NCI group urges the medical community to address the increasing problem of cancer overdiagnosis and overtreatment


  • Carrie Printz

When Carl Raba, Jr, was diagnosed with prostate cancer in his mid 60s, he immediately thought the worst. “As a layperson, all cancers were the same to me, and all of them were deadly,” he says.

The father of 5, who at the time of diagnosis had recently lost his wife, was worried about being an “emotional burden” on his family. A surgeon told him he needed surgery, whereas a radiation oncologist advised radiation. Then, a good friend referred him to Ian Thompson, Jr, MD, director of the Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio.

Dr. Thompson presented a third option: wait and keep an eye on what appeared to be a very slow-growing cancer. Raba took his advice 10 years ago. He undergoes periodic examinations and biopsies and began taking the drug finasteride, which has been shown to reduce the risk of prostate tumors by about 30%. In that time, nothing has resurfaced that requires cancer treatment.

Patients such as Raba are one of the reasons why the National Cancer Institute (NCI) named Dr. Thompson and 2 other leading cancer researchers to a working group designed to address the increasing problem of cancer overdiagnosis, also referred to as identification of indolent cancer, which can lead to overtreatment. Dr. Thompson, along with Laura Esserman, MD, of the University of California San Francisco, and Brian Reid, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, recently published a commentary in JAMA.[1]

In the commentary, the authors say that “the word ‘cancer’ often invokes the specter of an inexorably lethal process; however, cancers are heterogeneous and can follow multiple paths, not all of which progress to metastases and death, and include indolent disease that causes no harm during the patient's lifetime. Although this complexity complicates the goal of early diagnosis, its recognition provides an opportunity to adapt cancer screening with a focus on identifying and treating those conditions most likely associated with morbidity and mortality.”

Cancer overdetection varies according to organ site, but prostate cancer has long been associated with the problem. For every case of aggressive disease that is detected, there are at least 5 to 10 additional patients who are treated unnecessarily for the disease, Dr. Thompson says. “When cancer is detected, the patient is labeled as a cancer survivor potentially unnecessarily,” he adds. “This leads to treatment or even surveillance and takes resources away from cancer treatment and diagnosis in patients who actually need it.”

He calls the problem of overdiagnosis, which has emerged as a result of appropriate use of better early detection methods, “a hard nut to crack.” Still, he and his working group colleagues urge the medical community to address it. Among the group's points is that physicians, patients, and the general public must begin to realize that overdiagnosis is common in breast, lung, prostate, and thyroid cancer. Screenings for these cancers leads to an increase in the number of these types of tumors that are detected.

Barrett's esophagus and ductal carcinoma in situ (DCIS) are examples in which detection and removal of precancerous lesions have not lowered the incidence of invasive cancer. Screenings for colon and cervical cancer, on the other hand, have helped to reduce incidence and late-stage disease.

Change in Terminology

Otis Brawley, MD, chief medical and scientific officer of the American Cancer Society, who has long called attention to this issue, says he's starting to see a shift in the medical community's attitude toward overtreatment. The topic of medical overdiagnosis, for example, was the subject of a conference held in September at Dartmouth University in Hanover, New Hampshire, and this year, the American Urological Association issued what Dr. Brawley calls “much more conservative” guidelines advising that men between the ages of 59 and 70 years undergo screening with informed decision-making about the risks involved. Previous recommendations suggested some men begin screening at age 40 years. “This is from the main people who make their living from treating prostate cancer—that's a good thing,” he says. “The definition of a professional is someone who puts the welfare and benefit of their patient above themselves.”

The NCI panel also recommended that a change in terminology be considered for some cancers. They suggest that the term “cancer” be reserved for lesions that are likely to progress if left untreated. Premalignant conditions such as DCIS and high-grade prostatic intraepithelial neoplasia should not be labeled as cancers, they say.

Under current nomenclature “these lesions suggest to patients that they have a life-threatening disease and should act accordingly,” Dr. Thompson says, noting that prostate intraepithelial cancer, for example, is rarely associated with prostate cancer, and scientists have not even confirmed if it is a premalignant process.

DCIS, meanwhile, has been overtreated for the past 20 years, Dr. Brawley says. Although 25 years ago the condition was not considered cancer, its detection increased significantly with the use of mammography: approximately 70,000 cases are diagnosed each year. The current recommended treatment for DCIS is mastectomy. “We don't know the natural history of DCIS as well as we think,” Dr. Brawley says. “We started treating it before we knew it needed treatment.”

Dr. Thompson and colleagues suggest that such cancers be reclassified as “IDLE” (indolent lesions of epithelial origin) conditions. A multidisciplinary effort across pathology, imaging, surgical, advocate, and medical communities convened by a group such as the Institute of Medicine could accomplish such a goal. A similar effort has already occurred in the bladder cancer community. In that case, the new terminology helped a number of patients avoid lifelong surveillance scopes of their bladders for “very low-grade lesions that almost never return or progress,” Dr. Thompson says.

New Methods of Detection

Although in certain cases there is still a slim risk of some of these indolent lesions progressing, Dr. Thompson believes many patients, if well informed, would not opt for treatment. “I tell my low-grade prostate cancer patients on a regular basis, ‘I’m not perfect—we're wrong maybe 2% to 3% of the time,'” he says.

In addition to the potential human costs of overtreatment, the financial costs are quite high, and range from $15,000 to $20,000 for treating prostate cancer, Dr. Thompson adds. Both he and Dr. Brawley see hope for improvement through projects such as the NCI's Early Detection Research Network, which is attempting to find biomarkers that will indicate which lesions are likely to do harm and how to interrupt their progression. For example, researchers are developing a blood test that could determine whether a suspicious lung nodule detected on a computed tomography scan is likely to progress and whether it should be removed. Already, such efforts are occurring in breast cancer with Oncotype DX, which tests 21 different genes and helps determine the aggressiveness of a patient's disease and how it should be treated. Similarly, in prostate disease, the PCA3 urine test is helping patients and physicians determine whether a biopsy is needed. “What will help us is genetic profiling of these cancers,” Dr. Brawley says.

Looking back, Raba is happy he chose active surveillance versus proceeding with treatment for his low-grade prostate cancer. “Had I not talked to Dr. Thompson, I definitely would have gone on to surgery or radiation,” he says, adding that he thinks cancer overtreatment is a problem. “I think it would be wonderful for people not to have to go through the emotional turmoil that I did.”

When cancer is detected, the patient is labeled as a cancer survivor potentially unnecessarily. This leads to treatment or even surveillance and takes resources away from treatment and diagnosis in patients who actually need it.

Ian Thompson, Jr, MD