The Asco Post

Tackling Overdiagnosis and Overtreatment, by Words and by Deeds  

By Charlotte Bath
September 15, 2013, Volume 4, Issue 15

The complexity of the pathologic condition called cancer,” according to a Viewpoint article in the Journal of the American Medical Association,1 “complicates the goal of early diagnosis.” Failure to recognize that cancers are heterogeneous, and that not all progress to metastases and death, can lead to overdiagnosis and overtreatment. Recognizing the complexity of the disease “provides an opportunity to adapt cancer screening with a focus on identifying and treating those conditions most likely associated with morbidity and mortality.”

The authors of the JAMA piece chaired a National Cancer Institute conference held to develop a strategy for improving the current approach to cancer screening and prevention, and they outlined their recommendations in the article. The recommendation that received the most attention in subsequent media coverage—which was considerable and included reports from The New York Times, The Washington Post, PBS, CBS, NBC, CNN, and FOX—concerned changing terminology so that the word “cancer” would be “reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated.”

Reclassify Some Cancers as IDLE

“There are 2 opportunities for change,” the authors wrote. “First, premalignant conditions (eg, ductal carcinoma in situ or high-grade prostatic intraepithelial neoplasia) should not be labeled as cancers or neoplasia, nor should the word ‘cancer’ be in the name. Second, molecular diagnostic tools that identify indolent or low-risk lesions need to be adopted and validated. Another step is to reclassify such cancers as IDLE (indolent lesions of epithelial origin) conditions.”

In an interview with The ASCO Post, Ian M. Thompson, Jr, MD, an article coauthor and working group Co-Chair, said that while he anticipated some resistance to the proposal to change cancer terminology, of all the recommendations, it is “probably the simplest to do.” Dr. Thompson noted that he and coauthor Laura J. Esserman, MD, MBA, initially proposed the term IDLE in an editorial published in JAMA in October 2009.2 “By changing our clinical and scientific priorities to focus on distinguishing indolent from aggressive disease, we can improve the value of screening, reduce morbidity of treatment, and prevent lethal outcomes of cancer,” they wrote.

“What we were saying,” Dr. Thompson said, “is what everyone knows is an inherent truism—that there are a lot of indolent tumors, more so in some organ sites than in others, and that by detection of indolent tumors, we don’t help our patients.”

The working group co-chairs specialize in cancers that figure prominently in the discussion of overdiagnosis and overtreatment. Dr. Thompson is a urologic oncologist and Director of the Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio, as well as Chair of the NCI Early Detection Research Network. Dr. Esserman is Director of the Carol Franc Buck Breast Cancer Center, Helen Diller Family Comprehensive Cancer Center, at the University of California, San Francisco. The third coauthor of the JAMA Viewpoint, Brian Reid, MD, PhD, is Director of the Seattle Barrett’s Esophagus Study at Fred Hutchinson Cancer Research Center in Seattle.

Terminology Matters

A study reported recently in JAMA Internal Medicine3 presented evidence that terminology can affect patients’ choice of treatment. In the study, 394 women without a history of breast cancer were presented with three scenarios that described ductal carcinoma in situ (DCIS) as noninvasive breast cancer, breast lesion, or abnormal cells. They were then asked to choose among three treatment options—surgery, medication, or active surveillance.

When DCIS was described as noninvasive cancer, 53% of the study participants favored nonsurgical options, but that rose to 63% when the term used was breast lesion, and 69% when the term used was abnormal cells. “We conclude that the terminology used to describe DCIS has a significant and important impact on patients’ perceptions of treatment alternatives. Health care providers who use ‘cancer’ to describe DCIS must be particularly assiduous in ensuring that patients understand the important distinctions between DCIS and invasive cancer,” the study authors wrote.

“That is the real world of this when you include the word ‘cancer,’” Dr. Thompson said. “Because the word ‘cancer’ has a connotation that is profoundly bad.” The word “precancerous” has that same connotation. “That means the shoe is going to drop sometime down the road and that you are irresponsible if you don’t do anything about it,” he continued.

“A multidisciplinary effort across the pathology, imaging, surgical, advocate, and medical communities could be convened by an independent group (eg, the Institute of Medicine) to revise the taxonomy of lesions now called cancer and to create reclassification criteria for IDLE conditions,” the NCI working group stated.

Refocus Screening

“Optimal screening frequency depends on the cancer’s growth rate,” the Viewpoint article noted. “If a cancer is fast growing, screening is rarely effective. If a cancer is slow growing but progressive, with a long latency and a precancerous lesion (eg, colonic polyps or cervical intraepithelial neoplasia), screening is ideal and less frequent screening (eg, 10 years for colonoscopy) may be effective. In the case of an indolent tumor, detection is potentially harmful because it can result in overtreatment. These observations provide an opportunity to refocus screening on reducing disease morbidity and mortality and lower the burden of cancer screening and treatments.”

One way to refocus screening is to consider the characteristics of the individual patient, Dr. Thompson said. “Do you want to do a screening CT scan on a nonsmoker who is 25 years of age? Probably not.”

Factoring in the life expectancy of the patient is also beneficial. “If a person has congestive heart failure, if you’ve looked at the life expectancy table, and the person has a life expectantly of 2 to 3 years, why would you draw a PSA test on that person?” Dr. Thompson asked. Another example involves colorectal cancer screening among the elderly. “That’s a classic example where the benefit, which might be 10 or 15 years down the road, is outweighed by the risks of the intervention,” Dr. Thompson said. “And then what do you do if you find something?”

Molecular Diagnostic Tools

Molecular diagnostic tools that can identify indolent or low-risk tumors are now available for “virtually every organ site,” Dr. Thompson said. Some of these molecular diagnostics “are approved and some are ‘home-brew.’ So they are not [U.S. Food and Drug Administration] registered, but you can have them done. There are dozens and dozens of these tools for each of the organ sites, and the trick is going to be to integrate them into prospective trials for validation.”

Using prostate cancer as an example, Dr. Thompson said, “If you select your patients properly for active surveillance—and that’s maybe 30% to 40% of all people diagnosed with prostate cancer—the risk of death in those patients is probably 1% to 2% in 10 to 12 years. The likelihood that any molecular diagnostic test will be able to pull out that 1% or 2% is incredibly low. So the molecular diagnostics need to be linked with current risk factors to determine when you use them. It is not just the molecular diagnostic, but it is the molecular diagnostic and its interaction with the patient and the tumor’s characteristics.”

Observational Registries

The NCI working group also called for observational registries for low-malignant-potential lesions. “Large registries for potentially indolent conditions would provide data linking disease dynamics (eg, tumor growth rate over time) and diagnostics needed to provide patients and physicians with confidence to select less invasive interventions,” the authors stated.

These large registries would be more representative of the entire population than current registries linked to academic centers, Dr. Thompson said. They could also provide information on how people in different parts of the country are responding to new recommendations about indolent cancers.

Not an Easy Undertaking

Dr. Esserman told The ASCO Post, “Since there is a growing recognition of the likelihood that we can safely do less, the opportunity, especially with DCIS, where we have always recommended surgical intervention, is to study the impact of doing less and learn for whom less aggressive strategies would be as effective.”

The NCI working group concluded, “Policies that prevent or reduce the chance of overdiagnosis and avoid overtreatment are needed, while maintaining those gains by which early detection is a major contributor to decreasing mortality and locally advanced disease.”

Now is the right time to do it, Dr. Thompson said, “simply because the science overwhelmingly says: As a nation, we overdetect disease. We are facing really significant challenges in managing a growing older population with limited resources. We can use those resources in a brute force manner without thinking about how we are helping people and completely bankrupt our nation—and, in the process, not help health outcomes. Or we can be much more intelligent, especially given the information that we know today, and use those resources for net good,” he continued.

“I think all of us would acknowledge that the process of doing this is not easy and it would require consensus groups getting together,” Dr. Thompson said. “It would require input from patients, as well as healthy members of the community. It would probably need to include people whose lives have been saved by screening and people whose lives have been affected by screening in adverse ways,” Dr. Thompson said.

“So it is a really big undertaking,” Dr. Thompson concluded, but “if we don’t pay attention to the overdiagnosis of indolent cancers, our lives may be profoundly changed, because we are taking very precious resources and putting them into efforts that cause harm and produce no benefit,” he stated. “It will be an expensive undertaking, and it will require an investment in prospective research studies that may not be completed for 20 years, but just because it is hard doesn’t mean that we shouldn’t be doing it.” ■

Disclosure: Drs. Thompson and Esserman reported no potential conflicts of interest.

References

1. Esserman LJ, Thompson IM, Reid B: Overdiagnosis and overtreatment in cancer: An opportunity for improvement. JAMA. July 29, 2013 (early release online).

2. Esserman L, Shieh Y, Thompson I: Rethinking screening for breast cancer and prostate cancer. JAMA 302:1685-1692, 2009.

3. Omer ZB, Hwang ES, Esserman LJ, et al: Impact of ductal carcinoma in situ terminology on patient treatment preferences. JAMA Intern Med. August 26, 2013 (early release online).

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