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Cancer By the Numbers

I mentioned cancer incidence versus cancer mortality the other day, and I wanted to highlight this NEJM paper, which is a recent and comprehensive look at the topic. You can see several different effects in the data. Hodgkin’s lymphoma, for example, has shown a pretty steady incidence rate over the past 40 years, but steadily declining mortality, which indicates a steady improvement in overall treatment. Pancreatic cancer (mentioned but not graphed in the article) has both lines holding steady: it occurs in the population at the same rate it always did, and over the 40-year span of the data we were sadly unable to do anything to improve the live spans of those diagnosed with it.

For chronic myeloid leukemia (CML), on the other hand, the incidence rate has also been steady, but there’s an abrupt improvement in the mortality figures that kicks in the during the late 1990s, shown at right. The scale is relative to the 1975 figures, and the decline is the introduction of Gleevec (imatinib). Anyone who worked on that one can look at that curve and know exactly what they accomplished. CML, as it turns out, is less genetically complex than most other types of cancer, and was thus well suited to be targeted by specific kinase inhibitors. Getting this to happen for more heterogeneous and mutation-prone tumors is a struggle indeed.

Interpretation of the data becomes trickier when the incidence rate itself shows a change, though. As the authors note, lung cancer is a good example: the incidence rate and the mortality rates moved in almost exact parallel from 1975-2015, which argues that both these effects are real and are tied together. These declines clearly seem tied to the overall decline in smoking: the cancer rates are just about thirty years behind that decline (lung cancer takes time) and they move right along with it. The post earlier this week about cancer news was prompted, in fact, by an apparent change in that tight correlation, because new therapies seem to be making lung cancer mortality decrease even more than the incidence rates would have predicted.

Stomach cancer is a case where the incidence rates and the mortality rates seem to have been steadily falling over the entire 40-year period studied (an effect seen across the industrialized world). There have been no great breakthroughs in overall diagnosis or treatment; it’s just happening less often. About half of that decline is attributed to decreasing H. pylori infection, and the rest to general lifestyle and quality-of-life changes. Cervical and colorectal cancer are in roughly the same category (incidence and mortality both going down), the latter starting its decline in the early 1980s.

And those last two bring up the issue of screening. Colorectal cancer incidence was actually declining before widespread screening was introduced, though – that one seems to be similar to stomach cancer and reflect a real decline in the underlying rate – and since both of these are associated with the digestive tract, they might both be broadly related to improvements in the food supply. Cervical cancer screening seems to have definitely had an effect on the data, and the fact that precancerous lesions are discovered and treated makes the decline on incidence rate especially strong. But screening in general does not make incidence rates go down – the opposite, in fact, which is what one might expect.

That shows up in the data for thyroid cancer, kidney cancer, and melanoma. Incidence rates for these have been climbing steadily (thyroid since the mid-1990s, melanoma across the whole 40 years), but overall mortality has stayed the same. And while treatment has improved, it has not improved nearly enough to cancel out such dramatic incidence increases – if those incidence increases were real. As the authors point out, these would seem to be clear examples of overdiagnosis. We are telling too many people that they have these cancers when they don’t – or at least, when they don’t have any form of them that they really have to do anything about. We are treating people who should not be treated and we are terrifying people who should not be terrified.

The messiest categories (you know these were coming) are breast and prostate cancer. Both showed large increases in incidence rate on the introduction of widespread mammography (1980-1990) and PSA screening (1987-early 1990s), respectively. But the prostate incidence rate has subsequently fallen, while the breast cancer incidence rate has remained at what may be a new, higher plateau. Meanwhile, mortality for both has declined, breast cancer since about 1990 (and more steeply in recent years, it seems) and prostate since about 1995. The resulting curves in both cases would appear to be a mixture of true incidence rates, overdiagnosis due to screening, and advances in therapy, and it’s not easy to untangle the relative effects of all these. Arguing about these matters has been intense, as many will have noted, but there seems little room to argue that both breast cancer and prostate cancer are indeed overdiagnosed.

Putting all of these together into overall cancer rate figures obscures as much as it reveals, to be honest. That’s because one thing I haven’t been mentioning is the relative differences between all these incidence rates. The overall cancer incidence rate for men looks pretty variable over the years, for example, largely because of those big changes in prostate incidence numbers (prostate having taken over as largest single category). For women, an earlier rise in incidence rate seems to have been driven by rises in lung cancer (mostly very real) and breast cancer (a significant amount of which may not have been). Thyroid cancer (over)diagnosis is hurting the incidence rate among women, who are three times as likely to get the diagnosis, although mortality rates are the same for both sexes. And for both men and women, overdiagnosis in melanoma and kidney cancer have made the overall cancer incidence rates look worse than they surely are.

Cancer mortality, though, has been declining across the board since 1990. And that’s hard to argue with, since death is a definitive endpoint for the data. There are an awful lot of people in the business trying to make sure that it goes down even further!


27 comments on “Cancer By the Numbers”

  1. anon says:

    American Cancer Society Report Indicates Cancer Rate in 2017 Hit Record Low

    The American Cancer Society issued a report this week that found that in the U.S., cancer death rates had declined in 2017 to its lowest levels for the 26th year in a row. President Donald Trump suggested in a tweet that his administration played a role in this, but the American Cancer Society pushed back on that a bit, noting he took office in January 2017.

    1. Anon says:

      He also took credit for the successful reaction I ran in my labs, but I ignored his brouhaha. It is always better to ignore the shenanigans. Our media gives him way too much coverage! If they all had collective wisdom to ignore him, all will be fine.

      1. cynical1 says:

        But he’s fighting windmill cancer! There’s a guy in my neighborhood running around with a MAGA hat destroying everyone’s whirligigs. And the Home Owner’s Association recently took up a vote on banning them altogether! New legislation will be introduced by Lyndsay Graham that proposes having the EPA ban them altogether due to their strong association with cancer along with an enhanced risk of autism that increases with the use of vaccines. If only Scott Pruitt was still here to save us all………..

    2. Vader says:


      Not everything has to be political.

  2. paperclip says:

    A number of molds secrete carcinogens, so I’m convinced that’s a food supply issue that led to increased stomach and colorectal cancer rates.

    1. Derek Lowe says:

      Not a weird hypothesis at all, I’d say.

    2. Mr. Rogers says:

      Of course, this leads to the question of what happens when you remove preservatives that prevent fungal growth.

      1. Neil says:

        Refrigeration and reduced use of nitrates/ites may have some impact on the incidence of stomach cancer.

        1. Barry says:

          “Until the late 1930s, stomach cancer was the leading cause of cancer death in the United States. So much for the “good old days.”

          The incidence of stomach has plummeted here since then. (But it’s still a big problem in developing countries.)

          Several reasons have been proposed for why it’s fallen here. One is that the increased
          use of refrigeration since the 1930s has made fresh fruits and vegetables with vitamin C more available and has decreased the use of salted and smoked foods.”

        2. John Thacker says:

          Although when one says reduced use of nitrates you mostly mean consuming less smoked food. It’s a weird fact that “no nitrates added uncured” bacon has as much or more nitrates than regular bacon, since it’s actually cured with celery salt and that produces nitrates, just oddly it doesn’t count for labeling because of being all natural or some nonsense.

          I recall that Japan, for example, has a high stomach cancer rate often attributed to their high consumption of pickled products.

  3. Peter Juhasz says:

    Co-morbidities could also complicate the accurate interpretation of these data. For instance, increasing prevalence of obesity and diabetes can plausibly have an interplay with gastrointestinal cancers – both through incident rates and mortality rates, but not necessarily in a correlating manner. Don’t claim to have insight but definitely seems plausible.

  4. matt says:

    Cervical cancer incidence rates should see a huge drop as a result of the HPV vaccine.

    for example,

  5. JIA says:

    @Derek — I’m puzzled by the way you have lumped thyroid cancer, kidney cancer, and melanoma together in the “overdiagnosed” category. To my knowledge, melanoma is invariably fatal if left untreated, and it’s close to 100% fatal if diagnosed and treated after metastasis. Yet if caught early, it’s almost 100% curable (by surgery). How then can it ever be “over diagnosed”? Don’t we want to diagnose every single case, as early as possible?

    If you had said that “skin cancer” was over-diagnosed, that might make sense; many types of lesions are indolent and non-fatal. But melanoma, specifically, is fatal. Can you please explain? Thanks.

    1. JIA says:

      Sorry — now having had time to read the linked NEJM paper, I see that this was the authors’ classification of melanoma as overdiagnosed, not yours. I remain puzzled. They define overdiagnosis as “reveal[ing] some cancers that would otherwise not become evident clinically”. Melanoma always becomes evident clinically, because when untreated, it kills people.

      Perhaps they have lumped benign lesions (e.g. pigmented nevi) with malignant melanoma. That is quite misleading, since benign nevi are by definition, NOT melanoma. In the 60s nevi could be called “benign melanoma” but that is no longer the case. According to the WHO 2018 classification: Melanocytic tumors are currently classified as nevi, considered benign; melanomas, considered malignant; and melanocytomas, considered borderline tumors.

      So I would want to check their source data. If they want to argue that benign nevi are overdiagnosed, they should separate the data from malignant melanoma.

      1. HFM says:

        Maybe they’re counting the early-stage stuff (the melanocytomas). Many of them wouldn’t have progressed all the way to metastatic disease. I can see how you’d call that over-diagnosed, but if I’m the patient, I’m not going to complain. Here’s a mole with a 5% chance of killing you…sure, I’ll deal with a minor outpatient surgery rather than take that risk.

        1. Steve says:

          absolutely true, but it still screws with any interpretation of cancer rates and treatments effciacy if your baseline diagnoses change as well over time

  6. loupgarous says:

    ASCO reports an increase in number of people diagnosed with neuroendocrine cancer by about 5%/year. This could be different from incidence, according to the ASCO website, because of improvements in imaging (e.g. Ga-68 dotatate PET added to the arsenal of diagnostics) –

    Some NETs take up MIBG, some take up somatostatin analogs such as dotatate, and within each of those categories, the radioisotope chosen as a label for positron-emission tomography (PET) seems to make a real difference . When I was first diagnosed with paraganglioma 20 years ago, indium-111 octreotate was just being used for PET diagnoses of NET. 18-fluorodeoxygluose (FDG) and gallium-68 have recently approved by FDA relatively based on improvenment in sensitivity for NET. I was in clinical trials for Ga-68 dotatate in 2014 and 18-FDG. Ga-68 dotatate is now how my tumor progression is tracked by my local oncology team. 18-FDG is used when fast-growing NETs are suspected, and recently got FDA approval as a diagnostic tool in Parkinson’s disease.

    That five percent/year increase in detection may stem from neuroendocrine cancers not being as rare as they were once thought to be – in other words, the increase in detection may not signal an increase in incidence of neuroendocrine tumors. Some of them may have been missed when PET generally was not used as often as now in the diagnosis of cancer, some missed when MIBG imaging was used for diagnosis of neuroendocrine tumors (as it was when I was being screened for recurrent disease, considered “cured” after negative MIBG findings, until I was found to have three large solid metastases from my original paraganglioma in my liver).

  7. loupgarous says:

    Speaking of 18-fluorodeoxyglucose, wikipedia’s article on [F-18]FDG looks interesting from a med-chem standpoint.

    Also, for sake of clarification – [F-18]fluorodopa, not F-18[FDG] was what recently got FDA approval for use in diagnosis of Parkinson’s disease.

  8. Barry says:

    Mortality from skin and colorectal cancers are down in great part because we find and excise them without waiting for them to check all the boxes. Pre-cancerous lesions are snipped and sent to pathology because the excision is so safe. Historically, cancer chemotherapeutics have been so toxic/mutagenic that no one would responsibly start treatment on a pre-cancerous lesion. That must change as safer agents come on-line. And that will require the FDA defining a “disease” that doesn’t check all the boxes.

  9. TheDonald says:

    Looking at all these numbers, it’s amazing how much Donald Trump has done to cure cancer, almost as if the disease was frightened that he would become president (I was), surely he deserves a Nobel Prize.

  10. Dylan Richards says:

    “over-diagnosed” could also just be diagnosed earlier, right?

    Also for breast cancer, I’m highly suspicious of estrogen-related compounds (endocrine-disrupting chemicals – EDCs) in drinking water/food/environment or even just the increased used of estrogen-based birth control, especially with the higher incidence of the use of birth control, the majority of which gets flushed down the toilet in urine. These effects have already been seen in fish populations being “gendered” toward extinction in the great lakes. That being said, these days you’re more likely to die from breast cancer treatment-induced heart failure (e.g., doxorubicin cardiotoxicity) than you are to die from breast cancer.

    1. Vader says:

      Meh. It’s possible you’re more likely to get infected from a polio vaccine than to catch wild polio if you’re living in the U.S. The vaccine is still a good idea.

  11. a. nonymaus says:

    Since I’m too lazy to read the linked articles, how much of a decrease can be explained by people missing their chance to get cancer by dying of other causes?
    The diseases of despair have been on the rise, as discussed in the following op-ed:

  12. Nile says:

    The ‘unmasking’ effect of longevity is probably a factor here: so, too, is the improved treatment of cardiovascular disease – an unknown number of people who survived a coronary will have the same lifestyle factors that lead to lung cancer.

    But that doesn’t detract, at all, from the achievements in cancer treatment.

  13. John Thacker says:

    The earlier lung cancer rise in women was I assume from getting over that period of time where women’s smoking increased, as it went from a masculine habit to one that women did also. The association of cigarettes with feminism and women’s lib goes back to the ’20s. The more socially conservative states were behind both in women starting to smoke and in quitting, producing regional patterns.

  14. AspiringVegetarian says:

    “Colorectal cancer incidence was actually declining before widespread screening was introduced, though – that one seems to be similar to stomach cancer and reflect a real decline in the underlying rate – and since both of these are associated with the digestive tract, they might both be broadly related to improvements in the food supply.”

    It is also worth noting that in 2015, the World Health Organization formally announced their classification of processed meat—”meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance flavour or improve preservation”—as a Group 1 carcinogen. In other words, we now have sufficient evidence to confidently state that eating processed meat causes colorectal cancer. This means that there is a similarly strong body of scientific evidence to support the carcinogenicity to humans of processed meats as there is for tobacco smoke and asbestos. For more info on this, see:

    Of even greater significance was their broader classification of red meat (i.e., “all mammalian muscle meat,” including “beef, veal, pork, lamb, mutton, horse, and goat”) as a Group 2A carcinogen. There is strong evidence supporting a link between red meat consumption and colorectal cancer, and more limited evidence of links to pancreatic and prostate cancer.

    While the formal announcement was only made in 2015, we have collectively known about the harmful effects of red meat for quite some time, and this increased awareness (and consequent improvements in our dietary choices) may be reflected in the data cited above, particularly for colorectal cancer.

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