancreatic cancer?

SIDDHARTHA MUKHERJEE: Well, there are several reasons, and there are several unknown reasons. There’s known unknowns and unknown unknowns. So let’s talk about the known unknowns. The known unknowns are pancreatic cancer has a set of mutations– genetic changes– that drive the cancer that don’t seem to have very good drugs against them. So we can’t generally apply good drugs against pancreatic cancer.

In the unknown unknown category, for some reason, these pancreatic tumors are not very responsive to the immune system. So there’s a huge spectrum even within pancreatic cancer. Why they don’t respond to immunotherapy, we don’t know. It’s unlike, for instance, melanoma, which responds very well to immunotherapy. It’s unlike, for instance, childhood leukemias, which respond very well to chemotherapy. It’s a unique unique. And in some cases we know the answer and in some cases we don’t.

JOHN DANKOSKY: We’ve been talking a lot about death rates from cancer, but it’s a bit of a different story for cancer incidence rates, which are actually going up. What can you tell us about that?

SIDDHARTHA MUKHERJEE: It’s very difficult. Your audience needs to understand that cancer incidence rates are very important to distinguish from death rates. Cancer incidence rates can rise in real terms and can rise in false terms. In real terms, by that I mean really something is going up because of some reason that we don’t understand or we do understand.

In false ways, cancer incidence can seem to rise because we’re detecting cancer better. So just to give you an example, if we were to deploy a test that was to detect cancer early– a great example is in South Korea– many years ago, they started giving ultrasound machines to doctors’ offices. And the incidence– the incidence– of thyroid cancer went up dramatically, but the death rate from thyroid cancer didn’t go up at all. So that means that we were detecting much, much more, because you can put a machine next to someone’s neck and say, oh, you have thyroid cancer. But those cancers are never likely to kill you. Those cancers are not a problem.

So incidence is something we need to be very careful about, that truly, in some cases, incidences of cancers that are rising. And that’s real. But in other cases, there are incidences that are rising that are spurious. So I always say– when people say, oh, the incidence of X cancer is increasing, I always say, well, was there a new test? Was there a new way of detecting these cancers that suddenly became available? And don’t be fooled by that because that is just a false– that is just a spurious result.

That said, there are some incidences that are truly rising– colorectal cancer– colon cancer and rectal cancer in young men and women. We don’t know why it is rising. Esophageal cancer– cancers of the esophagus– in young men and women was rising because of alcohol and cigarette smoking. So there are some true spurious ones and there are some true real ones. We need to distinguish between them. But don’t get fooled by the idea that just because an incidence rises means that there’s more cancer around. It may mean that we’re detecting more of it, but it’s actually just been the same.

JOHN DANKOSKY: Before we run out of time, I want to talk a bit more about cancer vaccines, which we’ve talked about on the show before. Can you tell us a bit about what promise you see in this particular therapy?

SIDDHARTHA MUKHERJEE: Cancer vaccines are early in their development. Cancer vaccines are an idea that you could create a personalized immunological way by which the immune system could be incited to attack your particular cancer. And in an early study in pancreatic cancer, with a lot of work, a number of companies have shown that you can create a personalized cancer vaccine.

These studies are very early. I would warn people against over-interpreting them. They have not been subjected to what would be called the gold standard, a phase III study. There’s a lot of promise, but there’s a lot to be done before we can make a conclusion about whether these cancer vaccines are real, whether they have real benefit, and whether they can be really scaled to patients across the board in various forms of cancer.

JOHN DANKOSKY: What is something that is on the near-term horizon, you think, in cancer treatment that you think will help us get to that big leap? I mean, what are you really excited about right now, Siddhartha?

SIDDHARTHA MUKHERJEE: I’m excited about ideas that are completely new in cancer therapy. So can we exploit the metabolism of cancer cells? Cancer cells digest and metabolize nutrients differently from normal cells. Is that a way that we can exploit them such that we can choke off the cancer cells’ metabolism? I don’t know. That would be interesting.

AI is very interesting because AI can produce new medicines against cancer that didn’t exist before, couldn’t exist before. And so we’re looking at a number of AI efforts to understand what’s wrong with the cancer cell, and can we make new medicines against it.

And finally, of course, the enrollment of clinical trials, particularly in prevention trials, to try to see how we can prevent cancer and enroll patients in trials for the early prevention and early detection of cancer.

JOHN DANKOSKY: Do you feel, overall, positive about where we are right now in terms of cancer research? I mean, when people get a diagnosis of cancer right now, it’s a much different thing than if they’d gotten a diagnosis 20 or 30 years ago. Are you feeling particularly positive about where we are right now in terms of our research efforts and what you think is coming up next?

SIDDHARTHA MUKHERJEE: Look, this is a killer disease. It depends on the kind of cancer. There’s a lot of work being done on various kinds of cancer, lots of frontiers being pushed, everything moving simultaneously. Do I feel optimistic? Yes, I feel optimistic, as long as we can sustain the effort– this 1% to 2% decrease. If we stop the effort, I feel pessimistic. So my optimism is dependent on whoever the new administration is, rededicating its life and effort in that direction, and increasing the funding for research and development of new cancer therapies. If that’s the case, I feel optimistic. And we’ll see if that’s the case or not.

JOHN DANKOSKY: Dr. Siddhartha Mukherjee is assistant professor of medicine at Columbia University. Thank you, as always, for speaking with us and lending your expertise. I really appreciate it.

SIDDHARTHA MUKHERJEE: My pleasure. Thank you very much.