NCI Panel: Stop Calling Low-Risk Lesions 'Cancer'

New Proposals to Reduce Overdiagnosis

Nick Mulcahy

July 30, 2013

The practice of oncology in the United States is in need of a host of reforms and initiatives to mitigate the problem of overdiagnosis and overtreatment of cancer, according to a working group sanctioned by the National Cancer Institute.

Perhaps most dramatically, the group says that a number of premalignant conditions, including ductal carcinoma in situ and high-grade prostatic intraepithelial neoplasia, should no longer be called "cancer."

Instead, the conditions should be labeled something more appropriate, such as indolent lesions of epithelial origin (IDLE), the working group suggests. The Viewpoint report was published online July 29 in JAMA.

"Use of the term 'cancer' should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated," write the 3 people who make up the working group — Laura Esserman, MD, MBA, from the University of California at San Francisco; Ian Thompson, MD, from the University of Texas Health Science Center at San Antonio; and Brian Reid, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle.

The group was charged with creating recommendations after a National Institutes of Health conference in March 2012.

They make a concrete proposal for change: "A multidisciplinary effort across the pathology, imaging, surgical, advocate, and medical communities could be convened by an independent group (e.g., the Institute of Medicine) to revise the taxonomy of lesions now called cancer and to create reclassification criteria for IDLE conditions."

This change of cancer terminology to reflect validated diagnostic tests that can identify indolent and low-risk lesions is 1 of 5 major reforms proposed by the working group. The scope of these initiatives ranges from cancer screening to cancer prevention.

The reforms are needed because, over the past 30 years or so, cancer screening in the United States has become highly problematic, the group explains.

At the heart of the problem is the fact that programs designed to reduce the rate of late-stage disease and decrease cancer mortality have not met these goals, according to the working group.

Instead, "national data demonstrate significant increases in early-stage disease, without a proportional decline in later-stage disease," they write.

Overdiagnosis occurs "when tumors are detected that, if unattended, would not become clinically apparent or cause death." If not recognized, overdiagnosis "generally leads to overtreatment," notes the working group.

Their Viewpoint mirrors, in a number of major ways, a 2009 essay by Drs. Esserman and Thompson that called for a "rethinking" of prostate and breast cancer screening, in part because of the overtreatment of indolent and low-risk lesions (JAMA. 2009;302:1685-1692). That essay prompted the chief medical officer of the American Cancer Society to famously declare, in an interview with a major news outlet, that "the advantages to screening have been exaggerated," which triggered a firestorm of controversy.

 
There is now an increasing consensus that overdetection and overtreatment are becoming real problems.
 

Has anything changed since 2009, when many of these ideas, including the nomenclature change, were prominently proposed by 2 members of the working group?

"What has changed...is that there is now an increasing consensus that overdetection and overtreatment are becoming real problems," Dr. Thompson told Medscape Medical News in an email.

The Other 4 Proposals

In addition to changes in cancer terminology, the 4 other major proposals are wide ranging and varied. The first is a public relations effort. "Physicians, patients, and the general public must recognize that overdiagnosis is common and occurs more frequently with cancer screening," the working group writes. "The trick is to provide the information evenly across all specialties and across the entire United States," Dr. Thompson explained.

Another proposal is to create observational registries for lesions with low malignant potential. This would improve information about related disease progression, which would help in the uptake of "alternative treatment strategies, such as active surveillance," the group explains. Dr. Thompson worries, however, that because registries are an expensive undertaking, they will be the "least likely" of the proposed steps to be implemented.

Another proposal by the working group — designed to "mitigate overdiagnosis" — includes an array of strategies to reduce the detection of indolent disease, such as reducing low-yield diagnostic evaluations appropriately, reducing the frequency of screening examinations, focusing screening on high-risk populations, and raising thresholds for recall and biopsy. "This is already happening," said Dr. Thompson.

"We can, for example, do a fairly good job before a biopsy of the prostate is performed of predicting what sort of tumor is most likely to be found (a slow-growing likely inconsequential tumor or a fast-growing lethal tumor)" with a risk calculator such as the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator.

Finally, the working group proposes expanding the "concept of how to approach disease progression." This concept would yield, ideally, alternatives to surgical excision by "controlling the environment in which precancerous and cancerous conditions arise," the group writes. "Strategies such as diet or chemoprevention may be as effective and less toxic than more traditional therapies in lower-risk tumors," Dr. Thompson explained.

Three Instructive Trends

Three instructive major trends — 2 negative and 1 positive — have emerged over the past 35 years as the United States has adopted more and more cancer screening, the group notes. The trends point the way to the creation of a useful paradigm for screening because they show under what conditions screening succeeds and fails, they write.

The first trend is that, in certain cancers, such as those of the breast and prostate, screening has led to an overall increase in incidence rates because both indolent and consequential tumors are identified. This a problem because screening "appears to detect more cancers that are potentially clinically insignificant." Lung cancer promises to create the same problem if high-risk screening is widely adopted, they assert.

The working group provides supporting statistics. In 1975, before mammography screening was prevalent, the incidence rate for breast cancer was 105 cases per 100,000 population. In 2010, the rate was 126 cases per 100,000 — an increase of 20%. Over that time period, there was a related 30% mortality decrease — from 31 to 21 deaths per 100,000. However, "at least two thirds of the mortality reduction is believed attributable to adjuvant therapy," they note.

The second trend is that screening expands the rate of indolent tumors, with "little or no effect on the small population of more aggressive tumors." The best examples of this are found in thyroid cancer and melanoma, the working groups reports.

Over the same 35-year period, the incidence rate of thyroid cancers jumped 185% — from 5 to 14 per 100,000. However, the mortality rate remained at roughly 0.5 per 100,000.

In addition, the incidence rate of melanoma rocketed up 199% — from about 8 to 23 per 100,000. But the mortality rate did not change much; it increased from 2.07 to 2.74 per 100,000.

The third trend is a positive one, according to the working group. Screening has "substantially" decreased incidence (through detection and removal of precursor lesions) and mortality, so the tumor population is "more homogeneous, slower-growing but consequential."

Colon and cervical cancer are the best examples of this. In each case, effective screening programs have led to "early detection and removal of precancerous lesions," which, in turn, have reduced incidence and late-stage disease.

The numbers bear out. The incidence rate of colon cancer dropped 31% from 1975 to 2010 — from about 41 to 29 per 100,000. The mortality rate dropped 45% — from 28 to 15 per 100,000.

The improvement in cervical cancer was even more dramatic. The incidence rate dropped 55% over the study period — from about 15 to 7 per 100,000. The mortality rate dropped 59% — from 5.5 to 2.2 per 100,000.

According to the working group, what can be learned from these 3 trends is that "optimal screening frequency depends on the cancer's growth rate." If a cancer is fast growing, screening is "rarely" effective. However, if a cancer is slow growing but progressive, with a long latency and a precancerous lesion such as colonic polyps or cervical intraepithelial neoplasia, "screening is ideal and less frequent screening (e.g., 10 years for colonoscopy) may be effective." Also, in the case of indolent tumors, detection is "potentially harmful because it can result in overtreatment."

Dr. Thompson believes that the "most important element" of their proposed ideas is "transparency." Clinicians need to communicate what is known about screening to patients. "Ultimately, they are captains of the ship; our job is to provide them with the navigation charts," he said.

"I agree with the premise of the article, and I agree in general with their suggestions," said Mikkael Sekeres, MD, director of the leukemia program at the Cleveland Clinic in Ohio, and chair of the US Food and Drug Administration Oncology Drug Advisory Committee, who was asked by Medscape Medical News for comment.

Low-risk myelodysplastic syndrome, which is classified by the World Health Organization as a neoplasma, is another example of a condition in need of a nomenclature adjustment, he said. Patients are often diagnosed with myelodysplastic syndrome as a result of a routine blood test taken by the primary care doctor; as a result, they live with a diagnosis of cancer but typically receive no treatment because the condition is low risk and without symptoms, Dr. Sekeres explained. "This is a very similar situation but is less well known" than the scenarios involving prostate-specific antigen testing or ductal carcinoma in situ found with mammography, he noted.

The working group hopes "that altering the semantics will reduce the anxiety brought about by one of these diagnoses," Dr. Sekeres told Medscape Medical News. However, substituting the word cancer with other terms is a "bit of a workaround," he noted. "What doctors should really be doing is communicating more effectively with their patients, and putting into context whatever finding they have."

Dr. Thompson reports serving as a board member or consultant for and receiving grants or grants pending, payment for lectures, patents, and honoraria from a variety of sources. Dr. Esserman and Dr. Reid have disclosed no relevant financial relationships.

JAMA. Published online July 29, 2013. Abstract

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