Too Much of a Good Thing

Mel Cruger, 73, developed multiple myeloma in his 60s, enduring two bone marrow transplants and several years of often-harsh chemotherapy. He considered every available treatment option, took up many of them—and he prevailed.

Then in June 2010, nearly 10 years free of multiple myeloma, the Denver resident learned he had prostate cancer. This time, he didn’t choose aggressive treatment.

“Having been through multiple myeloma, this did not seem particularly life-threatening,” Cruger says. “Surgery seemed too radical. The question was whether the cure was worse than the disease.”

Cruger is among a growing number of people—from patients and caregivers to doctors and researchers—concerned about the balance between the risks posed by cancer itself and the risks of treatment. Several recent studies have documented “overdiagnosis” or “overtreatment” of people with certain types of early, slow-growing or low-risk cancers or even precancerous lesions—many of them picked up with increasingly sensitive tests.

It’s not just an issue in prostate cancer: People with papillary thyroid cancer live equally long with or without treatment, and women with ductal carcinoma in situ (DCIS), a non-invasive cancer, often choose aggressive treatment, even though nearly half of them will never go on to develop invasive disease and even fewer with a lumpectomy alone.

“There’s this idea that cancer is not something that you sit with, but not all cancers fit with this idea.”

“We have educated people that cancer is a lethal disease, that we must have this war against it,” says Grace Lu-Yao, PhD, of the Cancer Institute of New Jersey, co-author of a recent study that found overtreatment for early-stage prostate cancer, most cases of which were caught early by a PSA test and would never have triggered symptoms let alone threatened lives.

Yet Lu-Yao is not proposing abolition of the PSA test, which has—in some studies, but not all—been shown to save lives. Nor would she recommend eliminating mammograms, which can detect non-invasive cancers that most patients choose to have removed.

Instead, she and others who have studied the issue of overtreatment support giving patients the details they need to make informed decisions, especially when there are uncertainties about risks.

Jeffrey Belkora, PhD, of the University of California San Francisco’s Breast Care Center, says studies have documented the value of patient education in preventing overtreatment. One focused on women with breast cancer who were either given standard care—an informational pamphlet about “adjuvant” treatments—or who were guided through a patient-specific, evidence-based decision aid. Women with less severe tumors, for whom adjuvant therapy has low benefit, were less likely to choose that treatment (57 percent who used the aid versus 87 percent who received the pamphlet), the study showed.

“If you fully inform patients about their prognosis at early stage about the risks and benefits of adjuvant therapy, fewer patients end up having it,” Belkora says.

Cruger’s doctor had recommended regular PSA screens since 2001, when his PSA was elevated (although a subsequent biopsy turned up nothing). His PSA spiked in August 2009, then dropped in November and popped up again in May. This time, a biopsy turned up a small, inconspicuous spot.

In other biopsied sites, Cruger’s urologist did not find cancer. “He said, ‘You know, it doesn’t look very serious. You might want to consider active surveillance,’ ” Cruger recalls. In active surveillance of prostate cancer, doctors use PSA and other tests regularly to watch for significant changes.

Cruger started learning everything he could about prostate cancer. And then he talked: with his wife; his urologist; his oncologist; and his primary care physician, whose father-in-law had gone through a prostatectomy at a similar age as Cruger. “He had a very hard time,” Cruger says. “My doctor felt that for her father-in-law, the cure was far worse than the disease.”

In prostate cancer, treatment-related complications are common. One study documented that of men who had undergone a radical prostatectomy, more than 8 percent were incontinent and nearly 60 percent were impotent 18 or more months later. Also, hormone treatments can increase fracture risk, a major concern for older patients, Lu-Yao says. For older patients, in particular, that can mean the risk of dying from a disease or even experiencing disease symptoms is smaller than the risk of complications from treatment.

“Still, some people will say, ‘Oh my gosh, I have cancer! I have to get it out!’ ” Lu-Yao says.

Cruger says he didn’t feel that way. To him and his wife, the balance of evidence pointed in one direction: “We decided that this was something we should just watch.”

Michael Barry, MD, of the Massachusetts General Hospital in Boston and president of the Foundation for Informed Medical Decision-Making, says such decisions are rarely easy. While it is increasingly clear that early-stage prostate cancer is overtreated statistically, it is difficult or impossible to know who might benefit from treatment and who won’t.

“[The patient] may be destined to live another 30 years,” Barry says. “In that time, a low-risk, early-stage prostate cancer may have time to cause problems.”

But what if the patient has a very aggressive prostate cancer and dies of something totally unrelated the next week, he asks. In such a case, overtreatment for prostate cancer in low-risk men would at least be partly responsible for putting patients and doctors in a dilemma.

“Men who get regular PSA tests increase their risk of diagnosis somewhere between 50 and 70 percent,” he says, referring to data from a duo of screening studies published recently. “My guess is that if there were a vegetable that increased your risk of diagnosis to this level, no one would eat it.”

Results from two recent studies—one American, one European—came to somewhat different conclusions.

In the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, men in the prostate cancer arm were either offered annual screening or “usual care” (some ended up getting screened, some did not). Those screened were 22 percent more likely to be diagnosed but no more likely to survive prostate cancer after seven or 10 years.

In the European Randomized Study of Screening for Prostate Cancer, screening did confer a benefit but was also related to a high risk of overdiagnosis. The study, published in The New England Journal of Medicine, found “that 1,410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer.”

For early-stage thyroid cancer (papillary thyroid cancers limited to the thyroid gland) results are a bit clearer. Thyroid cancer diagnoses have tripled in the last three decades, primarily because of technologies that can pick it up early (ultrasonography and fine-needle aspiration). A study published in May 2010 showed that the 20-year survival of early thyroid cancer is very high regardless of treatment (often full or partial surgical removal sometimes followed by radiation). Survival was 99 percent for those treated; 97 percent for those not.

Joann Elmore, MD, a researcher at Harborview Medical Center in Seattle and a professor at the University of Washington, has focused her work on DCIS, a risk factor for developing invasive breast cancer (about half of women diagnosed with DCIS will ultimately be diagnosed with more invasive breast cancer, according to the National Cancer Institute). Although DCIS is not associated with any increase in mortality compared with the normal population, most women diagnosed with DCIS choose aggressive treatment, often lumpectomy, which risks scarring and infection.

“We have to be careful when discussing a diagnosis of DCIS with women,” Elmore says. “For some, the best treatment choice, given their personal values and preferences, may be to do as much as they can, even if that means risking overtreatment.”

Belkora agrees that patient-specific values—not just statistics—should guide treatment discussions.

“Patients could be at risk for overtreatment if their physician is not paying close attention to the patient’s own priorities,” Belkora says. Those priorities may depend on age, life situation, family, other health conditions and more.

Equally important is continued research into the factors that affect development of precancerous lesions and relatively low-risk cancers into higher risk versions, Elmore says.

“We need to [get] better at stratifying risk. Who goes on to have invasive cancer and who does not? That’s what we need to know.”

Scientists are tackling the issue through fields such as bioinformatics, which aims to characterize tumors by genetic and other fingerprints. Researchers at the University of California, San Francisco, for example, are trying to learn which patients are likely to see DCIS progress to invasive cancer and which are likely to never experience the more serious disease. The idea is to see if DCIS could be managed with active surveillance, much like prostate cancer.

Although it’s going to be a long-term project, Elmore says she’s hopeful. “We have amazing investigators looking at genetic markers and other risk factors, and we’re learning more and more.”