Comment by jacquesm | Hacker News Reader

Comment by jacquesm | Hacker News Reader

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Even 100% true positive rate would not guarantee improved patient outcomes with massive testing. This is grounded in a poor understanding of what improved patient outcomes are all about, which is fine with me but to see this so misunderstood is a bit disappointing.

Better tests do not automatically lead to better outcomes. They will lead to many more cancers detected, and they will lead to more interventions.

Just one example (there are many more): for many tumors the risk of the operation to excise it already outweighs the risk of the tumor itself leading to damage to the body.

The factors that govern whether an intervention is necessary are determined by the rate of growth, the risk of meta-stasis, the organ(s) affected, the stage the cancer is currently in (and here early detection would at least help to get a grip on that) and so on.

But once detected treatment is going to be the norm, and that's where the problem lies: treatments are not necessarily an improvement over having a mostly dormant cancer.

If you were to autopsy all of the cadavers from any given country for a period of time you would find a correlation with age and the presence of one or more tumors in that cadaver, even if the person never had symptoms and died of a completely unrelated cause. Treating all of these would have resulted in some of those people ending up in the morgue a lot earlier and having a reduced quality of life both from a medical and a mental health perspective.

Deciding to treat - or not - is not a simple matter.

Your point across this thread is weird because it's not the testing itself which is an issue (if we assume the testing has a negligible cost economically and is comfortable/easy for the subject).

We just need to improve the decision making after getting test results (one of these decisions is to decide to not do anything), and more data make improving it easier.

But tests do not have a negligible cost, have other costs besides the pure monetary value (such as occupying valuable lab time that could be spent on symptomatic patients instead), are typically not at all comfortable and easy because you'll be looking at a biopsy at a minimum (which again takes away valuable resources from symptomatic patients) and so on.

My argument is not about particular individuals, but about populations as a whole and wholesale screening of those populations. The consensus is that this does not lead to improved patient outcomes across that population, though in individual cases it may very well be the result.

My lay understanding of the current standard of care is very roughly speaking something like:

Patient exhibits symptom => perform a not-especially-invasive test Positive test result => invasive test like a biopsy Positive biopsy result => heavy-duty intervention (although I'm not focusing on this part of the chain in what follows)

Both testing and (certain) symptoms have predictive value, and don't completely overlap. So there's something like this going on:

P(actual problem|no additional information) = really really low, which is why they don't scoop out chunks of every organ to test "just in case" every time you go to the doctor

P(actual problem | [symptom AND positive test result]) = generally high enough in at least some cases to justify the risk of the biopsy, which is why it's the standard of care

P(actual problem | just symptom) = probably not super high, which is why the tests are developed

P(actual problem | just a positive test result) = substantially lower than P(actual problem | [symptom AND positive test result]), so in the general case the balance of risk no longer favors the biopsy

In the broadest of strokes, is there anything I've just said that you substantially disagree with?

No, there isn't, though it is probably important to point out that age, genetic disposition and gender are a big factor in selecting what kind of test and if positive what kind of treatment - if any - will be administered and that this is as you correctly identify on symptomatic patients only which raises the base rate in that population (the population of symptomatic patients) tremendously.

And that's exactly where the issue with indiscriminate asymptomatic testing lies, that requires much higher quality tests than the ones that can be used in a diagnostic setting once a patient is symptomatic.

To add one more unpopular bit of data to all this: there is some evidence that the indiscriminate testing for certain cancers has gone too far and that it no longer is a net positive. But in the presence of certain mutations those tests are extremely valuable.

https://www.statnews.com/2018/01/01/cancer-screening-misled-...

Biology is messy, and it is quite hard to state up front whether or not a test or a treatment - even if in an experimental setting it is working - will still be a gain if rolled out in a different setting or application. Hence all the trials and studies, that's the only way to really get a grip on this.

I'm quite curious what the outcome of the large scale test the article refers to will be.

>> treatments are not necessarily an improvement over having a mostly dormant cancer.

This is true today.

But if we could detect cancer at a really early stage, relatively reliably, maybe this means we could develop new and effective treatments that are low risk and low on side-effects ?

And if we had that, early cancer detection will also have a totally different meaning, so that could help with the mental health aspect too.

We could develop those treatments irrespective of early detection, there are plenty of examples of early detection of cancers today to make that feasible, this does not depend on a new test regime.

You may know more than me about medicine, but when it comes to allocating resources, I know just as much if not more than you.

If we start to test more, and understand the magnitude of the problem better (despite false positives/negatives) we can better allocate capital to solving this problem.

Sure, "cancer is horrible, we should already allocate as much capital as possible" but this just isn't reality. As soon as the addressable market for early-detected cancer treatment goes from X per year to 100X per year (and 1,000X or 10,000X is "even better"), big pharma has more motivation to actually R&D safe treatments for early-detected cancers.

Not testing more to detect cancer early is silly, if only from the perspective of capital allocation.

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