The Counterintuitive Nature of Cancer Screening

 The first rule of cancer recovery is the extreme need for early discovery and treatment.  Researchers are continually seeking more accurate methods to deliver those early discoveries.  Yet, when physicians discuss cancer screening, they seem hesitant in recommending it, as if screening too often or too early might be bad for a patient.  Siddhartha Mukherjee provides a enlightening summary of the relevant issues in a The New Yorker article: The Catch in Catching Cancer Early.

Mukherjee tells the reader that several things must be recognized to understand the issues.  The first is that not all cancers are equal.  In fact, not all cancers are even dangerous.  Detecting them is one thing, responding to them is another.

“We have become adept at locating cancer’s physical presence—its corporeal form—but remain largely blind to its character, its behavior, its future. We employ genomic assays and histopathological grading, but many early-stage tumors remain biologically ambiguous. They might be the kind of early cancers that surgery can cure. They might be slow-growing and unlikely to cause harm. Or, most concerning, they might already have metastasized, rendering local intervention moot. Three possibilities—yet we often cannot tell which we’re confronting.”

The second concern that must be recognized is that there can be numerous false positives leading to unnecessary medical interventions that might risk the health of the patient.  Mukherjee uses the example of a group of 1000 smokers being screened with one case of cancer being present.  The screening procedure seems quite good with an accuracy of 99%.

“So what does it signify if someone in the group tests positive—what are the chances the person actually has cancer? Bayesian arithmetic gives a surprising answer: the test can be expected to identify the one person who actually has cancer, but it will also wrongly flag about ten people who don’t. That means there will be roughly eleven positive results, but only one of them is accurate. The chance that someone who tests positive has cancer, then, is just over nine per cent. In other words, eleven people would be sent for follow-up procedures, such as biopsies. And ten of them would go through a risky and invasive process—which can involve a punctured lung, bleeding, or other complications—with no benefit.”

It is critical that the statistical reality from this example be understood.  Apparently, it is either not understood, or it is being ignored.

“The consequences of ignoring these principles are staggering. In 2021, according to one estimate, the United States spent more than forty billion dollars on cancer screening. On average, a year’s worth of screenings yields nine million positive results—of which 8.8 million are false. Millions endure follow-up scans, biopsies, and anxiety so that just over two hundred thousand true positives can be found, of which an even smaller fraction can be cured by local treatment, like excision. The rest is noise mistaken for signal, harm mistaken for help.”

There are other statistical approaches that have been used to suggest that screening is always beneficial, but Mukherjee debunks them and concludes that the only way to show that screening works is to demonstrate that people who were screened actually live longer than those who were not.  This is a long and expensive process, but it has been done.

Colonoscopies have been proved to be beneficial as a screening process.  A colonoscopy is a rather risk-free process that allows a suspicious structure to be extracted as part of the procedure for detailed study after the fact.  The nature of the cancer can be identified if it is cancerous.

“The point isn’t that screening can’t pay off. The success stories are real. In 2022, The New England Journal of Medicine published the results of a landmark colonoscopy trial involving 84,585 participants in Poland, Norway, and Sweden. After more than a decade, the data showed an estimated fifty-per-cent reduction in deaths associated with colorectal cancer among those who received colonoscopies. Every four to five hundred colonoscopies prevented a case of colorectal cancer. The benefit was real—but demonstrating it required years of painstaking research.”

Not all endeavors have been so successful.

“The effectiveness of screening varies dramatically by cancer type. Consider ovarian cancer, a disease that often remains hidden until it has scattered itself across the abdomen. In 1993, researchers launched a major trial to test whether annual ultrasounds and blood tests could lower mortality. The scale was extraordinary: more than seventy-eight thousand women enrolled, half randomly assigned to screening. For four years, they endured transvaginal ultrasounds; for six years, routine blood draws. Then came more than a decade of monitoring.”

“And what did we learn? Among the screened, 3,285 received false positives. More than a thousand underwent unnecessary surgeries. A hundred and sixty-three suffered serious complications—bleeding, infection, bowel injury. But after eighteen years there was no difference in mortality. Even with three to six additional years of follow-up, the results held.”

 There is an intriguing opportunity to replace the current screening procedures with a simple blood test—simple for the patient at least.  As part of the normal cellular life cycle, cells die and spread their DNA in bits and pieces into the blood stream.  Researchers have determined that cancer cells go through the same process and DNA from cancerous tumors can be detected in a blood sample.  In principle one could detect the existence of cancer this way and also determine properties of the cancer that would provide an informed treatment plan.  Also, in principle, one could detect not just one form of cancer but screen for many options.  There are research teams out there trying to accomplish that and demonstrating potential for the approach.  It seems an incredibly difficult task, but one absolutely necessary.  Mukherjee details the state of progress and ends with guarded optimism.

“Perhaps, in time, we’ll build tools that can not only detect cancer’s presence but predict its course—tests that listen not just for signals but for intent. Early work with cell-free DNA hints at this possibility: blood tests that may one day tell us not only where a cancer began but whether it’s likely to pose a threat to health. For now, we dwell in a liminal space between promise and proof. It’s a space where hope still outpaces certainty and the holy grail of perfect screening remains just out of reach.”