health screening tests

Understanding Cancer Screening Tests: Absolute vs Relative Risk Reduction

The benefit of cancer screening tests like pap smears, colonoscopy, mammography and others are reported in two ways. The most common way is the relative risk reduction. This is a ratio of the risk in the screened group divided by the risk in the non-screened group. Relative risk does not take into account the baseline risk in the whole population. The other way of reporting benefit of a screening test is called absolute risk reduction. Absolute risk reduction is the risk in the non screened group minus the risk in the screened group. Relative risk reduction always looks a lot bigger than absolute risk reduction because it does not take into account the baseline risk. Absolute risk reduction is what you really want to know. Absolute risk reduction lets you know how much your risk is reduced by taking the screening test. It is always a lot lower than the relative risk reduction. Absolute risk reduction of the most common cancer screening tests is very low, usually 1% or less.

Here are some examples:

Mammography: Relative breast cancer death risk reduction 30%; Absolute cancer death risk reduction 1%
Colonoscopy: Relative colon cancer death risk reduction 50%; Absolute death risk reduction 0.15%
Pap Smear: Relative cervical cancer death risk reduction 80%; Absolute cervical cancer risk reduction .08%
PSA (test for prostate cancer): Relative risk reduction 64%; Absolute risk reduction .09%

Another number that can be helpful is called Number Needed to Screen (NNS). NNS is the number of people who need to be screened to prevent 1 death from the disease. NNS is just 1 divided by the absolute death risk reduction for the screening test. Here are the NNS’s for the examples above.

Mammography: NNS 1/.01= 100 (this is mammograms every 2 years from age 50-75 so the the 100 patients means about 1100 mammograms).
Colonoscopy: NNS 1/.15=667
Pap Smear: NNS 1/.08=1,440
PSA: NNS 1/.09 =1,111

Sensitivity and Specificity

Any test, including cancer screening tests have a certain sensitivity and specificity.

Sensitivity

The sensitivity of a test is the probability that the test will detect the disease if it is present. In other words it measures how likely it is to get a false negative test. The higher the sensitivity, the less likely the test will be negative if the person has the disease being tested for. It is expressed as a percentage.

Specificity

The specificity of a test is the probability that a person with a positive test will have the disease. In other words it measures how likely it is to get a false positive test. The higher the specificity, the more likely a person with a positive test will have the disease. It is also expressed as a percentage

An ideal test has both a high sensitivity and specificity. Lets look at the sensitivity and specificity of our cancer screening tests.

Mammography: sensitivity 72%; specificity 98%
Colonoscopy: sensitivity 85%; specificity 90%
Pap Smear with HPV testing: sensitivity 95%; specificity 97%
PSA: Sensitivity 30%; Specificity 91%

Bayes Formula

All of these cancer screening tests have high specificity but somewhat less sensitivity except for Pap smears with HPV testing, which have high sensitivity and high specificity. So why are the absolute death reductions so low? Part of it has to do with something called Bayes Formula. It turns out that the chance of a false positive has to do not just with the specificity, but also the frequency of the disease in the population being screened. If the frequency of the disease in the population being screened is low, then even with a test that has high specificity, the chance of a positive test being a false positive is higher than than the specificity would suggest. The frequency of all of the above cancers is low in any 1 year in the population so that means that false positive cancer screening screening tests are common. Below are population frequencies for each cancer per year.

Breast cancer: annual prevalence in women 0.13%. Chance of a positive mammogram being a true positive: 28%. This means that a positive mammogram has 72% chance of being a false positive. On the other hand, a negative mammogram has an 8.7% chance of being a false negative, that is of missing a breast cancer
Colorectal cancer: annual prevalence in population .03%. Chance of a positive colonoscopy being a true positive: 2.5%. That means that a colonoscopy that finds something only has a 2.5% chance of being cancer. On the other hand, a negative colonoscopy has only a .005% chance of being a false negative. That means a negative colonoscopy has only a tiny chance of missing a cancer.
Cervical Cancer: annual prevalence in population 0.0077%. Chance of a positive pap smear being cancer: 0.24%. That means that 99.86% of positive pap smears with HPV testing will not be cervical cancer. On the other hand the chance that a negative pap smear with HPV testing will be a false negative is .00041%. Obviously a negative pap smear with HPV has an infinitesimally small chance of missing a cervical cancer. Although the chance of finding a cervical cancer is very low, the pap smear with HPV also finds precancerous changes in the cervix. Treatment of these precancerous cells prevents cervical cancer from developing. That is a big reason why the prevalence of cervical cancer is so low.
Prostate Cancer: annual prevalence in men .66%. Chance of a positive PSA (>4) being a true positive 2.18%. That means a PSA of >4.0 has a 98% chance that no prostate cancer is present. On the other hand a PSA of <4.0 has a 5.1% chance of missing a prostate cancer.

The somewhat lower sensitivity of mammography, colonoscopy and especially PSA means that false negatives are fairly common, for these tests.

The combination of false positives, false negatives and low prevalence of these cancers in the population all contribute to the small absolute death risk reduction for all four of these cancer screening tests. For patients at substantially higher risk, such as strong family history of breast or colon cancer, the screening tests perform much better, because the high risk population has a much greater disease prevalence than the general population.

Over Diagnosis

Another problem with cancer screening tests is over diagnosis. Over diagnosis means that a positive test finds a cancer, but the cancer grows so slowly or spontaneously disappears so that it never would have caused any symptoms in the person. Over diagnosis then leads to unnecessary treatment. So let’s look at the over diagnosis rate for our four cancer screening tests.

Mammography: Over diagnosis rate for women 40 and over is 12%. This means the 12% of women diagnosed with breast cancer by mammography will be treated for cancer unnecessarily.
Colonoscopy: The over diagnosis problem with colonoscopy results from the removal of polyps. All visible polyps are removed during colonoscopy. The polyps that have some chance of turning into cancer are called adenomatous polyps. Only 8% of these turn into invasive colon cancer over 10 years. That suggests that 92% of the adenomatous polyps removed at colonoscopy would never turn into cancer. Removal of all adenomatous polyps does prevent some colon cancers. It is not possible to know at the time of removal which polyps are going to progress. The cost of prevention of some colorectal cancers is substantial over diagnosis.
Pap Smear with HPV: Overdiagnosis of precancerous cervical lesions is high. We now know that cervical cancer is caused almost exclusively by the HPV virus. On the other hand, women often clear an HPV infection on their own without treatment. This is particularly the case with young women, which is why pap smears and HPV testing are not recommended before age 21. Precancerous cervical lesions are graded CIN1-CIN3, CIN3 being the most severe. Overdiagnosis rates are higher for the lower grade lesions, which most often clear on their own. The figures for over diagnosis over women’s lifetime were 70.6% for CIN1+, 63.2% for CIN2+, and 50.0% CIN3+.
PSA test for prostate cancer: Low grade prostate cancer is common as men age. Many of these cancers would never cause symptoms during the lifetime of the men. Current estimates are that 60% of prostate cancers detected by PSA would never cause symptoms or death from prostate cancer. Treatment of prostate cancer often results in permanent urinary incontinence and/or sexual dysfunction. This very large over diagnosis and therefore unnecessary treatment is why PSA testing is so controversial. There are certain populations of men who are at high risk of aggresive prostate cancer and these men are probably the only ones who should have routine PSA testing. Here is a link to a risk calculator for prostate cancer: PCPT Risk Calculator.

Bottom Line

Despite the high specificity of cancer screening tests, Bayes Formula shows that false positive tests will be more frequent than true positive tests. For mammograms, colonoscopy and PSA the somewhat low sensitivity means that there will be some false negative tests. In other words, they will miss a few cancers. Pap smear with HPV has the lowest chance of missing a cancer. Over diagnosis is a problem with all cancer screening tests, resulting in unnecessary treatment. This is particularly a problem for breast cancer and especially prostate cancer. The low absolute death risk reduction values and the over diagnosis problems for these tests do not mean you should not be screened, especially if you are in a higher risk population due to family history or other causes of higher cancer risk. All of these screening tests save lives, just not as many as the relative risk values suggest. The vast majority of people will not benefit from these tests and some will be harmed by unnecessary treatment, but a small but substantial number will have their lives saved.

Longevity – Health Span vs Life Span

Longevity is the newest health buzzword. There are an increasing number of so-called longevity experts. They say, just read my book and follow my instructions and you can live past 100 years. Some of these “experts” focus on health span. They say follow my instructions and you will stay healthy and die suddenly at an advanced age. As of 4/21/2024 there are 34 books on longevity listed on Amazon.

In this post I will do my best to distinguish the hype from the science with regard to living a long and healthy life.

Hype

Calorie restricted diets – Some people have extrapolated mouse and rat experiments that show that animals fed restricted calorie diets live a lot longer than animals fed a normal diet. There is not one shred of evidence that this works with humans, and is more likely to lead to diseases of malnourishment.
Nutrtional supplements – Recommendations range from vitamins, to protein powder, to collagen powder, to herbal preparations, to encapsulated fruits and vegetables. There is absolutely no evidence that any of these things or any other supplements including multivitamins work to extend your life. Anecdotal reports of feeling better on these supplements are almost certainly a placebo effect
Anti-aging medicines – reservetrol, metformin, rapamycin have all been shown to prolong life in some experimental animals. In humans Metformin and reservetrol decrease the ability to exercise and rapamycin suppresses the immune system. There is no evidence whatever that these compounds increase life or health span in humans.
Extensive lab tests – Other than lipid (cholesterol) tests, there is no evidence that otherwise healthy non-obese people benefit from any blood tests. More about screening tests later.
Imaging tests – One of the most popular longevity “experts” ,Dr. Peter Attia, recommends full body MRI scans for his patients. Imaging tests in people who have no symptoms are much more likely to lead to over diagnosis and unnecessary treatment than to find things that really need to be treated,
Very intense exercise regimens – The only thing very intense exercise regimens accomplish that moderate exercise regimens do not is that the intense regimens are more likely to cause injury.

Science

Genetics

Up until into the 80’s, lifestyle is the major contributor to healthy aging. There are some people, however who remain healthy well into their 90’s and a few to past 100. Genetics is the main contributor to these “super centenarians.” There is not a single or even a few aging genes. Super aging is caused by hundreds of genetic variants called SNP’s (single nucleotide polymorphisms). We cannot alter our genes (yet), so there are no lifestyle changes you can make in order to live to 100 if you don’t have the rare combination of all these genetic variants.

That is not to say that lifestyle is not important to healthy aging. In the US, the average person’s last birthday in good health is age 65! Lifestyle changes will almost certainly help you do better than that.

Exercise

Regular exercise decreases your risk of chronic disease and therefore increases your chance of living healthier longer. To accomplish the maximum health benefit the CDC recommends 150 minutes of moderate exercise per week. Brisk walking or cycling at a moderate pace on level ground would qualify. If you choose high intensity exercise like jogging or running or high intensity cycling, you only need to do 75 minutes a week according to the CDC. The CDC also recommends activity to strengthen your muscles two days a week. For a population of adults doing this exercise regimen the risk of death is decreased by 17%. This regimen decreases the risk of heart disease, diabetes, certain cancers and decreases the risk of hospitalization or death from infectious diseases like COVID, flu and pneumonia. This regimen also increases bone and muscle strength and thus decreases the risk of falls and fractures. This exercise regimen also helps maintain a healthy weight.

Any amount of walking or activity decreases risk somewhat. The CDC recommended regimen decreases risk the most.

Nutrition

Eat mostly unprocessed foods and avoid ultra-processed foods. The best way to identify ultra-processed foods is to look at the ingredients label. If there are more than four ingredients, and/or if there are some you don’t recognize, then put that food back on the shelf. It is best to keep nutrition advice simple. The most concise recommendation I know comes from author Michael Pollan. “Eat food (food is anything your grandmother would have recognized as food), not too much, mostly plants.” I can’t do much better than that. Most of the evidence about the beneficial effects of good nutrition come from studies of the Mediterranean style diet. The Mediterranean diet adheres to Michal Pollan’s advice. It has lots of fruits, vegetables, fish, olive oil and very little meat. Adherence to this type of diet showed a 46% increase in living healthfully until 70 or greater.

Social Connectedness

The CDC defines social connectedness as the degree to which people have and perceive a desired number, quality, and diversity of relationships that create a sense of belonging, and being cared for, valued, and supported. An analysis of multiple studies showed that high social connectedness as defined above decreases the risk of premature death by 50%! High social connectedness also decreases the risk of heart disease, stroke and dementia.

Social Determinants of Health

The main reason that the US average health span is 65 years is the tremendous inequity of resources in the US. People who live in substandard housing (or no housing at all) do not have the opportunity or resources to do all of the things above that tend to extend life. That is why life expectancy at birth is related to zip code more than any other factor. My feeling is that we should expend our resources working on improving health equity, which will increase both life and health span for everyone rather than focusing on helping wealthy people live to 100.

Screening Tests

There are a few screening tests recommended by the US Preventive Care Task Force for healthy people. These tests are meant to find disease, especially cancer early so it can be more successfully treated and thus prolong healthy life. The absolute risk reduction of death for these tests is small, most around 1%, but that ends up saving a lot of people when you apply it to the whole US population. The recommended screening tests are listed below.

Mammograms for women beginning at age 50. Recommended every two years. Absolute risk reduction about 1%.
Pap Smears beginning at age 21 every 3 years through age 29 and then every 5 years from age 30 to 65. The absolute death risk reduction is .0009%, which means your would need to do pap smears on 11140 women to prevent one death from cervical cancer.
Colorectal cancer screening. There are three different tests: colonoscopy, the most invasive (recommended every 10 years), Cologuard (a stool sent to a lab in a box recommended every 3 years) and fecal immunochemical test (done on a stool sample and either tested at home or sent to lab recommended every year). All three tests reduce deaths from colon cancer with an absolute risk reduction of around 0.6%. Only colonoscopy can prevent some cancers by removing precancerous polyps.

Vaccines

There is no question that vaccines save lives by preventing some serious life threatening diseases, or making them less severe. Vaccines are especially important for infants and children, who are most at risk from the infectious diseases prevented by vaccines. Childhood vaccines prevent diptheria, whooping cough, tetanus, measles, mumps, rubella, polio, rotavirus (which causes severe diarrhea and dehydration in infants), hemophilus influenza (which caused joint infections and meningitis), hepatitis b, RSV (which causes severe respiratory illness), pneumonia caused by strep (the most common kind of bacterial pnuemonia), COVID (also for adults), meningitis, chicken pox, and HPV (the virus that causes cervical cancer in women).

Adults can get any of these vaccines, but also a vaccine to prevent shingles.

Bottom Line

Living in good health to past 100 depends on genetics, not lifestyle. Many things recommended by so called longevity experts do nothing to prolong life and may increase risk. There are a number of lifestyle changes including exercise, good nutrition, social connectedness, certain screening tests and vaccines that increase you chances of remaining healthy well into your eighties. The main cause of early death in the US is poverty, homelessness and systemic racism. Addressing these inequities is a lot more important than helping wealthy people try to live to 100.

Too Much Medical Care – Just as Bad for You as Too Little

Medical care in the US is the most expensive in the world, but almost all our health outcomes are worse than other industrialized countries. We talk a lot about US populations that don’t have enough access to medical care, but this post is about people who get more medical care and procedures than they need. It turns out that too much medical care not only adds to costs, but is actually as bad for you as not getting enough medical care. I’m going to write about both diagnostic and surgical procedures that are unnecessary at best, and dangerous at worst.

Unnecessary Diagnostic Tests

Routine lab work at your annual preventive care visit

It is common for doctors to order “routine” lab work at preventive care visits. This often includes a complete blood count (CBC), a comprehensive metabolic panel (CMP), a lipid panel and a hemoglobin A1C (a long term blood sugar test).

Healthy people who are not overweight and have no symptoms don’t need any of these, except perhaps the lipid panel to screen for high cholesterol but not even that every year. If you are overweight and sedentary, then it makes sense to screen for diabetes or pre-diabetes with an annual hemoglobin A1C. If you have high blood pressure then it makes sense to do a basic metabolic panel, which includes a measure of kidney function once a year. Other lab work should be based on symptoms and risk factors.

One reason that doing unnecessary lab work is dangerous as well as costly is that the more tests you do on someone, the greater the statistical chance that at least one of them will be abnormal. That can lead to a cascade of further tests and even dangerous procedures.

Imaging for low back pain

There is no reason to do x-rays. CT scans or MRI scans for acute low back pain unless it lasts for more than 6 weeks. Imaging should be done sooner if “red flag” symptoms are present such as:

Fever or chills
Recent illness or surgery
Recent severe back injury
History of cancer
Unexplained weight loss
Night pain or pain at rest
Urinary or fecal Incontinence
Saddle anesthesia (loss of feeling in the buttocks and inner thighs)
Weak, numb, or painful leg muscles

Abnormalities on imaging, especially CT and MRI are often present in people who have no back pain. Imaging without red flags, could lead to unnecessary surgery or back injections.

CT or MRI scan for headache with no findings on neurologic physical exam

Headaches are common and the vast majority do not have a serious cause. Headaches without any other symptoms or history of head injury do not need any imaging. Headache in people who have a history of migraine headaches also do not need imaging. There are certain “red flag” symptoms that do require an immediate CT or MRI scan. These include:

Abnormal neurological examination (e.g. papilledema, altered mental status).
Signs of systemic illness (e.g., fever, stiff neck, rash).
Worst headache ever.
Progression in frequency and severity of headaches.
New headache in patients older than 50 years.
Sudden onset of headache – “thunderclap headache.”
New-onset headache in an immunocompromised or cancer patient.
Headache after head trauma.
Headache worsening with Valsalva (straining like you do to have a bowel movement).

DEXA scan for osteoporosis in low risk women before age 65 and in low risk men before age 70

The risk of fractures due to osteoporosis is extremely low in women under 65 and men under 70 who have none of the high risk factors outlined below. DEXA scans in people in this low risk population are not only unnecessary but also result in unnecessary radiation exposure. Radiation exposure is cumulative and can increase the risk of cancer.

Risk factors for osteoporosis include: a family history of osteoporosis, previous fractures, dementia, poor nutrition, cigarette smoking, alcoholism, low weight and body mass index, estrogen deficiency, early menopause (i.e., before age 45) or prolonged lack of menstrual periods in premenopausal women, long-term low calorie intake, history of falls, and inadequate physical activity.

Ultrasound of carotid arteries (carotid dopplers) in people who have no symptoms

People who have no symptoms are unlikely to benefit from carotid stents or surgery even if they have partial obstruction of the carotid arteries. They are much more likely to be harmed by surgery including risk of stroke, heart attack, or even death.

Carotid dopplers are only indicated for people who have symptoms suggestive of a stroke or mini stroke (TIA)

Routine PSA screening for prostate cancer in men

Although a few men’s lives will be saved by routine PSA testing, many, many more will have surgery for slow growing prostate cancer that would never affect their health, resulting in urinary incontinence and sexual dysfunction for a good portion of those.

PSA screening for prostate cancer should always involve shared decision making with the patient. Some people who have a strong family history of prostate cancer or other risk factors may opt for screening. It should never be routine.

Prostate cancer screening should not be done at all in men over 70. The chance of finding anything other than low grade prostate cancer that does not need treatment in men over 70 is very low.

Annual EKG’s (or any other heart screening test) in low risk people without symptoms

Heart screening tests, including resting EKG and exercise stress testing in people in a low risk population have a much higher false positive rate than true positives. This can result in unnecessary invasive procedures including cardiac catheterization and unnecessary heart surgery.

People with multiple risk factors might benefit from screening tests. Here is a link to a heart disease risk calculator: CV Risk Calculator. You will need to know your LDL and HDL levels to use this calculator. If your 10 year risk is over 10%, you might benefit from one of the heart disease screening tests.

Pap smears under age 21 and over age 65

A pap smear is a screening test for cervical cancer, which is caused by chronic infection with the HPV (wart) virus. Women under 21 who are infected with HPV most often clear it without treatment. It therefore makes no sense to screen women under 21 for cervical cancer. Women over 65 whose last pap smear or HPV test was normal have almost zero risk of contracting HPV, so no longer need pap smears.

Annual pap smears are no longer needed for anyone. Pap smears are recommended every 3 years for women age 21-29 and every 5 years from age 30-65 as long as an HPV test is done also.

Unnecessary Procedures

Stents for stable angina

Stents in the coronary arteries can be life saving for heart attack or unstable angina (heart pain that is getting progressively worse). Many people, however have stable coronary disease. They get pain with a predictable amount of exercise that goes away when they rest. It stays the same and does not get worse with time. People with this kind of stable heart disease do just fine when treated with medicines and lifestyle changes. They do not need stents. In fact, stents do not decrease all cause mortality (death) 4 years later compared to treatment with medicines. Some studies suggest that up to half of coronary stent insertions are unnecessary. Stent insertion is an invasive procedure that can have complications including death. You definitely don’t want to have one if it isn’t likely to extend your life significantly.

Hysterectomy (removal of the uterus) for benign disease

Most “elective” hysterectomies are done because of fibroid (benign) tumors, excessive vaginal bleeding, or endometriosis. All of these conditions have alternative less invasive effective treatments. Fibroids that are causing symptoms can be removed without a hysterectomy. Persistent vaginal bleeding can be treated with hormones or with removal of the lining of the uterus without doing a hysterectomy. Endometriosis can usually be treated effectively with hormones. Hysterectomy should be done only for cancer or when alternative treatments for benign disease have been tried and have not been effective.

Knee arthroscopy for arthritis

Osteoarthritis of the knee is one of the most common chronic healthcare conditions. It involves gradual deterioration of the joint surfaces including tears of the menisci. Knee arthroscopy involves using a tiny camera to look inside the knee through a small incision. Another small incision is made to insert small surgical tools. When orthopedists recommend this procedure to patients, they often say that they are going to “clean out” the knee. This means removing fragments of torn cartilage and pieces of meniscus.

People get temporary relief if any from this procedure. It is considered unnecessary surgery. It exposes one to the risks of general anesthesia and possible infection from the procedure.

Vertebroplasty for osteoporotic compression fractures

Compression fractures of the spinal vertebrae are relatively common in women (or men) with osteoporosis. Many times these are not painful and are found incidentally on x-rays. Sometimes they are painful, especially when they first happen. Vertebroplasty involves injecting cement into the fracture site to stabilize it and reduce pain. Most of the time short term pain medicines and temporary spinal braces provide adequate pain relief. There have been no well conducted double blind studies of vertebroplasty, so it is not known how much of the pain relief from this procedure is simply a placebo effect. It may help in very selected patients, but should only be done for persistent pain when conservative measures have failed.

Spinal fusion for back pain

Chronic back pain is a common condition. It can result from arthritis of the spine or can still be present even with normal x-rays. Spinal fusion surgery connects two or more spinal vertebrae together with small screws. Bone chips from the hip bone are used at the site of surgery as a bone graft, which eventually fuses the vertebrae together.

Spinal surgery of any kind, but especially spinal fusion is never appropriate for people with chronic back pain who have normal back x-rays. Osteoarthritis of the lower back, which does show up on x-rays, is best treated conservatively with physical therapy, non-narcotic pain medicines and walking as much as tolerated.

Spinal fusion is only indicated when there is severe instability of the spine that is causing pressure on the spinal cord. This is not a common finding, so spinal fusion is only rarely indicated.

One problem with spinal fusion is that there is increased mobility of the spinal facet joints above the level of the fusion, which can cause recurrent pain. This can lead to another fusion, which is caused by the first one.

Bottom Line

Unnecessary diagnostic tests and lab work increase the probability of unnecessary surgical procedures. You should ask your doctor or nurse practitioner the reason for any diagnostic tests or lab work that they order. If the answer is “routine” then you should consider declining the test.

If any elective surgery (that means not emergency surgery) is recommended you should ask if there is a more conservative option. You may also always request a second opinion. For any of the low value procedures outlined above you should be very wary of having that procedure unless you have one of the red flag indicators.

Cancer Screening: Always a No Brainer? Maybe Not

First, let me be clear about the definition of cancer screening. Screening for cancer is done for people who feel well and have no symptoms that suggest they might have cancer.The goal is to detect cancer early, before you have symptoms, so that hopefully it is easier to treat and cure.

If you have symptoms of cancer, then tests such as mammograms or colonoscopy are for diagnosis of a disease, not screening. If you are a woman who has a breast lump or abnormal uterine bleeding, or a man with a lump in the testicle, or anyone who has rectal bleeding or difficulty swallowing food, or feeling full after just a little food, you need to see your doctor right away and be tested for cancer. Here is a link to a web page from UCSF that has a more comprehensive look at symptoms of cancer for which you should see your doctor: 17 Cancer Symptoms You Shouldn’t Ignore.

In this post I am going to write about the available screening tests for cancer. For many cancers there are no good screening tests. A good screening test has to meet several criteria. The first is that it detects a kind of cancer that responds better to treatment when detected early. There are other criteria for a good screening test as well. Here is a link to a web page from the American Medical Society Journal of Ethics that talks about all the criteria for a good screening test: What Makes a Screening Exam “Good”?

I will discuss how well each of them work and how well they fit the criteria for a good screening test. I will also write about the risks of getting cancer screening tests (there are some substantial risks).

Cervical Cancer Screening (and Prevention)

Screening for cervical cancer is the poster child for an effective screening test. It is inexpensive, has no significant risk and detects both cervical cancer and pre-cancerous changes. It develops slowly, so it is an ideal cancer for screening. Early detection leads to much more effective treatment even before cancer develops. Since the 1940’s, when the pap smear was invented, death from cervical cancer has decreased by over 70%.

We have learned a lot about cervical cancer since the 1940’s. We now know that cervical cancer is caused by certain strains of the wart virus, otherwise known as HPV (human papilloma virus). The recommendation used to be that women should have a pap smear every year starting after beginning sexual intercourse. We now know that women under 21 most often clear HPV on their own, and there is no reason to do pap smears before age 21. If the pap smear is normal and the HPV test is negative, then for women 30-65 years of age, it is not necessary to do another one for five years. Women over 65 who have had two previous normal pap smears can stop cervical cancer screening.

Not only can the pap smear and HPV test detect cervical cancer early, but they can detect pre-cancerous changes that can be treated before cervical cancer develops. Even better, there is now a vaccine that prevents HPV and therefore cervical cancer altogether. It is called Gardisil, and should be given to adolescent girls and boys before the age they start having sexual intercourse.

Like other screening tests, most women will not benefit from cervical cancer screening. We would have to do pap smear and HPV screening on 1,140 women for ten years to prevent one death from cervical cancer. That means that 1,140 out of every 1,141 women will not benefit from cervical cancer screening,

Breast Cancer Screening

Mammograms are the primary and most studied screening test for breast cancer. Breast cancer is not as ideal for screening as cervical cancer, because some breast cancers develop very rapidly and can spread aggressively between mammography screenings. That means that some women die from breast cancer even if they get regular mammograms. Mammograms also have a high false positive rate, which can lead to more invasive unnecessary tests such as breast biopsies. The false positive rate for any kind of mammogram, including the newer 3D mammograms is 50% over 10 years!

Mammograms do save lives, but a lot fewer than people think. Here is a table from the US Preventive Services Task Force website that shows the benefits and harms of mammograms every two years for every 1000 women screened.

Table 3. Lifetime Benefits and Harms of Biennial Screening Mammography per 1000 Women Screened: Model Results Compared With No Screening*

Variable	Ages 40–74 y	Ages 50–74 y
Lives Saved	8 (5–10)	7 (4–9)
False-positive tests	1529 (1100–1976)	953 (830–1325)
Unnecessary breast biopsies	213 (153–276)	146 (121–205)
Overdiagnosed breast tumors	21 (12–38)	19 (11–34)

There are a few things to notice about this table. First, almost all the benefit in lives saved by screening is in the 50-74 age group but more false positives, unnecessary biopsies and overdiagnosis occurs in the group that starts mammography at age 40. The other thing to notice is the number of overdiagnosed breast cancers (overdiagnosed means that these tumors would never result in illness or death from the cancer) are much larger than the number of lives saved in each age category.

What this table says is that 125 women need to be screened with mammography to save one life from breast cancer. That is a great number! On the other hand, for every 47 women screened by mammography one woman gets overdiagnosed with breast cancer that would never harm her. That is a terrible number!

Given all this information, what should women do? Here are the US Preventive Services Task Force recommendations as of 2016. These recommendations are currently being updated, but the new recommendations are not available yet. The USPSTF recommends mammograms every other year, rather than every year. Every other year mammograms cut the risk of false positives in half, but result in the same number of lives saved.

Population	Recommendation	Grade
Women aged 50 to 74 years	The USPSTF recommends biennial screening mammography for women aged 50 to 74 years.	B
Women aged 40 to 49 years	The decision to start screening mammography in women prior to age 50 years should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. . For women who are at average risk for breast cancer, most of the benefit of mammography results from biennial screening during ages 50 to 74 years. Of all of the age groups, women aged 60 to 69 years are most likely to avoid breast cancer death through mammography screening. While screening mammography in women aged 40 to 49 years may reduce the risk for breast cancer death, the number of deaths averted is smaller than that in older women and the number of false-positive results and unnecessary biopsies is larger. The balance of benefits and harms is likely to improve as women move from their early to late 40s. . In addition to false-positive results and unnecessary biopsies, all women undergoing regular screening mammography are at risk for the diagnosis and treatment of noninvasive and invasive breast cancer that would otherwise not have become a threat to their health, or even apparent, during their lifetime (known as “overdiagnosis”). Beginning mammography screening at a younger age and screening more frequently may increase the risk for overdiagnosis and subsequent overtreatment. . Women with a parent, sibling, or child with breast cancer are at higher risk for breast cancer and thus may benefit more than average-risk women from beginning screening in their 40s.	C

Other groups recommend more intensive screening, but screening younger women and screening every year results in less than half a percent more lives saved and markedly increases the harms of screening including false positives and overdiagnosis. My feeling is that the USPTF recommendations make the most sense for women.

Prostate Cancer Screening

Screening for prostate cancer with the PSA (prostate specific antigen) is the most controversial of the cancer screening tests. Overdiagnosis with the PSA test is a huge problem. Autopsy studies done on men who died of other causes find that by age 80 more than half the autopsies show prostate cancer. Many, perhaps most prostate cancers grow so slowly that they will never cause any symptoms. More men die with prostate cancer than from prostate cancer. Overdiagnosis leads to radical prostatectomy for tumors that would never cause symptoms or death. Surgery for overdiagnosed tumors results in permanent urinary incontinence for half of men and sexual dysfunction for most of them. On the other hand, prostate cancer kills one out of every 41 men in the US. A good screening test for aggressive prostate cancer would be a wonderful thing. Unfortunately at this point we do not have such a test.

The US Preventive Services Task Force reviews all the available studies of screening tests and makes recommendations based on that evidence. Here is that review for the PSA test if 1000 men are screened with the PSA test annually for13 years,

	Number of Men Affected
Men invited to screening	1000
Men who received at least 1 positive PSA test result	240
Men who have undergone 1 or more transrectal prostate biopsies	220^b
Men hospitalized for a biopsy complication	2
Men diagnosed with prostate cancer	100
Men who initially received active treatment with radical prostatectomy or radiation therapy	65
Men who initially received active surveillance	30
Men who initially received active surveillance who went on to receive active treatment with radical prostatectomy or radiation therapy	15
Men with sexual dysfunction who received initial or deferred treatment	50
Men with urinary incontinence who received initial or deferred treatment	15
Men who avoided metastatic prostate cancer	3
Men who died of causes other than prostate cancer	200
Men who died of prostate cancer despite screening, diagnosis, and treatment	5
Men who avoided dying of prostate cancer	1.3

What this table shows is that of 1000 men screened for 13 years, there will be 100 men diagnosed with prostate cancer, but only 1 life saved as a result of screening and 2 other men who avoid metastatic prostate cancer. The cost of that life saved will be 97 men overdiagnosed with prostate cancer and 220 men that have a prostate biopsy. This is not a pleasant procedure and can sometimes result in complications such as infection, as indicated by the 2 men out of the 220 men that were biopsied that were hospitalized because of the biopsy. Five men out of the 1000 died from prostate cancer anyway despite screening, diagnosis and treatment,

African American men and men with a strong family history of aggressive prostate cancer are at substantially higher risk for aggressive prostate cancer. It is worth considering screening for this group. Men at average risk are more at risk for harm than help from prostate cancer screening, at least with the tests we have available now. The USPTF recommendation is that prostate cancer screening is an individual decision and should be discussed with your doctor.

Colorectal Cancer Screening

Colorectal cancer if caught early is almost 100% curable, but if it is not discovered until it invades the intestinal wall, the cure rate gets progressively worse.

Unlike breast cancer and prostate cancer, which have only one kind of screening test, there are a number of different screening tests for colon cancer. They each have advantages and disadvantages.

FOBT (Fecal Occult Blood Test)

This is the oldest test and also the one that has been studied the most. It is also the least expensive ($5-$10). People who do this test every year, and who have a colonoscopy if they have a positive test have reduced deaths from colorectal cancer by about 27%. That means that out of 1000 people who screen annually with FOBT, there will be 270 fewer deaths from colorectal cancer than people who do not do screening.

The biggest problem with this test is that it has a fairly low sensitivity of 50%, which means it will miss half of early colorectal cancers. It also has a fairly low specificity of 78%, which means that about 1/4 of the tests will be false positives.

FIT (Fecal Immunochemical Test)

This newer test is only positive for blood coming from the colon. That makes both the sensitivity and the specificity higher than FOBT. It is also fairly inexpensive (the home test costs about $25)

The sensitivity of the FIT test is about 75%, which means it will miss about 25% of early colorectal cancers. The specificity of the FIT test is about 90%, which means that the false positive rate is only 10%. Because the FIT test is relatively new, there are no randomized controlled trials of lives saved by FIT tests vs no screening. Estimates based on computer models suggest that annual FIT testing with colonoscopy for positive tests would reduce deaths from colorectal cancer by 74%! That means that of 1000 people who screen with the FIT test and get colonoscopy for positive tests, deaths from colorectal cancer will be reduced from 1782 deaths to 457 deaths.

There are several different kinds of FIT tests. Some require sending a stool sample to a lab, but the home test is just as good and is less expensive. The one that seems to work the best is from Pinnacle Biolabs. Here is a link to their website where you can order a test: Second Generation FIT® 1 Pack.

Cologuard

Cologuard is the only commercially available DNA test. It measures the specific DNA shed by cancer cells. It is actually a combination test and includes a FIT test as well. This increases the sensitivity, but decreases the specificity, which means that the Cologuard test has a higher false positive rate than the FIT test alone. It is also very expensive, about $600 per test. A stool sample has to be collected and sent to the lab. Computer modeling suggests that deaths from colon cancer for 1000 people would be reduced from 1782 deaths to 1143 deaths. Not nearly as good as the FIT test alone.

Colonoscopy

Although some groups consider colonoscopy to be a screening test, many organizations feel that colonoscopy should be used only when another screening test is positive. People who are at high risk of colon cancer should probably have colonoscopy as a screening test. Colonoscopy done every ten years, with follow-up exams every 3 to 5 years when polyps were found, would reduce deaths from 1782 deaths to 624 deaths.

Colonoscopy is the most sensitive and specific test, but also carries much more risk as a screening test. Serious complications (bleeding or perforation) occur in 44 people out of every 10,000. 3 people out of 100,000 die from colonoscopy. The average number of colonoscopies to result in one serious complication is 225. It is also very expensive (average cost $1,700). It may seem counterintuitive that FIT testing saves more lives, but that is because it is easy to do FIT testing every year and screening colonoscopies are done only every 10 years. One advantage of colonoscopy is that it reduces the chance of getting colon cancer by identifying and removing pre-cancerous polyps.

Lung Cancer Screening

For a long time we had no good screening test for lung cancer. Annual chest x-rays were shown to be worthless for lung cancer screening. Now there is a screening test for lung cancer. It is a low radiation dose CT scan. It should be done every year, but only for people aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.

False positives are a huge problem with lung cancer screening. Of people who get a positive result, 97% of those will be a false positive, meaning no cancer will be found on further testing. Further testing may include a needle biopsy of the lung, which can result in a collapsed lung.

The number needed to screen to prevent 1 lung cancer death is about 300. The number needed to harm (false positives or over diagnosis is 19. Although lung cancer screening with low dose CT does save lives, it comes at a substantial cost of false positives and overdiagnosis.

Common Cancers with No Good Screening Test

There are no good screening tests for ovarian cancer, uterine cancer, pancreatic cancer, esophageal cancer, leukemia, or Hodgkin’s disease (cancer of the lymph nodes. Many of these cancers are treatable once they are found, but they are found because of symptoms, not because of screening.

Galleri test

This is an update to this post, which I just published. Galleri is a new blood test that detects DNA shed by cancer cells. The company claims that it will detect 50 different types of cancer. Although this technology is promising, it is not yet ready for prime time. It is very good at detecting advanced cancer, but not very good at detecting stage 1 cancers when they are most treatable. There is also a high false positive rate of about 30%. Hopefully this technology will improve. If that happens, it will be a game changer with regard to cancer screening.

Bottom Line

If you are higher risk for any of the cancers for which we have screening tests, then getting screened is something you should do. If you are at average or low risk, screening tests are unlikely to help you and may harm you. Everyone should be alert for red flag symptoms that mean you might have cancer. The purpose of this post is not to discourage cancer screening, but to give you information that you should have when making a decision about whether and which cancer screening tests you choose.

More on Health Screening – Fecal Occult Blood Test (FOBT)

As noted in the previous post, 19 people out of 1000 will eventually die from colorectal cancer. In this post I will discuss another screening test for colorectal cancer, checking stools for tiny amounts of blood.

You do this test at home once a year. Your doctor will give you a kit to do the test. The kit contains three small disposable wooden sticks and 3 cards connected together. When you have a bowel movement, you open one of the cards, reach down into the toilet with one of the sticks and get a small amount of stool to smear on the special areas on the card, and then close the flap on the card. You do the same thing for two more bowel movements on two different days for the other two cards. The cards usually come with a special sealable pre-addressed envelope so that you can mail the cards back to your doctor’s office. Your doctor’s office staff opens the other side of the card and puts special developing solution on the card. If it turns blue, then there is some blood in the stool smear. If the test is positive, then a colonoscopy is recommended. Certain foods, such as horseradish and certain raw vegetable can cause a false positive test. Lots of meat or vitamin C can also cause false positives. These foods should be avoided the day before the three days of testing.

Unlike colonoscopy, there has been very extensive testing of the effectiveness of FOBT in reducing the risk of death from colon cancer. If you do this test every year, your risk of death from colorectal cancer is reduced anywhere from 16% to 27% in several large randomized trials. This means that there would be three to five less deaths per 1000 people. In other words the 19 per thousand death rate would be reduced to 14 to 16 deaths.

Once again, if you are at average risk your chance of winning this lottery, that is your chance of finding early treatable colon cancer is small, about .003 to .005.

What about the risks of the FOBT?

The false positive rate (the test says you have cancer or a polyp but you don’t) is high, about 45%. This means that of 100 people who have a positive FOBT test, 45 will turn out not to have cancer or a pre-malignant polyp.

The false negative rate (you have colon cancer but the test says you don’t) ranges from 21% to 45% depending on which study you look at. This means that of 100 people who have colon cancer, the test will be negative in 21-45 of them.

The over diagnosis rate is not applicable here, since any positive FOBT test will be followed by a colonoscopy.

Harm from the test itself is not a problem. This is a non-invasive test that is done at home and there are no physical harms from the test.

What is the bottom line?

Although this test has a relatively high false positive and false negative rate, it is the only test that has been proven to decrease the death rate from colon cancer in people at average risk, it is non-invasive, safe and it is very inexpensive. If you have a higher than average risk of dying from colon cancer, then colonoscopy is the better choice.

More on Health Screening Tests – Colonoscopy

As promised, the next few blog posts will discuss the risks and benefits of common health screening tests.

Colorectal cancer is the second most common cancer in both men and women in the U.S. Your lifetime risk of dying from colon cancer is 1.94%, which means that 19 people out of 1000 will eventually die from colorectal cancer.

The most commonly recommended screening test for colon cancer is colonoscopy. In this test a long flexible tube with a small camera on the end is passed from the anus all the way to the end of the colon (large intestine). For the test to work well, the colon has to be completely cleaned out of feces, so strong laxatives are given the night before the procedure to clean out the colon. Most people find this to be the most unpleasant part of the test! For the test itself, a sedative is given through a vein because the test would be very uncomfortable without it.

A small instrument can be passed through the tube to remove any polyps that are found. Polyps are small growths on the wall of the colon. Certain kinds of polyps, called adenomatous polyps, have about a 15% chance of eventually turning into cancer but only about fifteen people out of a hundred have this kind of polyp.

So if you have this test, how much does it reduce your chance of dying of colon cancer? Unfortunately, we have no idea! There has never been a good study of colonoscopy in the general population to answer that question. All we know is that, based on one not very good study, people who were at higher than average risk of colon cancer and who had adenomatous polyps had about half as many deaths over 16 years than would have been predicted for the general population.

There is a commonly used rating scale for quality of evidence that goes from A (very good) to D (very poor). This study would get a C at best.

All we can say at present is that for people at average risk for dying from colon cancer, colonoscopy reduces that risk somewhere between 0% (not at all) and probably a lot less than 50%.

What about the risks of getting a colonoscopy?

As we discussed in the previous post, risks for any health screening test include:

False positives (the test says you have the disease when you don’t)
False negatives (the test says you don’t have the disease when you do)
Over diagnosis (you have the disease to such a small degree that it will never harm you)
Physical harm from the test itself.

False positives: False positives are not a significant problem with colonoscopy.

False negatives: The false negative rate for colonoscopy is about 10%. This means that one out of every 10 people eventually diagnosed with colon cancer will have had a normal colonoscopy.

Over diagnosis: The smaller the adenomatous polyp is, the less likely that it will eventually turn into cancer. People with very small polyps are at low risk for dying of colon cancer, but are often encouraged to have colonoscopies every three to five years. This exposes them to the risks of colonoscopies that they don’t need. This is over diagnosis.

Physical Harm:

Risk of death: a small number of people die from having a colonoscopy. The death rate is about .03%, which means out of every 10,000 people who have a colonoscopy, 3 people will die from it.
Risk of perforation (poking a hole in the colon): The risk of perforation ranges from 0.1% to 0.3%, which means that one to three people out 1000 who have a colonoscopy will have a perforation. If this happens it often requires surgery to remove a part of the colon.
Hemorrhage (bleeding): the risk of bleeding after a colonoscopy is 0.1% to 0.6%. This means that one to six people out of 1000 who have colonoscopy will have bleeding that requires either repeat colonoscopy, surgery, or some other procedure to stop it.
Abdominal pain and bloating: although not life threatening, this can be very uncomfortable. The risk of bloating is 25% and the risk of abdominal pain can be as high as 11%. This means that of 1000 people who have a colonoscopy, 250 will have bloating and 110 will have abdominal pain after the colonoscopy.
Gas explosion: This is a very rare, but very dramatic complication. If there is methane gas in the colon from an incomplete cleaning of the colon and oxygen is introduced by putting air in to distend the colon, then use of cautery(an electric current) to remove a polyp can cause an explosion in the colon. There are only a few case reports of this, so we don”t know the exact risk, but it must be very small.

So what is the bottom line?

If you have a higher than average risk of colon cancer because of a family history of colon cancer or some other disease or condition that increases your risk, then it probably makes sense for you to have a colonoscopy. We have one not very good study that supports this.

If you are at average risk, however, your chance of preventing or finding early colon cancer is uncertain, but likely small and the chance of having a complication (and some of them are pretty serious) is probably at least as high or higher than your chance of benefiting.

How is health screening like playing the lottery and how is it different?

Lots of people like to buy lottery tickets. The chance of winning is exceedingly small, but the risk is also small, is known, and is experienced up front: a little bit of money. People who buy lottery tickets make the decision that the entertainment value of thinking about winning is worth the small cost. It is a pleasant experience for those who do it.

Having a health screening test is a little like playing the lottery, but there are some important differences. Winning this kind of lottery means that you find a disease or condition that might kill you early enough to treat it successfully. If you are at average risk for the condition being screened for, your chances of winning this lottery are also very small. The risks for this kind of lottery are also small, but unlike buying a lottery ticket, the risks are uncertain and are not necessarily experienced up front. Risks include having a false positive test (the test says you have the disease but you don’t), a false negative test (the test says you don’t have the disease but you do) or complications of the test itself that may cause physical harm. You may also be over diagnosed, which means that you have the disease, but it is so small or minor that it would never harm you. Over diagnosis means that you are likely to get treatment that you don’t need, which may indeed harm you.

Take breast cancer for example. If you are a caucasian woman without any high risk factors your lifetime risk of dying from breast cancer is 2.7% (If you click this link, look at table 1.20), which means that 27 caucasian women out of 1000 will eventually die from breast cancer. African American women have a somewhat higher risk. Mammograms every other year from age 50 changes that number to 25. That is a reduction in absolute risk of half a percent. For a single mammogram the absolute risk is reduced by only about five hundredths of a percent, which would change the 27 number to 26.95 Clearly, your chance of winning this lottery are very small.

The false positive rate for mammograms is 60 % which means that if 1000 women have mammograms, 600 of them will have abnormal mammograms that don’t turn out to be breast cancer. This is a high risk that can cause worry and psychological harm

The false negative rate for mammograms is 20%, which means that of 1000 women who have breast cancer, 200 of them will have normal mammograms. This is not a very accurate test!

The over diagnosis rate for breast cancer is 0.5%, which means that of every 1000 women who get mammograms 5 will be treated for breast cancer unnecessarily. This means that more people will be harmed by mammograms than will be helped.

I use mammograms as an example not because they have an especially high risk compared to other screening tests, but because clinicians and advocacy groups have promoted the benefits of mammograms with very little discussion of the risks. The same kinds of numbers hold true for colon cancer screening and even more for prostate cancer screening. Cervical cancer screening is a bit different. I will discuss all these screening tests in other posts.

Let’s return to the analogy of buying a lottery ticket. Suppose that in this lottery a small number of tickets contain explosives so that when you scratch one of these tickets to find your number it explodes causing serious injury. Would you participate in a lottery like that? You might, but only if your chance of winning we’re a lot higher than your chance of getting an exploding ticket.

For our health screening lottery that would be the case if you had a higher than average risk of having the disease being screened for. For example if your mother and your sister had breast cancer, then you certainly might take the risk of having regular mammograms.

For people at average risk for the disease being screened for, however, the chance of getting an exploding ticket is at least as high and for some tests higher than the chance of winning. Would you buy this lottery ticket?