An uncertain balance: In search of the sweet spot for cancer screening

After decades of aggressive cancer treatments, multiple studies have forced a reckoning of overtreatment for low-risk prostate, cervical, breast, and other cancers. Some studies of patients with low-risk prostate cancer managed by active surveillance, for example, have reported 10-year prostate cancer-specific survival rates of nearly 100%. A 2015 study, by contrast, found that of roughly 3000 men who had a life expectancy of less than 10 years and were diagnosed with low-risk prostate cancer, 67% had been overtreated.¹ In addition to averting the harm of increased treatment-related genitourinary and gastrointestinal toxicity, the authors wrote that “the ability to avoid treating the 80% of men with lowgrade disease who will never die of prostate cancer would save $1.32 billion per year nationally.”

Just as costly preventive care can lead to potential undertreatment and poor patient outcomes by undermining screening access and follow-up, overtreatment without clear evidence of benefits can contribute to avoidable harms and unnecessary costs for the US health care system.

The studies documenting continued overtreatment, however, raise important questions about whether such care is necessarily inappropriate in all cases and whether researchers have the tools needed to make that distinction. Researchers who spoke with CytoSource said that the decision-making often comes down to subjective judgment calls based in part on incomplete medical records, a lack of reliable risk stratification, limited high-quality imaging, conflicting guidelines, and strong patient preference. “This is the art of medicine, which is not very scientific,” says Sylvia L. Asa, MD, PhD, a professor of pathology at Case Western Reserve University in Cleveland, Ohio. “We’re not there yet.”

The ongoing controversy over how best to manage low-risk thyroid cancer offers one cautionary tale about the difficulty of finding the right balance. Dr Asa, for example, has found small incidental cancers in up to 24% of patients’ surgically resected thyroid glands. “They are very common,” she says. “They are readily accessible. People have palpation of their neck, we find something, they do an ultrasound, what we find clinically is probably completely irrelevant, but a small incidental cancer is identified and then panic ensues.”

On the basis of a diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), patients routinely underwent total thyroidectomy and received radioactive iodine as treatments. The treatments can offer clear benefits to patients with aggressive cancers but not to patients with low-risk disease, and neither intervention is risk-free. “The problem I worry about is that this is a disease of young people,” Dr Asa says. “We’re giving radiation to young people, many of whom are still planning to have a family and we say it’s safe, but let’s just say if it were my daughter or my son, I really would not be very happy about the idea.”

The vast majority of EFVPTC cases, as it turns out, are not a threat after all; despite a surge in diagnoses since 1975, the mortality rate has remained relatively flat. In response to the wave of overdiagnoses, expert panelists voted in 2016 to reclassify the noninvasive variant of EFVPTC as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).²

That renaming has proven controversial, though, even among some of the reclassification article’s coauthors, including Dr Asa, who contends that the attempt to “get rid of the C word” was solving the wrong problem. “I am not as concerned about overdiagnosis as I am about overtreatment,” she says. “I think there’s far less harm in knowing that there is something and understanding the biology of that than there is in not knowing. But there’s definitely a problem with overtreatment for a lot of things; people get scared, and we respond to fear rather than to knowledge.”

The messy realities of patient care have likewise intruded on consensus recommendations for other cancers. Since 1991, for example, medical associations have coalesced around the recommendation that clinicians can end cervical cancer screening in women who are 65 years old or older, are at average risk for the cancer, and have received three Papanicolaou (Pap) tests or two human papillomavirus cytology cotests within the past 10 years.

Even so, a recent study of female Medicare fee-for-service beneficiaries found that in 2019, more than 1.3 million still received a Pap test, colposcopy, or another cervical cancer screening–related service—approximately one in eight of the beneficiaries.³ Total annual screening costs exceeded $83 million despite the “unclear clinical appropriateness.”

The decision to stop cervical cancer screening can be confounded by big holes in the screening history of many patients that are exacerbated by the chronic lack of communication among electronic medical record systems. In some cases, Dr Holt has been able to see that a Pap test was done, but not its results. “These small little things are wrinkles that make it very difficult for doctors and health care providers to provide the correct care,” he says.

Medicare claims can provide a more complete data set, but they often do not sync up with previous health care records. Recent studies, in fact, have found that anywhere from 25% to 66% of patients 65 years old or older have not met the recommendation for an “adequate” cervical cancer screening history. Self-reporting of past cervical cancer screening is notoriously unreliable as well, with an accuracy rate of only 50%.

“Definitely, we need more studies that are investigating the harms of overscreening, but also the harms of underscreening: Are we missing cancers, and how many cancers are we missing because we’re not screening?” Dr Holt says. “It’s just a topic in an older population that has not been explored sufficiently.”

So far, the relative alignment of medical associations on cancer management guidelines has not been enough to resolve the issues of either overdiagnosis or overtreatment. A 2022 study found that 64% of physician survey respondents were still recommending overdiagnosis of thyroid cancer, with 40% recommending overtreatment.⁴

“Our data suggested one of the biggest contributors to overdiagnosis and overtreatment is concern about risk ofcancer recurrence,” says study coauthor Priya Dedhia, MD, PhD, an assistant professor of endocrine surgery at the Ohio State University in Columbus. Physicians who favored overdiagnosis indicated that peace of mind from a more extensive surgery influenced their recommendations, whereas separate data suggested that patient preference also played a role.

Ultimately, Dr Dedhia says, outcomes such as survival provide the best indicators of whether or not a cancer treatment regimen is appropriate. With a relative dearth of solid long-term survival data from randomized controlled trials, however, researchers point to other tools that might help to fill some of the knowledge gaps and provide a better balance in the meantime.

Dr Holt says that regulations requiring better interconnectivity of electronic medical records could give physicians a more complete view of a patient’s screening history. Dr Asa says that better imaging and risk stratification could likewise help physicians to make more informed decisions.

“For some of these scenarios, the question isn’t, ‘Should we treat it?’ It’s, ‘How should we treat it?’” Dr Asa says. “It’s really more a question of a rational risk-stratified approach to treatment that is tailored for the patient, as opposed to that all or nothing thing that we used to have.”