I have a very good friend in Shanghai, today their unit organized a physical examination, check out HE4 level is elevated. I was surprised to learn that HE4, known as human epididymal protein 4, is considered a sensitive marker for ovarian cancer and has been the subject of a number of studies. However, the hospital where I work is not yet able to carry out this test. It is surprising that a medical checkup center in Shanghai can offer such a “high-end” program. My friend, who is not very old and is doing fine, is very anxious about this “ovarian cancer marker”. Another time, in my clinic, a 65-year-old woman was repeatedly seen for a physical examination that revealed an elevated CA125, but nothing else. This visitor was also unusually anxious. She finally asked me to prescribe a gastroenteroscopy, which of course I respectfully refused, so she left, slamming the door with a ping-pong sound. I guess if I hadn’t been so gentle and calm, she would have yelled at the doctor for being unscrupulous. Slamming a door is nothing, hitting a doctor is what makes a man a man. Wouldn’t I be sensationalizing if I said that the vast majority of medical tests don’t improve life expectancy at all? It just so happens that last week’s BMJ published an analysis entitled: Why Cancer Screening Doesn’t “Save Lives”. The main reason the authors put life-saving in quotes is that studies have found that many cancer screenings do reduce disease-specific mortality (i.e., deaths from disease), but not overall mortality (deaths from all causes). For example, one meta-analysis of cancer screening found that 3 out of 10 studies were able to downgrade cancer-specific mortality, but did not reduce overall mortality. If both overall mortality and cancer-specific deaths were improved, then overall mortality improved more than cancer-specific mortality. Why is this? The authors suggest that there are two possible reasons: the studies were not weighted enough; and the downstream effects of screening are due. For example, in a 30-year rectal cancer screening study, fecal occult blood testing significantly reduced the incidence of colorectal cancer (128 vs. 192/10,000 people), but there was almost no difference in the overall mortality rate (7111 vs. 7109/10,000 people, P = 0.97). The study would need to be expanded to a 5-fold sample size if it were to achieve the 80% weighting of an overall mortality difference of 64 out of 10,000. In addition, the meta-analysis found that fecal occult blood testing significantly increased mortality from noncolorectal cancer, suggesting that the downstream effects of screening may also partially or fully influence the benefits of disease-specific mortality. Such “off-target deaths” in screening studies have been associated with false-positive rates, overdiagnosis, and so on. For example, prostate-specific antigen (PSA) leads to a significant number of false-positive results. Associated prostate biopsies can lead to very serious injuries, including hospitalization and death. In addition, more men diagnosed with prostate cancer die of heart disease or suicide the year after diagnosis, or even from complications of cancer treatment. The overall effect of cancer screening on mortality is compounded by the harms caused by further testing, overdiagnosis, and overtreatment, over and above those for tumors with well-defined target endpoints. As a result many cancer screening programs have been abandoned, such as chest radiograph screening for lung cancer, urine screening for neuroblastoma, and PSA screening for prostate cancer. The mortality benefits of screening studies need to be further examined. For example, low-dose CT screening in heavy smokers, while reducing the relative lung cancer mortality rate by 20% and the relative overall mortality rate by 6.7%, the absolute overall mortality rate was reduced by only 0.46%, and several serious deficiencies further limit this limited improvement. Not only did chest radiography fail to reduce specific or overall cancer mortality, but there is even a small body of evidence finding that lung screening increases lung cancer mortality. When studies are carefully screened, the improvement in overall mortality due to CT is not statistically significant. In addition, the incidence of serious complications outside of lung cancer mortality due to CT screening was more than twice that of overall deaths. A systematic evaluation found that patients who underwent CT screening did not have better survival times than controls. The systematic evaluation found that the public was overly enthusiastic about the benefits of screening and reluctant to accept its drawbacks. The study found that 68% of women believed that mammography reduced their low risk of breast cancer, 62% believed that screening reduced breast cancer by at least half, and 75% believed that 10 years of screening reduced the incidence of breast cancer by 10/1000. However, the most optimistic estimates of breast screening currently fall short of this level, and a Cochrane review found that PSA did not reduce prostate cancer-related mortality and mammography did not reduce breast cancer deaths. As a physician, you should be honest and objective about the uncertainty of cancer screening. The Swiss Medical Board does not recommend molybdenum imaging, and their evidence found that for every 1,000 women undergoing molybdenum imaging, only 1 more breast cancer case is added (from 4 to 5), but non-breast cancer deaths remain at 39 or even 40. If non-breast cancer deaths remain at the same level, women should weigh the pros and cons of screening. If screening leads to an increase in non-breast cancer deaths to 40, then screening women is nothing more than a reduction in one type of cause of death, at the cost of severe morbidity, anxiety, and expense. Studies of more than 600,000 women to date have not found that the breast cancer phenomenon reduces overall mortality. Screening studies have paid little attention to the associated damage. Only 7 of 57 studies quantitatively assessed overdiagnosis, and only 4% reported false-positive results. False-positive results of breast cancer screening are strongly associated with psychosocial distress, even 6 months after the diagnosis of breast cancer. More than 60% of women and 12-13% of men screened for PSA are affected by false-positive rates for more than 10 years. In a study of lung cancer (NLST), 39.1% had at least one positive result, 96.4% of which were false positives. In this study, 18% of patients diagnosed with lung cancer were overdiagnosed. And one-third of breast cancer patients were overdiagnosed. So how do we really know if screening is “saving lives”? It’s mostly a matter of the study sample. The researchers hypothesized that it would take 4.1 million participants in the Colorectal Cancer Screening Study to find that screening reduces overall mortality, compared to 150,000 participants in the Disease-Specific Mortality Study. Of course studies are incredibly expensive, but the economic benefits, once concluded, far outweigh the cost of the study. Political rights, economic resources, and public hospitals are often barriers to supporting full scientific inquiry. Achieving consensus on these issues also takes time and effort. There are no randomized controlled studies that have found cervical cancer screening to lead to a reduction in overall mortality, but epidemiology favors a benefit in this area (although there is no evidence). Studies of colonoscopy show a similar phenomenon. The current population tends to favor a decline in both prostate and breast cancer screening, but whether this is related to screening is unclear. Early breast cancer detection does not reduce the proportion of advanced disease. A meta-analysis of prostate cancer found that participants who are currently screened may not benefit from it. In summary, the authors concluded that for many people, it may be rational and sensible to reduce screening. As ACSO’s Chief Scientific and Medical Officer says: We must be honest about what we know, what we don’t know, and what we simply believe. Personally, I believe that the mysteries of life are vast and deep, and that there are many factors behind the great advances we have made in health and longevity. I personally believe that the mystery of life is vast and deep, and that there are many factors and driving forces behind our great advances in health and longevity. Worshipping faith in the power of modern medicine is not far from another kind of superstition. We need to objectively assess and honestly represent the costs, impacts and benefits of screening and medical examinations.