Comment by abcc8 | Hacker News Reader

Comment by abcc8 | Hacker News Reader

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Yes, the positive predictive value of the test may be low, with the PPV being equal to the number of true positives divide by the number of true positives plus the number of false positives.

Since this test is designed to identify cancer very early, a likely solution to the low PPV problem would be to re-test the individual, perhaps even multiple times. The likelihood of multiple consecutive FP test results, barring a biological reason for the FP, would at some point warrant a more accurate test, be it a screen or diagnostic test depending on tumor type. Also keep in mind that the PPV of the test would increase with a person's age - an 80 year old is at a greater risk of developing cancer than is a 30 year old. This test would also be useful for people with hereditary cancer syndromes.

The cost benefit would be huge - imagine if everyone could identify their cancer 6 months or even years earlier. Mortality would greatly decrease, as would spending on treatments, etc.

"barring a biological reason for the FP"

I think that's an unwarranted assumption. Sure, another source of false positives is contamination or user error even, but other than that most FP are indeed due to a (usually unknown) biological reason. I'm reminded of a friend that was just positive she was not pregnant. She tested herself three times with three different pee stick brands. She was wrong. They all use the same chemistry, and for some reason something in her body interferes with those tests.

The cost benefit for someone with a cancer diagnosis could be huge. But for the people with false positives, that could also be very harmful to people. A (false) cancer diagnosis would be incredibly stressful.

It’s tricky to find that balance.

This test is a screening test and thus can never be used to diagnose someone. Only a diagnostic test can be used to diagnose someone.

Screening tests like these will represent a paradigm shift in cancer surveillance and as such will require those administering the test, most likely a pcp, to properly educate each patient about what the test results mean and what steps should be taken next.

This seems like a failure in how test results are communicated to patients. Patients should just been told that they have been "flagged for further testing", rather than being told they have tested positive for cancer.

And how would that conversation go?

"You've been flagged for further testing."

"Why?"

"Um..."

"Didn't I just take a cancer screen? What was the result?"

"Ah..."

"Level with me, doc. Do I have cancer?"

"Well, [brings out probability textbook] you see ..."

So I have a real issue with not just telling the patient flat out that their test results indicate a high risk of having cancer and they need to be tested again.

As a society, we're just getting too used to accommodating people's ignorance about statistics and science. Where does it end?

Do we have to really have to give up promising therapeutics and diagnostic tests because we're afraid people's feelings will be hurt?

Yeah, I really hate it when people say what sounds like, "We recommend against even trying this test because people are incapable of responding appropriately to the answer."

It shouldn't even be that hard to state. "X% of people your age [+ whatever other factors they're using for a reference class] have [type of] cancer. Based on that and your test results, there's a Y% chance you have that type of cancer." Forgive me if I'm too disconnected from the average person, but is that too difficult to understand?

> So I have a real issue with not just telling the patient flat out that their test results indicate a high risk of having cancer and they need to be tested again.

The problem is that "tested again" has its own complications.

This is not theoretical. Part of the reason for updating the breast cancer screening guidelines is the fact that biopsies to confirm were causing more problems than the "cancers" they were finding.

Medical probabilities are tricky things.

You mean that the test physically caused a disorder in the patient because of a side effect, or that there was a problem in the patient’s attitude or emotional response? Because those are very different failure modes.

In one case the patient’s attitude about the test is not the determining consideration. A perfectly stoic and rational patient would be just as vulnerable to the side effects as anyone else.

A biopsy causes complications up to and including the death of the patient (secondary infections, etc.).

A biopsy is the next step to confirm "cancerous/non-cancerous" after a mammogram screen gives a "positive" result.

The problems with the screening is that once a "positive" comes up on the screen most patients cannot stop themselves from going to the next stage even if the probabilities don't warrant it.

The only medical "solution" was to decrease the frequency of screenings and raise the age at which first screening should occur.

Hmm, is that a situation where there is no appropriate action to take, regardless of the outcome of the screen? If that were the case, then there would be no point in doing the screen even if all actors were fully rational. But I'm guessing it's more like, the correct action is to wait N months and do a followup test.

Does it not work to say "If we take a biopsy, assuming normal treatment plans and outcomes for someone in your reference class, there's a 0.1% chance the biopsy kills you, and a 0.05% chance it saves you from cancer compared to the plan I'm recommending", or whatever the truth is?

(If the next possible step is a biopsy, under what circumstances does the calculus imply one should do the biopsy? When the screen results look sufficiently bad? Then maybe they shouldn't be presented as a binary "positive"/"negative".)

> Does it not work to say

No. It does not.

A diagnosis of "you might have cancer but the probability is low and we should just watch it" is not something that most people can psychologically take.

For more than half of the population, that kind of understanding is simply untenable.

And, even for people I knew who could understand it, several of them had so much anxiety that it drove their blood pressure up and it was better to just go get the biopsy so they didn't wind up with a stroke or heart attack.

In addition, "mortality probabilities" are a lot harder to psychologically absorb when you are 50 than when you are 20.

By the time you are 50, you've probably had more than a few of your friends and family in a coffin from a "low probability event".

Emotions are difficult. At some point, I will get diagnosed with a positive prostate screen (practically all men who live long enough do) that will almost certainly be "We should keep an eye on it." I hope I can weather it with the aplomb of my engineering background. We shall see.

Upvoted, but I remain skeptical. "You might have cancer but the probability is low and we should just watch it" is true for everyone who hasn't been screened, just the "might" is somewhat higher for those with a bad test result. Benign-looking moles on your arm could be cancer. Things you can't see or feel in your organs could be cancer. Also, plenty of other things could kill you practically without warning—heart attack, stroke, car crash, and the chance of the first two (and cancer) goes up over time. It seems to me that people have to come to terms with these things eventually, and "you have a low probability of having this type of cancer" just doesn't seem that different to me (perhaps it's best phrased as "you have an x% chance of being killed by this cancer"). If you've seen several people respond badly despite understanding probability, well, it's hard to argue with that, but I can't help wondering if it's fixable through slightly better communication or education.

Doing some reading about prostate cancer specifically, it seems like it actually is of the form "there is no appropriate action to take, regardless of the outcome of the screen"—or at least it's close enough that some experts think so. "In 2012 the United States Preventive Services Task Force (USPSTF) recommended against prostate cancer screening using PSA.[39] As of 2018 a draft for new recommendations suggests that screening be individualized for those between the ages of 55 to 69. It notes a small potential decrease in the risk of dying from prostate cancer, but harm from overtreatment." And: "A study in Europe resulted in only a small decline in death rates and concluded that 48 men would need to be treated to save one life. But of the 47 men who were treated, most would be unable to ever again function sexually and would require more frequent trips to the bathroom." https://en.wikipedia.org/wiki/Prostate_cancer_screening#Guid...

> "Didn't I just take a cancer screen? What was the result?"

“The result was ‘probably not,’ but the other option is ‘almost certainly not’ so we’d like to do more tests to make sure.”

(If the patient presses for more information, you don’t need to pull out the textbook yet; a simple analogy to explain why a cancer screen needs more tests might be by analogy to a rock screen, which sometimes catches clumps of dirt that need to be prodded a bit more to determine that they’re not actually stone.)

The important bit is to present it as routine and not yet a cause for concern, to avoid causing excessive alarm.

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