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Cancer medicine generates enormous revenues but marginal benefits for patients? (scientificamerican.com)
186 points by jwblackwell on Feb 15, 2020 | hide | past | favorite | 123 comments



This article is a case study in “if you say something controversial enough, people will pay attention regardless of the quality of your argument.”

There’s a lot of hype in the cancer industry and there are still many diseases that can’t be treated effectively. But the bizarre claim that we aren’t any better at treating it than we were 50 years ago is just wrong.

The timing is particularly ironic, coming after a decade of particularly rapid progress. The survival advantage conferred by immunotherapy is very meaningful, and it’s being used in diseases that were previously intractable. The author waves away the benefits of immunotherapy while focusing on the cost and side effects. Undoubtedly, it is expensive, and speaking from experience, the side effects aren’t fun. But the cost will come down, and the side effects are generally more manageable than chemotherapy.

If I really steelman the article, I can see a couple decent points and maybe even agree with them. I might believe that aggressive screening is counterproductive, for instance. But for an article complaining about “hype”, this piece is a remarkable sequence of exaggerations, fallacies, cherry-picked data, and hand-waving.


It is argued in the article that the survival rate didn't go up, but rather how it was measured: earlier detection means a longer period of survival since detection.

You argue that there was rapid progress in the last decade. The article agues the opposite (over decades even). It does this with citations and meta analysis where they find that much of the 'rapid progress' is not replicable. The article doesn't say that immunotherapy is not meaningful, but it does say it is over sold where there is hardly evidence of their benefit.

You also argue that the cost will come down, however there is no evidence for this. To the contrary even: according to the article it is going up significantly without any indication of improving.

Why do you state that the "bizarre claim" of not having improved treatment is "just wrong" without providing any supporting evidence for this?


Re: cost - you're conflating two different things. The cost of new drugs at the time of introduction has gone up. The new drugs of 2020 are more expensive than the new drugs of 2000. However, with a few high-profile exceptions, the cost of any individual drug goes down over time once generics are introduced.

The expensive new drugs of today are the affordable generics of tomorrow. Biologics are genuinely expensive to manufacture, so the cost of the current generation of immunotherapies will remain substantial, but it will ultimately drop to a fraction of what it is today.

Re: survival benefits - population level data about overall survival is tricky to get right, and issues like earlier detection leading to longer measured survival without actual benefit are real. And I'm sure that if you tweak the statistics just right, you can argue that all of the advances of the last 50 years have accomplished nothing. But that ignores a hugely important fact: we have randomized controlled trials showing that people who get these drugs live longer than an identical population that doesn't get them. I was going to spend a while finding citations, but let's go with the comment /u/dannykwells just posted:

"This article is absolute 100% bullshit.

-Metastatic melanoma: used to be lethal, now 50% cure rate.[1]

-Non small cell lung cancer: same, now around 25% [2]

-Breast cancer used to have a terrible prognisis, now 75% survive. [3]

-Not to mention the myriad of blood cancers with new, strong, cell therapy treatment options with 40-50% durable cure rate.

I don't know this person, but seriously, whoever he is, fuck you dude. Millions of us work day and night trying to improve care, and 99% of us arent getting rich.

[1] https://www.nejm.org/doi/full/10.1056/NEJMoa1709684

[2] https://www.nejm.org/doi/full/10.1056/NEJMoa1801946

[3] https://www.breastcancer.org/research-news/20100930"


All these arguments are just arm chair discussions by people who have literally zero knowledge or involvement in cancer treatments. The overall 5 year survival rate has increased significantly and for some types it has increased multiple-fold thanks to new drugs. And regardless, even in types with lower success rates the side effects are generally way more manageable than traditional chemotherapy.


If we diagnose earlier, it's expected that the 5Y survival rate improves even if the patient dies at the same age as she would have in the counterfactual.


Sure, that can show up in aggregated statistics. But it used to be that there was no treatment for all sorts of metastatic diseases. Now there are. That's not a function of earlier detection. This isn't made up; we have real RCTs demonstrating this stuff....


The people who don't know what they are talking about (or are maliciously feigning ignorance) are those who look at 5 yr survival without considering the effect of increased surveillance/screening. https://en.m.wikipedia.org/wiki/Lead_time_bias


You have to distinguish between screening detected cancer and symptomatic cancer. 5yr srvl rates say little in the former case but they are relevant for the latter. You'd really prefer having skin cancer today than ten years ago.

Your short exchange of arguments is a good example of what goes wrong in the public discussion.


I don't understand what you mean by "detected cancer" and "symptomatic cancer". Eg if a cancer is already detected then by definition it is impossible to screen for it.


(Screening detected) Found during a routine/annual colonoscopy/mammogram/etc...

vs

(Symptomatic detected) Hey, what is this lump here? Why am I so tired? etc...


I see, it should have been written "screening-detected" to be as clear as possible.

Yes, the latter is more likely to be comparable over time but it will still have issues with changes in how likely someone is to report it to their doctor, etc.


Look, just because a bias exists doesn't mean that it explains every single bit of improvement. We have randomized controlled trials showing that these drugs work.


Immunotherapies have a significant increase in survival rates of metastatic cancers i.e. cancers that were for the most part not detected early.


Except for one throwaway sentence about life extension averaged across 72 drugs, the huge point the author is missing is that the mortality rate is not what matters. The drugs aren't curing cancer - they're extending the lives of those with cancer, even though those same people eventually die of cancer. That won't show up in the mortality rates that aren't improving, but it's a very important positive effect of the drugs, particularly if that extended period of life can be at an acceptable quality. The industry actually measures its success by "quality adjusted life years," not by mortality, and I think that's the correct measure.


Would you not agree that spending hundreds of thousands for a few additional months of fairly low standard of living (even if higher than before) is wasteful on the larger scale?


That depends. As long as new drugs provide incremental impact, the benefit should be cumulative over time. Maybe not the area of healthcare spend with the highest ROI, but not a waste in isolation


> The drugs aren't curing cancer - they're extending the lives of those with cancer,

They often aren't doing that though, and if they are they're only doing it on average for a couple of weeks and are causing significant side effects. That "on average" means that for some people they're shortening life.

> particularly if that extended period of life can be at an acceptable quality

It usually isn't.

https://www.bmj.com/content/357/bmj.j2097


They say it’s two months on average.


This is one of those cases of huge variation between each case which makes the average useless. Metastatic melanoma can go upwards of 5 years while others might still be futile.


The author doesn't wave away the benefits. He says they are real but only apply to specific cancers which account for a small fraction of those diagnosed. Are his statistics wrong? It seems you benefited, but this isn't a counterargument.


So I'm looking back over what he wrote:

> Immune therapies, which seek to stimulate immune responses to cancer, have generated enormous excitement. Two researchers won the 2018 Nobel Prize for work related to immune therapies, and a new book, The Breakthrough: Immunotherapy and the Race to Cure Cancer, claims that they represent a “revolutionary discovery in our understanding of cancer and how to beat it.”

> According to a 2018 report in Stat News, drugs firms aggressively market immune therapies, and patients are “pushing hard to try them, even when there is little to no evidence the drugs will work for their particular cancer.” A 2017 analysis by oncologists Nathan Gay and Vinay Prasad estimated that fewer than 10 percent of cancer patients can benefit from immune therapies, and that is a “best-case scenario.”

Perhaps he's implicitly acknowledging that there are benefits, but in an article that essentially claims that cancer treatment doesn't accomplish anything, I interpreted it as being dismissive of the benefits. Maybe your reading of it is more reasonable.

The analysis underlying the 10% figure is basically correct. In fact, I think that article [0] is a narrower form of what this article would be if it were better: a harsh acknowledgment that immunotherapy, as the most meaningful breakthrough in the last couple decades, is being overhyped. The benefits are real, but writing books about it with subtitles like "The race to cure cancer" is deeply irresponsible.

Again, though, it's a matter of interpretation. They derived that 10% figure basically by multiplying: ~31% of cancers have approved use for immunotherapy, and it averages a 26% response rate. That 31% is a bunch of solid tumor cancers that didn't really have any particularly effective options beforehand. So for the 1/3 of least tractable cancers (~600k cases per year in the US), we now have something that benefits a quarter of patients. Is that enough? No. But it's still pretty amazing.

[0] https://www.statnews.com/2017/03/08/immunotherapy-cancer-bre...


My understanding is that immunotherapy has been shown to work great for cancers without solid tumors and results have been disappointing with solid tumors. It isn't that it's marching steadily forward and will eventually have been shown successfully everywhere.

I think people running down John Horgan's editorial keep citing successes -- multiple myeloma! cured! -- but aren't addressing his overarching argument, which, as I understand it, is that people are being sold false hope in the majority of cases -- familiar cancers like breast cancer, lung cancer, prostate cancer, colo-rectal cancer -- which has the negative consequences of impoverishing them and increasing their suffering for negligible benefit.

To be clear, I don't have any horse in this race aside from insurance bills.


Most of the indications for immunotherapy are cancers with solid tumors. This source [0] is a bit dated (2017) but it contains a chart showing which cancers had an indication for immunotherapy at the time, and they're almost all solid tumors. The initial approvals for the big immunotherapy drugs were for melanoma and non-small cell lung cancer.

[0] https://www.statnews.com/2017/03/08/immunotherapy-cancer-bre...


2017 is a bit dated?


The first immunotherapy was approved in March 2011. An article from 2017 listing diseases with approved immunotherapies misses fully 1/3 of the years (3 out of 9) in which immunotherapies have been approved.


Makes some sense, but that got me wondering if medical guidelines are going to start getting updates every few weeks like web browsers do.


This seems, then, like another good example why it doesn't make sense to talk about cancer as a single epidemic, but a set of similar diseases, some of which we've made better progress on than others.


100% agree. In fact, even specific cancers are really a collection of disease. For instance, breast cancer is many different diseases defined by different mutations/receptors and with correspondingly different treatment approaches.


I'm not sure how that's even relevant since any life saved counts( and this isn't a valid argument against releasing a new drug). Anyway yes, depending on the country of course but e.g. metastatic melanoma which was a death sentence has much better survival rates nowadays. You can also look up the small cell carcinoma 5 year survival rate with nivolumab for example. A similar thing is happening with more specialized drugs applied in specific stages of other cancer types in which case yes, the point that it's a small fraction of cancers holds true, but again, how is that an argument?


>The timing is particularly ironic, coming after a decade of particularly rapid progress. The survival advantage conferred by immunotherapy is very meaningful

Can you post some resources that support this with numbers?

>this piece is a remarkable sequence of exaggerations, fallacies, cherry-picked data, and hand-waving.

Could you point me to the fallacies and exaggerations in the article?


There are a lot of statistical fallacies like this:

> The current age-adjusted mortality rate for all cancers in the U.S., 152.4 deaths per 100,000 people, is just under what it was in 1930, according to a recent analysis.

The US is a very different population than it was in 1930 in ways that go beyond age. If you want to make a statement like this to point out that changes to lifestyle (e.g smoking/obesity) can totally offset medical progress, then go ahead and make that argument explicitly. But simply citing the headline mortality number to argue "LITTLE NET PROGRESS AFTER 90 YEARS" is unjustifiable.

Edit: As far as evidence of efficacy, here's a more-or-less random clinical trial showing a meaningful survival benefit for melanoma patients given ipilimumab (the first cancer immuotherapy):

https://clinicaltrials.gov/ct2/show/results/NCT00636168?view...

Note that ipilimumab is no longer the standard of care for melanoma as pembro has even higher efficacy.

There are a lot more trials out there if you're inclined to spend time looking through results.


A lot of times with cancer the best course of action is to do nothing. We try to treat a lot more late stage cancers now that have very low success rates than we used to.

The side effects are easy to dismiss when you survive. When you watch someone go through it and they don’t survive, it’s worse than had you done nothing at all.


I get a 20 minute drip of Pembrolizumab every three weeks. I had it done two days ago. 28K per infusion.

The cancer has spread since I have been taking it. But I don't know if the cancer is spreading slower with taking it or not.

I'm 1.5 million deep in medical bills from the last year. I no longer open my mail or answer my phone. I am just waiting for the day I go in for treatment and they turn me away.


I'm so sorry for you, US healthcare research is amazing and US healthcare availability is really bad at the same time.

My girlfriend in Hungary got all her cancer treatment for free, even if it's a quite poor country compared to the US.


You're confusing things.

Healthcare sometimes has a perverse supply curve, meaning the more expensive it is, the lower the quality. This is true of many drugs: there are generics whose side effects are well understood and have stood the test of time. They're so good that they are still being demanded and prescribed despite newer alternatives with incredible marketing and doctor incentives, glamorous salespersons, all-expense paid conventions in paradisiacal locales, and prestigious studies that show it's for sure at least 1% more effective which makes it a game changer. And even then it's for insurance to cover.

Really cheap healthcare is really hard to get because other reasonable economic factors still play a role. People want more of it because it's cheap and it still costs real money to provide so there's only so much budget for it. But if you manage to get it you will be way ahead. The big factor is that cheap healthcare weeds out practitioners who value your money more than your humanity. Maybe you'll also weed out a great doctor who charges a lot because he's so good, though.


Hope that you put your home and all your assets in a trust for your kids before you got treatments. You can declare bankruptcy in Texas or Florida and still keep your house, but I guess that only works if you are still alive . . . after you die the medical community just files suit to steal all your assets.


I've heard about great successes with animal based ketogenic diets, and fasting. There's a clinic in Hungary that treats and (tries to, despite apparent censorship), publish research: https://www.researchgate.net/publication/331812176_PALEOLITH...

Hope you'll find something that works, even if only augmenting your current treatment


What’s the argument for this exactly? Most of what I’ve heard about keto diets involves leaving blood sugar levels dangerously low for long periods of time by forcing your body into its weird starvation mode. That maybe sounds like something that could help with cancer because of its relationship with metabolism but the whole thing sounds like a stretch to me.

On the other hand those are all feelings and I’m not trained in medicine.


Most of what I’ve heard about keto diets involves leaving blood sugar levels dangerously low for long periods of time by forcing your body into its weird starvation mode.

That's a gross mis-characterization of keto diets, at least when done properly[1].

Up to 20g of net-carbs (ie: non-fiber) per day. The intention is to moderate your insulin response, which impacts other hormones and, for weight loss, switches your fat cells to be able to release fat for energy instead of storing fat. That level of carbs are more than adequate to maintain necessary blood sugar levels for your body's needs.

There's no "weird starvation mode". Lowering your carb intake and moderating your insulin response causes your body to stop the "easy" burning of carbs for energy, and to switch to burning fat (from your food first, fat cells second) for energy. A big misconception about keto is that you have to eat a lot of fat; if you're trying to lose weight that's not true. You need to consume enough fat to keep your calorie intake from being too low (otherwise you do get into a starvation mode which lowers your metabolism), but low enough so that your body needs to get fat from your fat cells to make up its energy needs.

All that said, I have no idea if keto helps with cancer at all. It almost certainly has no direct affect. If there's any benefit, I would guess that it's related to the hormonal and metabolic impacts of fat-burning rather than carb-burning, or the reduction of systemic inflammation that most people on extended keto diets experience.

[1] https://www.reddit.com/r/keto/wiki/faq


I'm not a professional researcher on this topic, just an passionate observer and n=1 having healed an "Incurable" autoimmune condition using a carnivore (ketogenic) diet.

The rationale to put it shortly is that cancer (amongst other modern disease epidemics) is a mitochondrial disease, that most cancers have damaged mitochondria and can't process ketone bodies. Ketogenic metabolism is perfectly healthy and most probably the default state for human biology. I won't go into details in this reply, but my personal experience and that of thousands of others attests to this.

The rationale for an animal (and animal fat) based diet is more complex, but it revolves around the fact that all plants contain compounds that damage the intestinal lining to varying degrees. This leads to a cascade of events in which the immune system devolves into a diseased state that leads to the wide array of chronic illnesses that we see today. Chronic inflammation disturbs the whole system, often includes neuroinflammation, which itself causes depression and exacerbates stress, worsening the condition further.


First, check the warburg hypothesis: https://en.m.wikipedia.org/wiki/Warburg_hypothesis

Cancer cells rely much more on glycolysis than oxidative phosphorylation (respiration, basically breaking down sugar with oxygen). You get a net of two molecules of ATP from glycolysis compared to 30 or so from respiration, so you can expect that cancer cells need much more sugar than normal cells just to survive. https://en.m.wikipedia.org/wiki/Cellular_respiration

Second, glucose competes with dehydroascorbate (DHA, oxidized vitamin c) for glut1/3 transporters. DHA gets transported into cells (in particular RBC's) to be reduced back to the anti-oxidant form by glutathione: ascorbate. Then that ascorbate molecule can remain in the cell acting as an antioxidant or be pumped back out of the cell to the blood, etc.

If DHA doesn't make it into a cell quickly it gets hydrolyzed and excreted and you lose that molecule of vitamin c. So chronically lower blood sugar is expected to conserve your vitamin c and allow higher ascorbate levels, especially within your cells.

This can have all sorts of beneficial effects. Strengthened collagen makes it easier for a tissue to heal/encapsulate the cancer and harder for it to metastasize, quenching free radicals can prevent damage to surrounding tissue, etc.

But also, cancer cells accumulate more iron than normal cells: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983609/

Ascorbate can also reduce Fe3+ iron to the Fe2+ form. That Fe2+ iron can then undergo the fenton reaction to form free radicals: https://link.springer.com/article/10.1007%2FBF03033342

Those free radicals can go onto to kill the (high iron) cancer cells. For this reason vitamin C kills almost all cancer cell lines in vitro at doses that do not harm normal cells: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516281/


Of course we are talking about cancer here, but for healthy people I don't think the blood sugar levels during ketosis are ever considered dangerous. And even though you aren't eating much carbs, your blood sugar may never get low at all, because you aren't burning them very much either.

As for keto diets and cancer, there's been a lot of studies claiming all kinds of things. I have trouble trusting diet related studies, as they constantly contradict each other and probably have far too few subjects versus the number of variables, which they often can't control. But as for the theory, I think at least for particular cancers it is believed they need sugar to grow, so can be starved by a keto diet.


As someone who works in healthcare, I don't disagree with the entire sentiment here, with the exception of screening. In my opinion, it would be simpler and more cost effective to monitor cancerous and precancerous indicators rather than immediately go for surgery/treatment. Most people probably freak out if you tell them they have a golf ball sized growth on their kidney though.


And then to take it one step further: focusing on prevention and being proactive, which may require more research funding, however that no one can or is widespread promoting a solid set of known practices to reduce cancer is a problem.


> however that no one can or is widespread promoting a solid set of known practices to reduce cancer is a problem

My friend at American Cancer Society would take issue with that statement. He flies all over the world educating public health officials about how to fight tobacco use.

Tobacco by itself is a huge cause of preventable cancers.

The next big one is sun exposure, so ACS also promotes proper sunscreen use (and avoidance of tanning beds).

The ones caused by genes and random mutations are also a large percentage, but you can't teach people how to avoid those.

People should get radon tests in their home as well. Most lung cancer is either due to tobacco or radon.

After that, there isn't much advice specific to cancer: eat moderately and exercise.


There is a skin cancer pandemic since health authorities started warning people to avoid the sun. It is found mostly in people who avoid/block the sun and not eg people who work outside everyday.

https://www.ncbi.nlm.nih.gov/pubmed/20231499

https://www.ncbi.nlm.nih.gov/pubmed/20541680

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1694089/

Also, tobacco smoke seems to be an exceptionally weak carcinogen. It is near impossible to get it to cause cancer in animals (while eg, radioactive dust easily does so). Think about it, people expose themselves almost 24 hrs per day for decades and still less than 25% get lung cancer.

https://www.ncbi.nlm.nih.gov/pubmed/15765916

https://www.ncbi.nlm.nih.gov/pubmed/29370344


I'd be hesitant to call tobacco smoke a weak carcinogen, especially when there are mutational signatures known to be associated with exposure to it.

But by and large, it is a numbers / probability game. You could be exposed to a carcinogen routinely for your entire life and not have any problems. Or, you could be exposed once, and have it hit is just the wrong place. I'd say a 25% incidence rate is pretty high, and not something that I'd personally like to risk. Lung cancer rates are still high, with smoking being the primary risk factor. So, are you seriously going to argue that smoking is not something to avoid?

Skin cancer is another... the known primary risk factor is sun exposure (again, with a known mutational signature associated with UV light). Many people who avoid the sun likely already know that either a) they have a family history of skin cancer or b) they have sensitive skin that burns easily. Either of which is a good reason to avoid sun exposure.

Given the above and other comments in this thread, I'm struggling to figure out what your point here is. You keep attaching a lot of Pubmed links, but frankly, in this case at least, they aren't all that compelling and don't even begin to approach a scientific consensus. You're just cherry picking random articles.


> You keep attaching a lot of Pubmed links, but frankly, in this case at least, they aren't all that compelling and don't even begin to approach a scientific consensus.

Which of these statements do you find controversial?

1) Skin cancer rates are rising dramatically

2) Until very recently (in the last ten years) the vast majority of sunblock was transparent to UVA but opaque to UVB

3) Blocking UVB prevents the skins normal darkening and thickening response as well as sunburn

4) UVA penetrates the skin deeper than UVB and causes damage to the DNA in the cells there

5) Damage to the DNA of skin cells is associated with skin cancer

6) Without sunburn to warn people their skin is damaged they are more likely to leave their skin exposed to the sun.


You think there is no consensus that skin cancer rates are skyrocketing?


> It is found mostly in people who avoid/block the sun and not eg people who work outside everyday.

This is classic confusion of correlation and causation.

People with lighter skin are aware of the increased risks of sun exposure and avoid/block the sun. Further, a lot of outdoor labor in the US is now done by people with darker skin (e.g. immigrants from Mexico with indigenous heritage).

Finally, sunblock isn't perfect. At-risk people can reduce, but not eliminate, the chances of developing a tumor. European-descended people are living in climates far south of where they evolved light skin, so cancer is inevitable.

> Also, tobacco smoke seems to be an exceptionally weak carcinogen

So is radon. What's your point? It may be weak, but it causes a massive number of avoidable tumors and deaths per year.


There was no confusion of correlation and causation in my post. It is a clearly stated correlation.

Broad spectrum sunblock may be less than perfect, but until recently all sunblock was transparent to UVA. It blocked UVB which prevented the natural sunburn/tan/thickening response without preventing the DNA damage.

Given the huge growth in skin cancers since people started wearing sunblock it seems likely that it was actively harmful for this reason.


>After that, there isn't much advice specific to cancer

There's HPV (human papillomavirus) that causes cervical cancer. It's preventable by a vaccine (e.g. Gardasil).

Helicobacter Pylori can cause stomach cancer. If detected early it can be eliminated with a two week antibiotic treatment.


Yeah, but we are still missing those inputs form the previous life years that lead to cancer, ie exposure to chemicals through work, diet, etc as its the environmental load that matters here combined with the genetics profile of course


This article is absolute 100% bullshit.

-Metastatic melanoma: used to be lethal, now 50% cure rate.[1]

-Non small cell lung cancer: same, now around 25% [2, 4]

-Breast cancer used to have a terrible prognisis, now 75% survive. [3]

-Not to mention the myriad of blood cancers with new, strong, cell therapy treatment options with 40-50% durable cure rate.

I don't know this person, but seriously, whoever he is, fuck you dude. Millions of us work day and night trying to improve care, and 99% of us arent getting rich.

[1] https://www.nejm.org/doi/full/10.1056/NEJMoa1709684

[2] https://www.nejm.org/doi/full/10.1056/NEJMoa1801946

[3] https://www.breastcancer.org/research-news/20100930

4. https://investors.merck.com/news/press-release-details/2019/...


He also wrote an article called the "Death of the Proof" that was widely rejected by mathematicians and was also mostly hog wash.

He seems like a guy who likes to make edgy but wrong statements.

https://blogs.scientificamerican.com/cross-check/the-horgan-...


This is far from the first time, so let me state this more explicitly: John Horgan is a provocateur with no knowledge of any field, whose only claim to fame is that he is so breathtakingly and publicly wrong that he gets people with real expertise to engage with him. Then he disingenuously frames the result as a real intellectual controversy with him at its center.

He is one of the top reasons I don’t take anything from Scientific American seriously anymore, and a great example of how the incentive structures in science popularization ruin it. I find that I can tell how savvy an online community is by how much it likes his work.


> Mathematicians named a mathematical object after me. It’s called the Horgan surface, or, alternatively, Horgan non-surface. The term was intended as an insult, but I’m honored anyway.

Neatly summarizes this guy’s motivation for writing provocative bullshit. To him, infamous == famous.


> He is one of the top reasons I don’t take anything from Scientific American seriously anymore

Some people have started calling it "Two Lies, One Title".

It's turned into the BuzzFeed of science journalism.


I knew I kinda knew that name! Good reference, thank you!


> Breast cancer used to have a terrible prognisis, now 95% survive.

5 year survival rates may just mean we're now scanning a huge population and spotting many cancers much earlier. What's happened to the all-cause mortality rate for breast cancer patients? Has that all that scanning and treatment increased length of life?


I really thought I'd read (summaries of) careful statistical analyses that say this is why the medical community thought "early detection saves lives".

100% willing to be corrected by the many more knowledgable commentators, but this is an important question, even if the parent phrased it as just speculation.


Some parts of the medical community say "early detection saves lives" because they make their money from all the scanning and treatment.

https://www.harding-center.mpg.de/en/fact-boxes/early-detect...

https://www.harding-center.mpg.de/en/fact-boxes/early-detect...

Icon boxes can present the information in different ways: https://www.econlib.org/archives/2015/08/is_prostate_scr.htm...

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD...

> We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on total cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all‐cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).

> Total numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42), as were number of mastectomies (RR 1.20, 95% CI 1.08 to 1.32). The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data available in only two trials).

Screening often doesn't affect all cause mortality, but if you're screened you're significantly more likely to have treatment with all the risks and side effects that entails.

There are some screening programmes that work though. Cervical screening is important and does save life.


Thank you for writing a more concise version of what I tried to write below.


You made some very good arguments with solid information here. So much so that I flagged this article. Doesn’t seem what HN should spend its time refuting.


I flagged it as well an hour ago, I don't know why it's still up, probably the mods are not looking at HN right now.


Thanks!


Please provide sources so we can see where these numbers are coming from.


I'm out w my newborn but will do when I get back.


If I'm reading this right it looks like 3 yr survival was 30-50% in high risk melanoma patients in the late 1960s to early 1970s: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1344342/

That is pretty much the same as in your paper. Not sure how comparable those patients are though.


Thanks, do you have one for melanoma in mind for comparison to that study when you say "used to be lethal".


Ok, mostly there. Will try to find more.


You make no direct connections with the article, open with an absolute statement "100% bullshit" which can almost never be justified, and shortly describe yourself cursing at the author.

The links you added do not amount any sort of representative sample or review of the cancer treatments concerned. Of relevance to your own small selection of improved treatments (some of them decades old) the Oncologist interviewed in the article states:

> Trials have yielded improved treatments for childhood cancers and specific cancers of the blood, bone-marrow and lymph systems, Raza notes. But these successes, which involve uncommon cancers, are exceptions among a “litany of failures.”

Your comment is an exceedingly emotional and basic attack towards the articles subject and none of its content.


Ive seen medical attempt to sell me extra services within their hospital network with my kid. 2000$ to fix Tongue Tie with surgery. Laser procedure is 600$ and done at a dentist.

The ($200-300k/yr) physician said there was data surgery is better. So I looked it up, no data, and surgeons started using laser because it heals better. Upon confronting she said- if you ask a physician they will recommend a physician. (So factionalism?)

Why is this nonscience acceptable in medical?

On a different note, hospitals somehow get patients for non hospital needs.(disclaimer my wife owns her own practice and competes) For instance if you go to a hospital for physical therapy, you will likely have 1 Dr for at least 2 patients. You get 37 minutes of treatment because they can legally bill for 1 hour. At my wife's clinic, she treats 1 on 1, and sometimes sessions go over 1 hour.

There are no advantages of a hospital for this care.

I'm not sure if overregulation or lack of patient information is to blame. I'm horrified at the thought of being sick and dealing with our medical cartels.


This would be in the US I presume? Proponents of single payer focus a lot on the issues with insurance taking profits, but I think the real problem with capitalist medicine is that the skills needed for selling medical procedures and helping patients heal are not really compatible. Doctors being forced to sell their own services creates a perverse incentive towards the most expensive procedures, which unfortunately are often also the most risky.


That person is likely not in the US. We put the $ before the digits.


Well, this is one side of the discussion. While I agree to some extent, the author should also answer the question whether he honestly thinks he would have been better off 90 years ago if some cancer got detected with him in, say, 2 weeks from now (such things usually happen really fast).

You can of course take the stance that 90 years ago that cancer would have been misdiagnosed and left untreated and that 90 years ago he would have probably died of something else before that cancer would have got lethal. I personally rather prefer having the cancer cut out as soon as possible.

Also some arguments are not honest. It's right that e.g. most dead men have some form of undiagnosed prostate cancer, which they didn't notice. But screening programs usually are not designed for e.g. 90 years old people for who it probably doesn't make that much of a difference whether an early stage cancer gets diagnosed. Screening programs usually are for younger people who will most likely get old enough to benefit from an early diagnosis.


> Screening programs usually are for younger people who will most likely get old enough to benefit from an early diagnosis.

You say "likely". But the problem is you don't have evidence. Noone has shown that these screening programs do have these benefits [1]. If they have I don't think anyone would argue with that.

The tricky issue is: Actually showing the benefits of these screening programs is hard. It requires large-scale studies with longterm followup. It's expensive. But it nevertheless should be done.

[1] https://www.bmj.com/content/352/bmj.h6080


People have done studies like you propose, but long term studies always lag improvements in treatment. You can’t see 20 year mortality statistics for 2020’s cancer treatment options until 2040.

CDC supports screening for breast, cervical, colorectal (colon), and lung cancers

Screening for ovarian, pancreatic, prostate, testicular, and thyroid cancers has not been shown to reduce deaths from those cancers. The USPSTF found insufficient evidence to assess the balance of benefits and harms of screening for bladder cancer and oral cancer in adults without symptoms, and of visual skin examination by a doctor to screen for skin cancerexternal icon in adults. https://www.cdc.gov/cancer/dcpc/prevention/screening.htm

PS: Showing differences in overall mortality based on differences in treatment for an uncommon disease requires truly massive study’s. Failing to show a correlation is expected with noisy data and insufficient sample sizes.


The problem also is that diagnosis doesn't stop progressing. Today's opponents to cancer screening often argue with data from the 1990s. On the other hand proponents often refer to data of underpowered, badly designed trials.

Also, there exists no real guideline as to what would be "sufficient evidence". How much better would the survival of screening participants would have to be? In exchange, how much pain may be inflicted on people who get false-positive results. This discussion is extremely difficult. And once you are in the situation that you or somebody close to you get's diagnosed with cancer, it becomes really difficult to deal with arguments like: "On average the whole population does not benefit from you having diagnosed your cancer early so that after some small surgery, you'll continue living as if nothing had happened."


>the author should also answer the question whether he honestly thinks he would have been better off 90 years ago if some cancer got detected with him in, say, 2 weeks from now (such things usually happen really fast).

No, the hypothetical situation in your question misses the gist of the article: the hypothetical situation should still be in present day but with much less funds having been spent on cancer research.


You don't get good cancer diagnosis without funding. You don't get neoadjuvant therapies without funding.


I was really hoping for a strong conclusion to this article - a powerful answer to the obvious question of 'so what now?'. After all, the author has just spent a lot of words tearing down the (generally well-meaning) attempts of scientists (and others) to prolong the lives of people who are diagnosed with cancer.

But all we get at the end is "Conservative cancer medicine, as I envision it, would engage in less testing, treatment, fear-mongering, military-style rhetoric and hype. It would recognize the limits of medicine, and it would honor the Hippocratic oath: First, do no harm.".

Fuckin' really? No details, no data, no actual suggestion (or idea?) of how to actually implement this? No analysis of how (or even whether) this will help people?

And of course, let's ignore the fundamental hypocrisy here: having just spent an article discussing how shit doctors (apparently) are at doing the best thing for their patients, he apparently wants doctors to be the ones in control of this new, 'do less' approach? Fucking clueless clickbait blog nonsense - the Scientific American should be ashamed that this made it through their editorial process as is.

-

Also, let's examine these two sections:

"But one study found that 72 new anticancer drugs approved by the FDA between 2004 and 2014 prolonged survival for an average of 2.1 months. A 2017 report concluded that “most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points,” including survival and quality of life.

Medical conservatives happily adopt new therapies “when the benefit is clear and the evidence strong and unbiased,” the authors emphasize, but many alleged advances “offer, at best, marginal benefits.”"

Who, exactly, is going to serve as the judge and jury for what constitutes a sufficient improvement in clinically relevant endpoints? Should that role be given to "medical conservatives" - i.e. people who the author thinks are more trustworthy than people who disagree with him?

(PS I fully understand the application of cost:benefit analyses to new drugs - and maybe this is a direction that the US needs to go. But note that the author's conclusion section didn't even touch on this as an option.)


The authors worried that “the FDA may be approving many costly, toxic drugs that do not improve overall survival.”

I don't think they purport to serve as or appoint anyone to serve as judge and jury for "sufficient" improvement. The concern is the approval of drugs which provide no improvement.


That's not how I read it, although to be fair, it's not written clearly. This is the full quote from the article:

But one study found that 72 new anticancer drugs approved by the FDA between 2004 and 2014 prolonged survival for an average of 2.1 months. A 2017 report concluded that “most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points,” including survival and quality of life. The authors worried that “the FDA may be approving many costly, toxic drugs that do not improve overall survival.”

Therefore, the implication is that drugs which prolonged survival by an average of 2.1 months (which was the FDA's track record for approvals between '04 and '14) are not sufficiently "clinically relevant" to justify approval (presumably the 2017 report quoted from includes these drugs).

Therefore the question remains: if small but incremental improvements (av 2.1m) aren't sufficient to warrant approval, what level of improvement would be sufficient? And who are the right people to draw this rather important line in the sand?


Living 2.1m longer may not be seen as an advantage if those two months are spent in severe pain trapped in a hospital bed suffering from a wide range of serious side effects.

We need to talk about death and we need to talk about what people want when they die. A few people do want to struggle and gain every extra day they can no matter how painful that's going to be for them, but that's not what most people want.


I agree with your sentiment, but that's a bit of a straw man you're building there. The FDA would require that those two extra months usually aren't spent suffering unbearable additional side effects from the treatment, and it would also be fairly uncommon for such patents to be "in severe pain trapped in a hospital bed".

In contrast, if you've got (say) three months to live, the prospect of an extra few months with a reasonable quality of life, if probably something many people would take.


> The FDA would require that those two extra months usually aren't spent suffering unbearable additional side effects from the treatment,

I can't speak about FDA, but I can speak about NICE and the Cancer Drugs Fund.

NICE was set up to look at the cost effectiveness of medications and treatments. They were refusing to recommend new cancer drugs. This was politically tricky, so the Cancer Drugs Fund was set up to provide novel meds.

We spent over £1bn on it, and most of the drugs provided no meaningful benefit and caused harm. https://www.bmj.com/content/357/bmj.j2097


I'm pretty sure two months is statistically insignificant in this context to even claim there are two months.


That can't be supported, given that the two months in question is only a median from a review (of FDA drug approvals for solid tumors from '02 to '14). https://jamanetwork.com/journals/jamaotolaryngology/article-...

You'd need to explore the data behind the individual approvals to comment on statistical validity. But without going that deep, you can be assured that the FDA is generally pretty conservative, and employs very robust statistical methodology.


More than 1.7 million Americans were diagnosed with cancer in 2018, and more than 600,000 died.

We don't know how many patients received the 72 drugs approved over a ten year period but we do know the potential customer base for the drugs is massive. Millions of people could have taken the drugs, you could easily get a statistically significant result.


Perhaps the difference of our reading can be down to a difference in our interpretation of "average". It is unhelpful and imprecise allowing a variety of interpretations. I have interpreted it to be an average with a high variance - perhaps as much as 3 months. Thus some of the drugs decrease survival on average.

It seems that maybe you are considering a smaller variance with all the drugs tightly clustered around the 2.1 month average where the central question becomes - what's the cutoff and who decides?

As to who decides where the line should be drawn in the US it is the patient and in the UK it is the government (NHS). Ideally the patient should give informed consent for a treatment regime, that means realistic assessments of likely outcomes sans hype.


(Apologies for the delay in replying to you.)

I was able to access the paper in question, and of the 71 trials included in their analysis, two trials reported a negative overall survival (OS) outcome (-0.3m and -0.6m) and one trial reported exactly 0m overall survival gain. There were also 23 trials (I think - quick eyeballing) where the overall survival gain wasn't available or reported. Everything else had a positive overall survival benefit reported.

In most cases (2/3 cases with a negative or null survival benefit reported, and a majority of the cases where no survival benefit was reported) there was a positive improvement reported in progression-free survival (PFS).

So with the exception of a single case (Premetrexed, approved in 2008 for 1L NSCLC with 0m PFS benefit and -0.3 OS benefit - maybe it was better tolerated than the comparator??) there's seems to be a positive benefit to be found somewhere, small as it may have been in some cases.

And yes, it's essentially a data-set with a lot of clustering of OS benefit around a low single-digit number of months, with a few higher outliers.

EDIT: FWIW, it would also be very uncommon (as borne out by the dataset) for FDA to approve a drug which didn't offer a clear statistically-significant improvement in (usually) OS or (more rarely) PFS.


> As to who decides where the line should be drawn in the US it is the patient and in the UK it is the government (NHS).

No, this is wrong. UK patients have the same access to private healthcare as Americans.


Terminally ill boy denied 'potentially life-saving' treatment by NHS 'would be given it in any US hospital'

https://www.telegraph.co.uk/news/2017/04/03/terminally-boy-d...

The NHS decides what's necessary care and what's not, then they're supported by the courts. The illusion of "same access as the US" was shattered by Charlie Gard when reality collided with our ideals.


In the UK: The doctors come up with a plan. The parents disagree. The doctors need to go to court to get a ruling.

In the US: The doctors come up with a plan. The parents disagree. It is the parents who need to go to the courts to get a ruling.

Charlie Gard's case has absolutely nothing to do with cost. In the UK children are humans and humans have rights, and those rights are protected by the courts. Parents do not get to own children as possessions. The courts will focus on the child's best interests, because of the Paramountcy Principle which flows from Article 3(3) of the EU Treaty and Article 24 of the Charter of Fundamental Rights of the European Union, which flows from the UNCRC article 3(1). Charlie Gard's case is about someone who cannot make a choice for themself, and the courts focussing on that person's best interests, not on the interests of that person's relatives.

Charlie Gard had RRM2B MDS. This has fewer than 50 cases worldwide. There is no cure. There is no treatment. The discussion is whether to allow him to die with pain relief, or allow medical experimentation that has no hope of success but which will cause pain. Unsurprisingly the courts decided it was in his best interests to be allowed to die with pain relief.

http://blogs.bmj.com/medical-ethics/2017/07/07/never-let-an-...

You may wish to read the judgments, because almost everything written by the US press was wrong.

https://www.judiciary.uk/judgments/great-ormond-street-hospi...

https://www.judiciary.uk/judgments/great-ormond-street-hospi...


> After all, the author has just spent a lot of words tearing down the (generally well-meaning) attempts of scientists (and others) to prolong the lives of people who are diagnosed with cancer.

You are showing massive bias here. It's ok to criticize science, it's normal and necessary even, but to "believe" in science and "well-meaning" of scientists and trust their opinions and conclusions is not, it's harmful, like in this case causing literal unnecessary suffering of real people and robbing them and their families while they are.


To answer your point directly: for sure, I have a bias that the majority of scientists who work in cancer research generally mean well. But holding a positive view of (bias towards?) such people and their motives doesn't constitute not being willing to criticise science?

--

In this case, my frustration is that the author isn't intelligently criticising the science; I totally agree with you that science (and related issues, such as FDA approvals, or cost:benefit analyses of drugs) should of course always be open to exploration and criticism.

Instead, he's written an opinion piece masquerading as science, by using a variety of supportive quotes and excerpts to build a general case that cancer is big business, that there's a kind-of dark nefarious industry behind it all, and that people who work in this area are complicit in hurting patients with cancer. (It feels one step away from a conspiracy theory.) By confusing totally different topics (e.g. marketing of cancer drugs, vs. value of screening, vs. cost:benefit of cancer treatments, vs. side-effects of cancer drugs, etc.), by paying insufficient attention to any of them, and by employing such a broad brush, he turns a set of highly complex topics into a pointless oozing vat of negativity, possibly aligned with his workd-view.


Patient schnoz blasting right on undressed port catheter? Tsk tsk.


I'm not in the medical field, but I never wore a mask when my port was accessed (the nurses did). Sure, less exposure is better, but could you explain further?


I'm not in the medical field either, but based on my experience patients are either asked to wear a mask or turn their head away while the port is being accessed until it's removed or there is a dressing in place.

Step 7 : https://www.specialove.org/wp-content/uploads/joomla/58f-PRO...


I am disappointed in Scientific American for publishing such shoddy work. Anyone can cherry-pick one piece of evidence per point to make themselves seem well supported. That doesn’t mean they are.


It’s the narcissistic executives that lead a decent amount of the cancer medicine companies focusing on their next round of golf or nice car. I thought medicine would be different but it’s almost the exact same.


Cancer is not a disease, but a state of overall body deterioration. You can't fix it; only the body can fix itself.

Stop attacking it with carbs and plant oils, and give it the fuel it needs: unprocessed animal protein and fat.


A broken arm is not a disease, but a state of body deterioration. You can't fix it; only the body can fix itself.

Stop attacking it with splints, plaster casts and slings, and give it the fuel it needs: unprocessed yellowcake Uranium.


Can't believe I missed this opportunity.

...and give it what the body craves: Brawndo, its got electrolytes.

That would have been way better.


It is a disease and survival has dramatically increased because of amazing progress in treatments. Just look at the recent drop in cancer mortality in the US.

It is incorrect and irresponsible to blame people who get cancer for eating badly etc. Sometimes things go wrong at a cellular level and cancer happens.


Did you read the article? It states the drop in cancer mortality is largly due to the fall of smoking.

'A 2006 analysis concluded that “without reductions in smoking, there would have been virtually no reduction in overall cancer mortality in either men or women since the early 1990s.'


There's no real drop, but number manipulation. They just label you as "healed" if the tumor doesn't return after a some short period of time, which gets shorter by the year.

Actually mortality rates are at all times high, globally.


Are you referring to the shift away from using overall survival to progression free survival? If so I agree that this rubbed me the wrong way as well.

However if one looks there has been tremendous progress in some cancers. As an example CML went from a swift death sentence to something approaching a chronic condition.


That’s because everyone dies! The article avoids mentioning that cancer rates have risen as other causes, particularly infections, have declined over many decades. The average lifespan has increased globally. In developed countries this is largely due to improvements in cardiovascular drugs/treatment and cancer drugs.

The standard survival rates are quoted as 5 year survival unless the cancer is particularly aggressive eg pancreatic. The statistics around cancer are very high quality and public in most countries. However, I suspect data will not influence your view.


Counterfactual : Steve Jobs


Is this based on fact it opinion?


The entire medical field is based on opinion and wizardry. We're sicker and weaker than ever. I've healed myself from various conditions by going carnivore.

Take it or leave it.


There is a lot of snake oil, from crackpot websites to overhyped university press release. Anyway, two clear points where medicine work:

https://en.wikipedia.org/wiki/Penicillin

https://en.wikipedia.org/wiki/Smallpox#Eradication


Full disclosure: I have not read the article yet but gathered a sense of it from the comments here.

I like your citations. They make me think about a recent radio interview in Canada where an MD was discussing cervical Cancer. He would not say that vaccination for HPV prevented Cervical Cancer. He would only say that it prevented pre-cancerous lesions and Cervical cancer "is never seen without pre-cancerous lesions".

I can understand using scientific rigour to avoid jumping to conclusions. However it makes me wonder about Louis Pasteur and the discovery of micro-bacterial disease origins. Would he have said: "I can't say that these bacteria causes disease X but we have never seen disease X without the presence of these bacteria." ?

All that to say perhaps medical research has been going down the wrong path with Cancer. We have one clear case of viral "involvement". :-)

How big a stretch is it to extend research in that direction and look for more cases?


Virus that can cause cancer are known since 1908 in chickens and since 1964 in humans. More details in https://en.wikipedia.org/wiki/Oncovirus

But not all cancers are caused by virus. Probably some of the multiple toxic compounds in the smoke of tobacco is the most known case. Radiation is also a well known cause. Even more info https://en.wikipedia.org/wiki/Carcinogenesis


Excellent, so that would mean there is more research coming for other vaccines beyond HPV... ? I have not heard of any but it's not my focus.


From your wikipedia link, this technique sounds like a great way to find more cancer causing viruses.

"...developed a new method to identify cancer viruses based on computer subtraction of human sequences from a tumor transcriptome, called digital transcriptome subtraction (DTS)"

It's from 2008. There has been enormous improvements in DNA technology since that time.


Human digestive tract and limb power share is evolved around omnivorous diet.


> if 2,000 women have mammograms over a period of 10 years, one woman’s life will be saved by a positive diagnosis. Meanwhile 10 healthy women will be treated unnecessarily, and more than 200 “will experience important psychological distress ...

I have never understood this argument.

I’d rather be incorrectly told I had terminal cancer 100 times over, than not be told and... die. You know what’s worse than psychological distress? Dying. You knowing what’s worse than an unnecessary surgery? Dying.

This is so obvious, I struggle to understand how this “overdiagnosis” argument even got started.


The problem is nobody is telling you the truth or providing a way to make an informed decision. And not just because they want to take your money, but also because they themselves simply don't know how to make such decisions. They pretty much just try various things on real people to see if they work or that can confirm the hunches they have for further interventions, ignoring consequences of doing any of it.

Like in your particular example, every unnecessary surgery actually increases your chances of dying during surgery or sometimes after it, not to mention the chances of crippling you forever, but you don't know what those chances exactly are and worse, you are assuming there isn't such risk, while it's crazy high. So high, that 100 times false positive rate absolutely makes it a no brainer to never undergo such diagnosis, it pretty much guarantees to make things worse for or kill a lot of people.

And yet nobody will give you the numbers to make a rational decision.


I met someone who went for a checkup and they convinced him to get a screening colonoscopy. It was clear but a few months later he started having problems and went back. Then they told him he had colon cancer caused by damage to the tissue during the colonoscopy.


Watching Eric Weinstein's The Portal episode #18 yesterday - https://www.youtube.com/watch?v=QxnkGymKuuI - where he presents the DISC (Distributed Idea Suppression Complex), made me frame this in a different way: what questions does the cancer treatment industry avoid? Why aren't all cancer companies, organizations, also researching or putting funding towards prevention? The answer is obvious to me, however why as society don't we require a sort of tax to counter (and fund) what the industry isn't aligned to do profits wise?




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