5 Lessons

1. Early detection saves lives but not always.
Catching cancer early can reduce death. But sometimes it just means knowing you have cancer without changing the outcome. That’s the paradox: “earlier” isn’t always “better.”

2. Every test has tradeoffs.
False positives mean worry, biopsies, and procedures you didn’t need. False negatives mean missed cancers. No test is perfect, and pretending otherwise sets people up for disappointment.

3. Context is everything.
Age, family history, and lifestyle risks shape whether a test helps more than it hurts. Screening isn’t one-size-fits-all. It’s tailoring, not blanket rules, that makes it smart.

4. Numbers can mislead.
“50% fewer deaths!” sounds dramatic until you check the baseline. If 2 in 1,000 people die without screening and 1 in 1,000 die with it, that’s a 50% drop, but only one life saved. Understanding absolute vs. relative numbers matters.

5. The system is as important as the science.
Even the best test is useless if people can’t afford it, get to the clinic, or follow up. Access, logistics, and trust are where lives are often saved or lost.

What’s Next for Screening

1. New frontiers
From blood tests that claim to detect dozens of cancers to AI that reads scans faster than doctors, new tools are arriving quickly. Some may change the game, while others may prove more hype than help. It will take time and strong evidence to sort out which innovations truly save lives.

2. More personalization
The future of screening looks more individualized. With genetics, lifestyle, and family history shaping decisions, concierge-style medicine may move from luxury to expectation, giving patients screening plans that actually fit them.

3. Shifting guidelines
Screening recommendations will keep changing as science improves. That does not mean the experts are confused. It means we are getting sharper about what works, who benefits most, and when screening stops being helpful.

4. A bigger role for patients
The next chapter is not just about tests, it is about conversations. New tools and more tailored recommendations mean patients will increasingly be asked to decide what matters most to them. Instead of a single default answer, screening will become a shared choice that reflects personal values as well as medical evidence.

5. Equity challenges
The promise of new tests only matters if everyone can access them. If innovation reaches only the wealthy or urban, gaps will widen. But if we design smarter systems that cover costs, reach rural clinics, and simplify follow-up, we could close some of the deepest divides in cancer outcomes.

Thanks for following along and learning with us. Our next series will dive into the world of wellness and longevity to determine what is actually evidence-based vs. what may just be the newest fad - starting with wearable technology.

Balancing Overdiagnosis, Risk, and Patient Expectations

Q: Do you get pushback from patients about screening decisions?

Dr. Arenberg:
Yes, absolutely. Some patients are very anxious and insist on being screened even when they don’t qualify. They’ll say things like, “My dad died of lung cancer—I need to know.” It’s tough, but part of our job is education and shared decision-making.

While we are very good at identifying risk brought on by tobacco exposure. We're terrible at understanding the risks that drive cancer in people who never use tobacco. There's data mostly from China, Asia, Taiwan, Hong Kong that air pollution tracks pretty closely with that. Not a surprise. Anything you burn and put in your lungs is bad. I tell people the only thing they should put in their lungs is clean air, and air pollution is no different from tobacco. It's just that tobacco happens to be addicting.

The other part of my career is trying to advocate for people who smoke and to do as much as we can to help them make and succeed at quit attempts. I try to help them not get discouraged. The average person who used to smoke made 6 or 7 or 8 quit attempts before they were fully successful. So I always tell people, don't feel ashamed. You know you're in good company if you're trying to quit, and you haven't been able to. I'm just there to support them and try to destigmatize the issue. I roll the tobacco cessation thing up into the screening, because I think they're very, very tightly related.

But the issue of people who've never smoked, or who are still worried about cancer. That's, I think, a very, very difficult conversation to have. I do not have all the answers, but I will sit down and spend an hour with people and say, “You know, here's why we do this. Here are the risks.”

The Inhalation Dilemma: Vaping, Marijuana, and Lung Health

Q: How does vaping factor into lung cancer screening?

Dr. Arenberg:
We don’t currently screen people who vape unless they also have a cigarette smoking history, because we just don’t have the long-term data yet.

That said, vaping is clearly addictive and harmful in its own right. I see it as a public health issue, similar to how we approached needle exchanges for drug users. It’s not a perfect solution, but if vaping helps someone quit cigarettes, that’s a step in the right direction. I tell my patients who smoke that their enemy is combustible tobacco. It's not nicotine.

Most of my patients are adults who've been smoking 30, 40, 50 years, and smoking cessation is the hardest thing they'll ever do. So anything we can do to help them get away from combustible tobacco, I consider a victory. I think there's some nuance there that's important to talk about.

Still, we have a long way to go, especially with teenagers vaping at high rates. The flavors, packaging, and marketing make these products very appealing to young people, and that’s a huge concern. You should never put anything in your lungs on purpose that isn’t air.

Q: What about marijuana? Does that affect screening recommendations?

Dr. Arenberg:
There’s some evidence of health benefits from THC for certain patients, but chronic marijuana use (especially smoking several times a week) may have health consequences we don’t fully understand yet.

We don't screen based on marijuana use alone, but it’s definitely something we pay attention to, especially when it overlaps with tobacco use. I think there's a lot of reason to be concerned about combustible marijuana as a public health problem that's going to cause long-term effects that we'll start to see in 10 or 15 years.

Bridging Gaps and Looking Ahead

Q: What are some of the barriers to equitable lung cancer screening?

Dr. Arenberg:
Access is a major barrier—transportation, time off work, insurance, health literacy. We’ve seen tobacco use is higher in communities with fewer resources, and unfortunately those are often the same communities that lack access to quality healthcare.

Outreach is key. I’ve gone to libraries and community events where we might talk to just seven or eight people, but those people go home and tell others. That kind of peer-to-peer trust is powerful, especially in underserved communities.

In England, they've started lung health checks. They'll park a semi truck in a parking lot. People will come through and get smoking cessation, advice, a pulmonary function test, and a CT scan. And that's their lung health check. Sometimes it's a branding issue instead of calling it lung cancer screening, because lung cancer has this stigma, unfortunately, that follows it around. That's our fault. We did that. We need to undo that. But until we undo that, the branding behind lung cancer screening might include referring to it as a lung health check.

So I think we need to be creative. I think this is again where a government can have an impact on the health of the population by assuring that barriers to access like transportation and time off from work to go to an appointment are addressed.

Q: Where do you see lung cancer screening in the next 10–30 years?

Dr. Arenberg:
I think we’ll see more personalized screening tools. We’re already exploring biomarkers and blood tests that could predict cancer risk or detect cancer earlier, maybe even before a CT scan could.

I also hope to see us target high-risk populations more effectively, especially those with social or economic barriers. Prevention is the ultimate goal—if we can stop people from smoking in the first place, we won’t need to screen as much.

Q: What’s one big takeaway you want readers to know?

Dr. Arenberg:
Don’t be discouraged if the screening process feels complicated. If you qualify, it can save your life, but it’s not one-size-fits-all. Talk to your doctor, ask questions, and make a decision together that makes sense for your health. If you smoke, ask for help to quit smoking. Don’t get discouraged when you don’t succeed the first, second, third, or tenth time. Don’t quit quitting.

Thank you to Dr. Arenberg for sharing his insight into the complexities and challenges of lung cancer screening. His perspective highlights just how important it is to tailor screening recommendations to each individual’s health and risk factors. As he explained, it’s not just about meeting age or smoking criteria—it’s about ensuring the right care reaches the right people at the right time. Increasing awareness, improving uptake, and addressing patient concerns are all key steps toward more effective screening. We appreciate Dr. Arenberg’s time and thoughtful discussion on this critical issue.

How Lung Cancer Screening Evolved

Q: What inspired your interest in lung cancer screening and prevention?

My interest in this area really began with personal experiences. I had family members affected by cancer, and I remember the helpless feeling when someone says, "We think you may have cancer, and your appointment is in three weeks." The idea of people waiting around for that answer is very uncomfortable for me. So I've spent my career effectively trying to shrink the amount of time that people have to deal with that uncertainty.

Lung cancer especially stood out to me—it’s traditionally had very poor statistics, though we’re seeing some reasons for optimism now. Whether it's through better treatment, management of side effects, or prevention efforts like tobacco cessation, there are a lot of promising avenues.

Q: How have you seen lung cancer screening evolve throughout your career?

So back in 1994-1995 during my fellowship, lung cancer screening was not a thing. It was actually specifically recommended that we do not do lung cancer screening. And a lot of it was because of very good data that had come out of studies done in the 1970s that effectively showed that lung cancer screening with chest X-rays didn't work. This makes sense because there's really no such thing as a routine chest X-ray.

But in the early 2000s, a group out of New York started doing lung cancer screening CT scans. The first time I read this paper, I thought, well, this is ridiculous. And then, when you read the fine print, you realize it's not ridiculous. It's pretty interesting. They demonstrated some metrics of uncontrolled studies that suggested maybe this was a different way to go.

Then the National Lung Screening trial picked up on this, and it became the largest ever cancer screening trial completed that showed an actual mortality benefit for lung cancer screening in particular. (Editor’s Note: mortality benefit refers to a decreased risk of dying from a specific disease, in this case, lung cancer)

I think you have to emphasize the mortality benefit. Because I think if you ask the average person on the street, “Why do we screen for cancer?” The answer you're going to get is going to sound something like “early detection, detect more cancers, longer survival.” And I think a lot of people have a hard time understanding that not one of those is an indication that that screening test actually works. The only metric through which a screening test can be measured is if it reduces your chances of dying from that cancer.

Long story short, lung cancer screening is up there with mammography, colonoscopy, and perhaps pap smears as the best screening test that we have for cancer.

Q: Who is eligible for lung cancer screening?

Lung cancer screening isn't as straightforward as other cancer screenings. With colon cancer, you turn 50 and your primary care provider tells you it's time for a colonoscopy. Ten years later, the calendar event comes up, and it’s time for your colonoscopy again. Same with breast cancer screening. It's basically, do you have the organ? And are you of a certain age? If yes, then go get the screening.

With lung cancer, eligibility is not only based on age, but also smoking history and overall health. The current USPSTF criteria for who should be screened includes people between the ages of 50 and 80 with more than 20 pack years of tobacco use. The guidelines also state that people should stop (or should not start) screening once they have developed conditions likely to limit their life expectancy. We tend to forget, even for other cancers, that people who have advanced comorbid disease that is likely to limit their life expectancy are not going to benefit from cancer screening at all. The problem with lung cancer screening is that the thing that makes you eligible for lung cancer screening is also what gives you other significant comorbid disease.

Cardiovascular disease is still the 800-pound gorilla in public health. It still kills more people than other diseases, but the curves will cross at some point, and things like COPD and lung cancer will overtake cardiovascular disease as we get better at preventing it, diagnosing it, and treating it. So the value of cancer screening will go up over time. But recognizing who's really eligible and who has the greatest potential to benefit from lung cancer screening is frankly more complicated than other cancer screening modalities.

Why Lung Screening Eligibility is Complicated

Q: Are there other challenges in implementing lung cancer screening?

Another major challenge is uptake: outside the VA system, only about 20% of eligible people get screened. Changing behaviors is hard. There’s also the challenge of finding lung nodules that end up being nothing, which can cause unnecessary anxiety or procedures. They've already googled lung nodule, and they've found lung cancer. Patients have an incidentally discovered nodule and they're scared, really, really scared. So the first thing I tell everybody is, statistically speaking, this is probably not lung cancer, and we judge the probability of lung cancer based on age, tobacco history, the appearance of the nodule, and the size of the nodule. We roll all that up into kind of an estimate, and based on that guide our next steps.

Again, as we try to get that number up above 20% of the eligible population. We also have to recognize that not everybody who's of that age with tobacco use history will benefit from screening. There are people who have significant comorbid disease with less than 5 or 10 years of life expectancy. They probably don't benefit from cancer screening of any sort, lung cancer screening in particular.

The goal is the right healthcare at the right time for the right people.

Q: What are you looking for when deciding whether a patient should be screened?

We assess general health, smoking history, and life expectancy. The goal is to identify people who would truly benefit from screening and could handle potential treatment, like surgery or radiation, if cancer is found.

For example, if a patient is too sick to undergo surgery, we don’t have solid evidence that screening will reduce mortality for them. That’s why we focus on patients who are healthy enough for intervention.

I have a lot of friends who are radiation oncologists, and they would scream at me and say, “But we can treat lung cancer with radiation.” And I say, that's absolutely true. It's a great treatment for people who can't have surgery on their lungs. But we don't have evidence that people who are ineligible for surgery have a mortality benefit from lung cancer screening. They were specifically excluded from all the clinical trials, and I think it's going to be hard to get that evidence. So I tend to stick to what the data allow me to say, which is, if you're otherwise healthy and can tolerate lung surgery, then lung cancer screening is for you if you've used tobacco in your life.

Also, screening isn't a one-time test. It's an annual commitment, much like always putting on your seatbelt. It's most effective when done consistently over time. If you're going to do cancer screening, you have to follow the prescribed intervals. Otherwise, the test doesn't achieve the aims for which you are doing it.

Thank you to Dr. Arenberg for sharing his expertise on lung cancer screening with The Medical. As he emphasizes, lung cancer screening isn’t just about checking boxes, it’s also about finding the right care for the right people at the right time. With its unique risks and complexities, lung cancer screening demands thoughtful conversations between patients and providers. But when done right, it’s one of the most powerful tools we have to save lives. In the second part of our conversation, Dr. Arenberg will tackle the barriers keeping patients from getting screened and where the future of early detection might be headed.

The Role of Patients in Screening Decisions

How should patients be involved in deciding if screening is right for them?
“We toss around the term ‘shared decision making,’ but the truth is, we do a terrible job of it. Some people say it’s impossible; I disagree. It may not always meet the gold standard, but we can approximate it—and it’s better than nothing.

That said, we don’t need shared decision making for every cancer. Cervical screening is a good example—it’s so clearly beneficial that I don’t do a big decision-making spiel.

But in cases where the evidence is more equivocal, like mammograms at age 40 for low-risk women or PSA testing for prostate cancer, we absolutely should.

I often present it as a values scenario: Some people want to know as early as possible, even if it means false positives and biopsies. Others say, ‘If it ain’t broke, don’t fix it.’

In prostate cancer, especially, the downstream path is long: elevated PSA → biopsy → maybe cancer → maybe treatment or surveillance. That’s a big cascade, and patients need to know what they’re getting into.

And sure, some still say, ‘Whatever you think, Doc,’ but at least they’re doing so from an informed place.”

What’s Stopping More People from Getting Screened?

“The barriers are huge. I was just reading a survey in an American Indian population— 4% were up to date on colorectal screening. Four percent. That shocked even me.

The biggest issues are access and equity. Too many people are uninsured or underinsured. We have a primary care shortage. We lack public health infrastructure.

So we can make great guidelines, but it’s academic if people can’t access care, don’t have a doctor, or don’t even know they should be screened.

Personally, I believe in a universal, baseline insurance plan that covers essentials like screenings, vaccines, primary care, and hospitalizations. If you want more, you can pay for more—but everyone should have access to the basics.”

Where Cancer Screening Is Going — From Guidelines to Genomics

What’s Changed Most Since You Started Practicing?
“Pap smears and HPV testing together are probably the biggest win. Cervical cancer used to be the most common cancer in women—now it’s relatively rare in the U.S., though still common in resource-poor countries.

If I can stretch beyond screening, the HPV vaccine is huge. It’s the first vaccine to prevent cancer. If everyone got vaccinated, we might not even need cervical screening anymore, or at least we wouldn’t need to screen as intensively.

Colorectal screening is another area with big change. When I started, we were using rigid sigmoidoscopes—basically medieval tools. Now we have colonoscopy, stool-based testing, and even CT colonography. And mortality has declined accordingly.”

What Excites You About the Next 10 Years of Screening? And in the Next 30 Years?

“In the next 10 years? Probably more refinement in personalized risk assessment—age, sex, family history, maybe even genotyping. That’ll help us screen the people who need it and skip those who don’t, or at least reduce screening intensity.

Longer term—30 years? I think blood and urine biomarkers will be the big disruptors. Things like multi-cancer early detection (MCED) tests. They’re not ready for prime time yet, but they could transform screening entirely.

But again, we’ll need to prove they reduce mortality—not just that they detect cancer.”

The One Thing to Remember

So, What’s the One Thing You Want the Average Reader to Know?

“Simple: Get screened.

Yes, living a healthy lifestyle is the most important thing. But screening—at the right time and for the right person—is a meaningful way to reduce your risk of dying from cancer, which is still the second leading cause of death in the U.S.

Talk to your doctor about which screenings apply to you.

We have a long way to go as a country in terms of access and education. But for the individual: screening saves lives.”

We’re deeply grateful to Dr. Andrew Wolf for sharing his time and perspective. As both a practicing internist and Chair of the American Cancer Society’s cancer screening guideline group, he brings a rare mix of clinical wisdom, national leadership, and humility to the evolving science of early detection.

Learn more about the ACS guidelines at cancer.org or speak with your healthcare provider about which screenings are right for you.

Now, as Chair of the American Cancer Society’s screening guideline group, Dr. Wolf has a front-row seat to how screening decisions are made — and why they’re harder than they seem. In this conversation, he explains what patients need to know, where guidelines come from, and why shared decision-making is both essential and often overlooked.

What Cancer Screening Is-And Isn’t

How did you get involved in cancer screening?
“My evolution in the world of cancer screening was pretty organic… I started my first job out of residency in a community hospital in an underserved area in Boston… at the same time the PSA blood test was just coming into widespread use. It was the first blood test widely recognized as a screen for cancer—a kind of panacea.

I was an early adopter. And then a patient of mine, who had early prostate cancer found through PSA screening, had surgery and came back completely incontinent. He said, ‘I wish you'd never found the cancer.’ That really got me thinking—did I do the right thing? I told myself maybe I saved his life. Maybe. Maybe not. But I do know the downstream effect was a major hit to his quality of life.

That led me to start thinking about informed decision-making in cancer screening. When I moved to UVA, I ran a small randomized trial funded by a grant from the American Cancer Society—just giving patients better information. Unsurprisingly, once men understood the pros and cons of PSA screening, some chose not to be screened. That got attention and led me deeper into this work.

Over time I became involved with the ACS guidelines, starting with prostate, and eventually chairing the merged guideline development group. That was a 30+ year evolution.”

How do cancer screening guidelines get made?
“We don’t initiate research ourselves. ACS has a separate arm that does that. What we do is assemble a panel—largely primary care generalists, plus a few cancer epidemiologists and statisticians.

For each type of cancer, we also assemble a panel of specialists—urologists, oncologists, radiologists, etc.—depending on the site.

We begin by defining key questions: What are the benefits of screening? What are the harms? Then, our internal evidence team does a systematic review and rates the quality of the evidence. Often, we also bring in modelers to help us figure out things that randomized trials don’t tell us—like what age to start and stop screening, or what the optimal interval is.

Then the full group deliberates. Do the benefits outweigh the harms? Is this test feasible? Are there groups that need different recommendations?

After drafting a guideline, we send it out for feedback from stakeholders and other organizations. We include patient representatives as well. Ultimately, the general guideline group decides.”

Balancing Risk: Why More Isn’t Always Better

How do you weigh the risk of overdiagnosis versus missing a treatable cancer?
“Overdiagnosis is a huge concern, but a hard one to explain — especially to the average patient. The idea that there are cancers not worth finding… that don’t grow or harm you? That’s not what people think of when they hear ‘cancer.’

The reality is that overdiagnosis varies a lot. It depends on the cancer, the screening method, the natural history. For example, we used to think lung cancer was never overdiagnosed, but we now believe there are some very slow-growing ones. In contrast, prostate and breast cancers have significant overdiagnosis concerns.

What we do is individualize. In prostate cancer, for example, we’ve reframed our goal: it’s not just to detect cancer—it’s to reduce death and suffering from metastatic disease. We don’t want to find every case, just the clinically important ones.

New techniques help. MRI-guided biopsies help us find high-grade cancers and avoid overdiagnosing the low-grade stuff. And ‘active surveillance’—where we monitor instead of treating right away—helps reduce unnecessary treatment.

Also, the longer you follow people in trials, the more some ‘overdiagnosed’ cases turn out to be important after all. In the European prostate trials, after 20+ years of follow-up, the estimated overdiagnosis rate dropped a lot.”

Tell us about a time you had a deeper conversation with a patient about fear of cancer vs. fear of the test.
“I had a patient in his 70s who had PSA anxiety. He’d been tested by a urologist, and the result came back elevated—not super high, but enough to worry him.

I said, look—you’re older, and we have no good evidence that screening at your age helps. I recommended we stop testing. But I also said, if you’re really anxious, it’s reasonable to get a biopsy and be done with it.

His anxiety won out. We got an MRI—it showed a suspicious lesion. The biopsy came back Gleason 7, so he got radiation treatment (Gleason score of 7 represents an intermediate grade cancer which may grow in a slow or moderately aggressive manner).

I think he felt like we saved his life. But he developed diarrhea and rectal bleeding, and soon after, he was diagnosed with primary progressive aphasia. He’s now in later stages of dementia.

So maybe we helped him. Maybe not. But I think we caused more harm than good.

That’s why I often say to patients, ‘Congrats, you made it to 70 or 75 with no signs of cancer. Let’s stop screening. You’re more likely to die peacefully in your sleep than from cancer.’ And that’s usually true.”

A huge thank you to Dr. Andrew Wolf for sharing his insight on the history, complexity, and nuance behind cancer screening guidelines. His reflections reveal how much thought and care go into balancing evidence, patient experience, and public health priorities. In our next post, Dr. Wolf explores the role patients play in making screening decisions, the systemic barriers that still limit access, and the emerging technologies that could reshape the future of early detection.

You can learn more about the ACS guidelines at cancer.org or speak with your healthcare provider about which screenings are right for you.

This week’s piece is authored by Dr. Hart, a guest contributor to The Medical. Drawing on her expertise and perspective, Dr. Hart breaks down the key factors that shape how and why we screen for cancer.

1. Cancer Screening Guidelines Aren’t One-Size-Fits-All

Cancer screening recommendations can be confusing, largely because major health organizations don’t always agree. For instance, the U.S. Preventive Services Task Force (USPSTF) recommends stopping prostate cancer screening at age 70 and mammograms at age 75. In contrast, the National Comprehensive Cancer Network (NCCN) suggests that anyone with at least five years of expected life should be considered for screening, especially as many older adults are living longer, healthier lives. This reminds us that these guidelines are not end-all be-all obligations, but rather evidence-based suggestions we should use to make individualized decisions.

2. Screening Only Makes Sense if You’d Act on the Results

Shared decision-making is essential. If a patient is unwilling or unable to undergo treatment if cancer is detected, then screening may not be beneficial. This is particularly important in patients with multiple other health issues where cancer may not be the most immediate threat. In such cases, the risks, anxieties, and burdens of screening may outweigh the benefits—especially if life expectancy is already significantly limited by competing conditions.

3. Newer Screening Tools Are Promising, But Not Perfect Either

Patients often hope for a simple blood test to detect cancer, and while tests like PSA (for prostate cancer) are widely used, they can lead to unnecessary worry, testing, and costs without always identifying true disease. The future of screening lies in developing less invasive, cost-effective tools with minimal radiation exposure and good accuracy. For now, it is important to follow the guidelines in a way that makes sense for you.

We’d like to thank Dr. Hart for sharing her insights and expertise with our readers. Her thoughtful perspective helps bring clarity to a topic that can often feel complex and overwhelming.

1. Mortality impact: We screen when a cancer is common enough and deadly enough that earlier detection significantly reduces the risk of death. Cancer is the second leading cause of death behind cardiovascular diseases in the United States. Cancers with the highest mortality are shown below which include lung, colorectal, pancreas, breast and prostate. If you were to screen for less common cancers, then it would not be as efficient or effective. The research and development that goes into these screenings is intensive too. We want to get the most bang for our buck. So by screening for the most common cancers, it ensures that the benefits outweigh the costs and risks.

   

2. Detectable early phase: The cancer must have a long enough window where it can be found before symptoms appear, and early detection actually changes the outcome. That outcome may be either mortality or morbidity. Yes, improving lifespan is important but so is quality of life. Screening can be worthwhile for quality of life such as preventing debilitating symptoms or the need for harsh treatments. You may have noticed that while we screen for many of the cancers mentioned above, we don’t screen for all of them. Take pancreatic cancer for example. It has a high mortality rate but we do not screen for it because it displays rapid growth and it is difficult to treat. This brings us to our next point.

3. Effective early treatment: Screening is only worthwhile if catching it earlier allows for treatment that meaningfully improves survival or quality of life. Just as in the example above with pancreatic cancer, treatments must be able to make a meaningful impact.

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4. Quality of screening test: The test must be accurate (high sensitivity/specificity), relatively safe, and acceptable to patients/providers. Otherwise false positives, false negatives, and harms from unnecessary procedures outweigh the benefits.

5. Balancing benefit vs harm: Screening can lead to overdiagnosis and overtreatment, so the net gain in healthy years lived must justify the screening effort. Over the past decades, research has informed guidelines from the United States Preventive Services Task Force (USPSTF), an independent panel of national experts in prevention and evidence-based medicine. The USPSTF develops recommendations on clinical preventive services, including screening, assigning letter grades (A, B, C, D, or I) based on the strength of evidence and the balance of benefits and harms. These recommendations apply to otherwise healthy individuals without signs or symptoms of the condition being evaluated.

Letter grades guide clinicians on which screenings are appropriate and determine insurance coverage, with A and B grades requiring coverage without cost sharing. Linked here is the USPSTF grade definitions sourced from their official guidelines.

An example of a letter A grade is the recommendation that we screen adults aged 50 - 75 for colorectal cancer. On the other hand, adults aged 76 - 85 years of age receive a letter grade C. This illustrates how various factors, like age in this example, can affect the balance between benefits and harms.

Another example is prostate cancer screening, which has a grade C. This means individuals should discuss with their healthcare provider whether the potential benefits outweigh the harms and whether screening aligns with their personal values and preferences.

If you remember from our last post in this series, we took a look at the epidemiological signatures of different cancer types. Those signatures discussed previously, generally align well with the given recommendations.

In general, screening is a difficult thing to do. It is not easy to impart a benefit to an otherwise healthy asymptomatic person without causing harm. So first and foremost, a screening test needs to provide benefits which outweigh the harm. Here are some great infographics for mammography and prostate cancer screening.

It is important that if you have questions or concerns, to speak with your provider. Here are some examples.

• How do I feel about undergoing testing, potential follow-up procedures, or possible anxiety from results?

• How might early detection change my chances of survival or quality of life for the specific cancer being screened?

• What is my personal risk for this cancer based on age, family history, genetics, and lifestyle?

• Do I have any medical conditions that make screening more or less important?

In our next few editions of this series, we will share conversations we’ve had with experts in the field where we discuss their thoughts on how you can best make cancer screening work for you.

In a barn there is a bird, turtle, and rabbit. Around the barn is a fence meant to keep the animals inside. The animals represent the variety of ways that cancer can progress and the implications that screening has on each. The turtles represent slow growing cancers that have a very low probability, if at all, of causing symptoms and escaping past the fence. In fact some of these cancers may even regress or become stagnant, never to cause symptoms in one's life. The rabbits are faster, and if caught early, there is a better chance of treating the cancer. Some of the rabbits escape but many are kept inside the fencing. Lastly, the birds represent cancer that is fast growing and malignant, that even with screening, we are unable to impose much benefit. The birds subsequently escape outside of the fencing. The goal of screening is to catch the rabbits because that is where we can provide that greatest benefit with the least harm.

So what is overdiagnosis bias? Overdiagnosis bias is a bias that occurs when a screening test identifies a disease that was never going to cause symptoms or result in death. This can occur when you catch slow growing cancers or “turtles”. Overdiagnosis may lead to unnecessary treatment, increased anxiety, and financial strain.

Overdiagnosis is best visualized through an epidemiological lens. If you zoom out and look at the incidence of cancer diagnoses and death from cancer over time, it is evident just how much overdiagnosis there is. In Epidemiologic Signatures in Cancer, Welch et al. explore patterns of incidence and mortality for various cancers. I will discuss the basics of their paper below. Keep in mind that not all cancer screenings are created equally.

Above is the epidemiologic signature for overdiagnosis. The example above is of melanoma. You can see an increase in the incidence by nearly five fold over a 40 year span meanwhile the mortality rate has barely budged. What does this mean? It means we are finding and diagnosing more melanoma yet it is making little difference in the amount of people who die from melanoma. Technically we do not screen for melanoma. The American Cancer Society does not provide specific guidelines for early skin cancer detection, but many physicians and experts advise individuals to perform regular self-examinations of their skin.

And here we can see that the incidence and mortality rates decrease over time. In cervical cancer, the decline is generally attributed to effective screening, which allows for the detection and treatment of precancerous changes before they progress. Additionally, success can be attributed to the success of vaccination against HPV strains, which are known to cause a significant portion of cervical cancers.

This last figure shows a mixed picture of both overdiagnosis and possible success. The blue column in the figure shows when screening was started for both breast and prostate cancer. For breast cancer, incidence rose sharply with the introduction of widespread mammography and has since stabilized at a higher level, likely due to overdiagnosis rather than a true increase in disease, as suggested by the stable rates of metastatic cases. Mortality has declined since the 1990s, likely due to improved treatments more than screening. Prostate cancer incidence also surged with PSA screening but later declined, indicating its volatility to changes in screening practices rather than actual disease trends. While screening appears to advance the timing of diagnosis for metastatic cases, it may not ultimately change the course of the disease. The observed mortality decline is likely due to a mix of better treatment and earlier detection.

As you can see there are many ways in which the survival from cancer may be altered whether it be through early diagnosis, treatment, or risk modification. The cancers we screen for are not created equally. Some are excellent, others fall short, and some lie somewhere in the middle.

Thank you for reading this week’s edition in The Medical’s Cancer Screening series!

Lead time bias occurs when a test seems to improve survival rates simply by detecting a disease early, without actually changing the time of death. To understand lead time bias, we must first start with defining survival. Survival is the time from diagnosis to death.

We can increase the time of survival in two ways. First, we may prolong time until death—via treatment. Second, we can diagnose early—via screening.

Next, we must define lead time. Lead time refers to a disease being detected earlier compared to if the individual waited until symptoms appeared. This is because screening finds disease before symptoms start, so it makes the diagnosis happen earlier than it would without screening. Therefore, the diagnosis occurs earlier than it would without screening, simply because the disease is detected at an asymptomatic stage.

A screening test will invariably introduce a lead time and when you introduce a lead time, you introduce lead time bias. This bias occurs because the disease is diagnosed earlier, which artificially inflates the survival time. Thus, screening for cancer always extends survival time by virtue of introducing lead time.

However, remember that we can also increase survival time by prolonging time until death through treatment. Through treatment, we can modify the severity of disease, manage complications, and even cure disease entirely. Effective treatments can result in a true increase in survival by changing the underlying course of the disease.

So, this begs the question, do patients live longer overall or do we just find cancer earlier? Or perhaps a combination of both? To answer this question we use randomized control trials. By creating balanced groups, we can evaluate whether a screening is able to effectively make one group live longer than the other and not just increase their survival time.

Absolute risk (AR) is the probability of an event occurring in a population. Here is an example. If in group A (wears seatbelt), 5 out of 100 people get injured in an accident, the absolute risk is 5%. If in group B (not wearing seatbelt), 20 out of 100 people get injured in an accident, the absolute risk is 20%. We can elaborate further by using absolute risk reduction (ARR), which is the difference in risk between two groups. In this case, the absolute risk reduction would be 15%.

• 20% absolute risk - 5% absolute risk = 15% absolute risk reduction

Relative risk (RR) is the probability of an event occurring in one population compared to another population. People who wear seatbelts (group A) have 25% of the risk of getting injured in an accident compared to those who don’t wear seatbelts (group B).

• 5% absolute risk ÷ 20% absolute risk = 0.25 relative risk

Similarly, we can use relative risk reduction (RRR). So we could say that your risk of getting injured in an accident is reduced by 75% if you wear a seatbelt compared to no seatbelt.

• 100% - 25% = 75% relative risk reduction

Everything above is briefly summarized below. . .

• AR tells you each group's risk

• ARR tells you “You’re 15% less likely overall to get injured if you wear your seatbelt.”

• RR tells you “If you wear your seatbelt, you have 25% of the original risk of getting injured.”

• RRR tells you “The risk of getting injured is reduced by 75% if you wear a seatbelt compared to no seatbelt.”

We will use a couple more examples to drive this point home.

Example #2:

Your absolute risk of dying from disease X is 40% without treatment (group A)

Your absolute risk of dying from disease X is 20% with treatment (group B)

ARR: You are 20% less likely to die from disease X if you receive treatment

RR: If you receive treatment, you have 50% of the original risk of dying from disease X

RRR: The risk of dying from disease X is reduced by 50% of the original risk.

Example #3:

Your absolute risk of dying from disease X is 4% without treatment (group A)

Your absolute risk of dying from disease X is 2% with treatment (group B)

ARR: You are 2% less likely to die from disease X if you receive treatment

RR: If you receive treatment you have 50% the original risk of dying from disease X

RRR: The risk of dying from disease X is reduced by 50% of the original risk.

This same information is represented visually in the following table:

So why does all this math matter? Because it can shift how we interpret risk and influence the importance we assign to it.

Looking at the example above, you may have noticed that RRR stayed the same (50% for both examples) but the ARR changed from 20% to 2% for example #2 and #3, respectively. This underpins the importance of distinguishing the type of risk someone is referring to. Oftentimes, RRR can sound more impressive than it actually is. Saying that a treatment cuts your risk of death in half compared to no treatment sounds like a huge benefit. But what you also want to know is the ARR. If your risk of death is reduced from 4% down to 2% with treatment, it may not sound as extraordinary. An ARR of 2% (4% - 2% = 2%) means that 98 out of 100 will see no difference and not live any longer had they not received treatment. If a treatment is expensive or has bad side effects would you still consider it? Would you undergo a treatment if it helps 2 out of 100 people? This is a much different way of thinking rather than “treatment cuts the risk in half compared with no treatment”.

More often, RRR tends to be used in headlines, media, and even doctors. If we are being honest, big numbers are exciting and small numbers are boring. If a large number is used to quantify risk, then it may be referring to RRR. In that case, it would be helpful to find out what the ARR is. Neither ARR nor RRR is better than the other. They are best when used together to provide a full honest picture. Good decisions come from clear, complete information.

Prior to doing a test, a person has a baseline probability of having a disease. This is called a pre-test probability which refers to your estimated probability that a patient has a disease before the test is done. Pre-test probability depends on a multitude of factors such as…

• Disease prevalence - ​​this is how common a disease is

• Patient-specific factors - things such as age, sex, and lifestyle greatly impact the baseline probability that someone has a disease

• Clinical presentation - signs and symptoms that a patient presents with

• Temporal context - outbreaks, travel history, exposures, and regional patterns are important

As an example, if a patient presents with fever and a cough during the winter season, you are more likely to think of the flu than if this patient presents in the middle of the summer. Another example is that females are much more likely to have breast cancer as they have significantly more breast tissue compared to males. These are all factors that may increase or decrease your suspicion of someone having a disease prior to performing a diagnostic test.

Likelihood ratios help us refine pre-test probability by showing how much a test result should shift our level of suspicion for a disease. A diagnostic test result can be positive or negative, but neither one guarantees whether a person actually has or does not have the disease.

For example, let’s say you get a positive test result. You may ask yourself, how likely is it that this person truly has the disease given the positive test result? A positive result alone doesn’t give you a definitive answer as it could be a true positive, but it could also be a false positive. This is where likelihood ratios come in.

A positive likelihood ratio (+LR) tells us how much more likely a positive test result is in someone with the disease compared to someone without it. A negative likelihood ratio (−LR) does the opposite. It tells us how much more likely a negative result is in someone without the disease than in someone with it.

Likelihood ratios can be evaluated using commonly accepted thresholds that indicate their diagnostic usefulness. A positive likelihood ratio greater than 10 strongly increases the likelihood of disease. A negative likelihood ratio of 0.1 or smaller strongly decreases the likelihood of disease.

Chan, G.M., Su, M.K. Biostatistics and Epidemiology for the Toxicologist: Likelihood Ratios. J. Med. Toxicol. 20, 411–415 (2024).

For completeness’ sake, below are the formulas to calculate both the positive and negative likelihood ratios. You can now see why this topic comes after our discussion on sensitivity and specificity, as both are essential components in these calculations.

LR(+)=Sensitivity1 - Specificity LR(-)=1 - SensitivitySpecificity

Once you know your pre-test probability, you can apply the concept of likelihood ratios to determine your post-test probability. Post-test probability is the probability that a person actually has (or does not have) a disease after the diagnostic test results come back. Below is a simple breakdown on the application of likelihood ratios.

1. Start with a pre-test probability. This is your initial estimation about how likely the disease is before testing (based on symptoms, risk factors, prevalence, etc.)

2. You perform a test and get a result (positive or negative)

3. Use the likelihood ratio from the test result to update your pre-test probability

4. The updated number is the post-test probability. That is, how likely the disease is given the test result

It can be easy to get caught in the weeds with this and that is not the point of this series. The key takeaway is that likelihood ratios help adjust our initial suspicion of disease in a way that can meaningfully guide clinical decisions. Be on the lookout for next week’s post, where we’ll apply likelihood ratios to explore whether blood-based colorectal cancer screening is a promising new tool for early detection.

When discussing cancer screening, there are some key concepts to know that will make understanding the complexity of cancer screening easier. We will start with the classic four by four table (AKA confusion matrix). Our goal is to make this simple to understand.

• True Positive: A diagnostic test correctly identifies a person with a disease (this is good)

• False Positive: A diagnostic test wrongfully identifies a person with a disease when the disease is not actually present (this is bad)

• True Negative: A diagnostic test correctly identifies a person without a disease (this is good)

• False Negative: A diagnostic test wrongfully identifies a person without a disease when the disease is actually present (this is bad)

Using the four terms we have defined above, we can move on to discuss sensitivity and specificity. We will use a simple fishing analogy that will make this easier to understand. A fishing net will represent our screening test, and the goldfish will represent the cancer we are trying to find. But first, let's define sensitivity and specificity.

Sensitivity: How good a test is at finding people who have the disease

• How good the net is at catching all the goldfish (cancer)

Specificity: How good a test is at finding people who do not have the disease

• How good the net is at catching all the blue fish (not cancer)

The perfect screening test will have a high sensitivity and a high specificity. Unfortunately, cancer screening is not perfect, and there are tradeoffs. A higher sensitivity means you're finding more true cancer cases. However, this often comes at the cost of lower specificity, meaning more false positives (people told they might have cancer when they don’t). On the other hand, increasing specificity will lead to fewer false positives (false alarms) but would decrease sensitivity, leading to false negatives (missed cancers). Real life is messy, and it is not easy to create a perfect screening test.

So why does sensitivity and specificity matter? It matters because if you have a high sensitivity, then more cancers are caught early and may be treated, hopefully saving lives. On the flip side, a test with high specificity helps avoid diagnosing people who are actually healthy which saves time, money, and worry.

The use of mammograms for breast cancer screening is a great example of this tug of war between sensitivity and specificity. Mammograms have a higher sensitivity and lower specificity. Many women are identified who may have breast cancer, with the caveat that a fair number are also wrongfully told they might have breast cancer.

So, how do we try to catch more real cancers while avoiding unnecessary worries in healthy people? One strategy is to focus screening efforts on people who are at higher risk for specific cancers. By narrowing the population we screen, we can aim to design programs that are more accurate, more useful, and less likely to cause harm.

This is why most screening guidelines are tailored to specific groups based on age, sex, family history, and other risk factors. In these populations, the balance between benefit and harm is more likely to favor screening. Understanding how tests work and who they’re meant for is key to making informed decisions.

Every screening tool involves tradeoffs, and there’s no one-size-fits-all solution. By carefully considering who we screen, how we screen, and what we do with the results, we can use these tools more thoughtfully, aiming to help without causing unnecessary harm.

As always, we’d love to hear your thoughts. Feel free to share your thoughts or questions in the comments below.

For millennia, medicine has concentrated its efforts on treating medical ailments and disease acutely. With the passing of time, the content and knowledge of medicine has grown tremendously. We now have a better understanding why and how diseases present the way they do. With this increase in understanding, efforts were made to take a proactive approach to medicine which we call preventive medicine.

Although discussions around preventative medicine were occurring in the mid-1800s, it was not until the early 1900s that we started to see the implementation of such tests. In 1923, the American Medical Association endorsed the practice of early disease detection in healthy persons through periodic health exams. This marked a formal shift in the medical model from treating illness after it occurred to attempting to intercept it in its earliest stages.

This concept was soon applied to the field of oncology. As our understanding of cancer grew, we sought to be proactive in finding cancer early so that it would be easier to treat. The commonly understood view of cancer was that it followed a linear path and that it progressed through different stages eventually leading to symptoms. It was thought that we may be able to intervene at the earlier stages if we can find it early. And so the first cancer screening to be implemented was invented by Andromache Papanicolaou in 1928 for the early detection of cervical cancer. However, it wasn't until 1941 that the Papanicolaou smear (now commonly known as a pap smear) was proven to be effective and its use became widespread.

At the time, approval and implementation of screening tests were less stringent than they are today. The early adoption of screening tools was often driven by biological plausibility and clinical intuition rather than rigorous empirical evidence.

The year 1948 marks a pivotal point in medical history when our approach to evidence changed. It was the first time a randomized controlled trial had been completed. Soon, screening tests were being subjected to the same rigorous standards of evidence-based medicine.

Prior to randomized controlled trials, advancements in medicine were made through intuitive thinking and deductive reasoning. This is the same thinking that led to the development of cancer screening- the idea that detecting cancer early increases the chances of a cure. However, the emergence of evidence-based medicine revealed that not all screening practices were benign or beneficial.

Over the subsequent decades we gleaned insightful information into benefits and harms that screening may subject us to. Born out of these trials was a newfound scrutiny and a more critical view of screening that was not so simple as previously thought.

This growing body of evidence led to the emergence of critical appraisal frameworks such as those used by the U.S. Preventive Services Task Force (USPSTF). These groups began issuing screening recommendations based on a careful balance of benefits, harms, and population-level data. Screening started to be seen as something that should be more personalized, depending on factors like age, gender, medical history, and individual risk.

Over time, our approach to cancer screening has changed from something based mostly on intuition to a process that’s guided by evidence and careful evaluation. While the original idea that finding cancer early would make it easier to treat still holds true in many cases, we now understand that screening isn’t always straightforward. It comes with both benefits and potential harms, and it’s not a one-size-fits-all solution. Today, screening is more personalized, taking into account a person’s age, risk factors, and medical history. As we move forward, the focus continues to shift not just toward detecting cancer early, but toward preventing it altogether. This ongoing evolution shows how medicine continues to grow, always building on what we've learned to better care for patients.

As we continue in our cancer screening series, we’ll next look ahead at how evolving research, new technologies, and better risk prediction may help us refine cancer screening to minimize harm while maximizing benefit.

Medicine has changed a lot over time. In the past, doctors mostly treated people after they got sick. But in the mid-1800s, there was a shift toward preventing illness before it started. Today, many doctors focus on keeping people healthy, not just treating diseases. For example, family doctors don’t just help when you’re sick—they also give checkups, vaccines, and advice on staying healthy. While our healthcare system still focuses a lot on treating illness, prevention is now a bigger part of medicine than ever before.

Preventive medicine helps stop diseases before they get worse. There are three main types:

• Primary prevention stops diseases before they start.

• Secondary prevention finds diseases early, before symptoms appear.

• Tertiary prevention helps people manage serious illnesses and reduce their impact.

Preventive care has made a big difference in public health. Vaccines are a great example of primary prevention. Measles has been eliminated from the United States since 2000 and smallpox eradicated worldwide since 1980. These are a testament to the success of vaccines and primary prevention.

Cancer screening, a type of secondary prevention, is the focus of this series. Unlike other medical tests, cancer screenings check healthy people who have no symptoms. This is why we must be sure the benefits of screening outweigh any risks.

The idea behind cancer screening is simple: find cancer early, when treatment may work best. The goal is to prevent serious illness and death. Since cancer is the second leading cause of death worldwide, it makes sense to look for ways to catch it early. As we delve into the science and ethics of cancer screening, our goal is not to provide a one size fits all answer but rather a nuanced overview so that more thoughtful discussions can take place between healthcare providers and patients.