Researchers discuss ‘less is more’ cancer treatment approach

Mammography screening saves lives through early detection and treatment of invasive breast cancers, but it has also led to overdiagnosis and overtreatment of noninvasive ductal in situ carcinoma (DCIS), experts said at the American Society of Clinical Oncology (ASCO) Annual Meeting 2016, held June 3 to 7 in Chicago.

Esserman“Screening is more complex that we thought,” said Laura Esserman, MD, MBA, of the University of California, San Francisco, during the June 7 session, “Less Is More: A Multidisciplinary Conversation on Treatment Options.” The longstanding paradigm behind early detection and treatment was that carcinomas in situ “inexorably progress” to deadly cancers, she said.

An emerging alternative paradigm is that of “variable progression,” Esserman said: Some premalignant lesions do progress to become life-threatening cancers-and when progression occurs relatively slowly, early detection can indeed reduce mortality.

But other, “indolent” lesions, just don’t progress-and early detection and treatment won’t benefit patients.

By definition, DCIS lesions are non-invasive tumors. Most do not progress to become invasive, life-threatening malignancies. They’re indolent.

“DCIS is not yet a cancer-and might never become cancer,” agreed Fatima Cardoso, MD, of the Champalimaud Cancer Centre, in Lisbon, Portugal. “Indolent cancers exist and can be identified. Screening surfaces a reservoir of indolent conditions.”

The vast majority of women diagnosed with DCIS have excellent long-term prognoses, even without treatment.

Yet most women diagnosed with DCIS undergo surgery anyway. Many also receive radiotherapy, for which there is no evidence of improved survival among these patients, Cardoso said.

She blames a prevailing attitude of “when in doubt, treat.” Most patients hear the word “carcinoma” or “cancer” and believe they may die if they do not seek treatment, she said.

When cancer screening works-when it leads to early detection, diagnosis, and effective treatment-timelines for incidence rates of new diagnoses and mortality rates run roughly parallel to one another. That’s what has been seen with colorectal cancer (CRC) in the CRC screening era, Cardoso pointed out. Since the 1970s, both new diagnoses and mortality have declined.

But that’s not the case for thyroid cancers, Cardoso said. The incidence of thyroid cancer diagnoses has skyrocketed in Korea and elsewhere over the past decade, with the growing availability of thyroid screening. But thyroid cancer mortality hasn’t budged. Some researchers believe that’s because most of the screening-detected thyroid cancers are preclinical “incidentalomas” that would never have progressed to life-threatening tumors.

Data from the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER) show that as mammography screening rates increased since the 1990s, so did DCIS diagnoses, across age groups. The rates of DCIS treatment with surgery and radiotherapy have increased over that time, as well.

But there is little evidence of DCIS treatment-related declines in mortality over the same time period, presumably because so few DCIS lesions ever progress to become invasive malignancies.

Next: New research will offer better insight

Still, the evidence base for optimal DCIS management is small and mixed. Some population-based cohort data suggests that survival in low-grade DCIS is identically high (98%) whether women undergo surgery or observation only, Cardoso said. But other studies suggest that treatment might help some patients with DCIS, because a small minority of DCIS lesions do progress to become invasive tumors.

Well-designed, randomized, prospective research is badly needed to clarify optimal care for women diagnosed with DCIS, experts agreed.

Eun-Sil Shelley Hwang, MD, MPH, at the Duke University Medical Center in Durham, North Carolina, is leading just a prospective, randomized clinical trial, COMET, which aims to enroll 2,000 women diagnosed with low-risk DCIS to compare surgery (with or without adjuvant radiotherapy) against active surveillance with twice-yearly mammography.

The COMET study will provide urgently needed insight into DCIS management.

Meanwhile, Cardoso and others are calling for a change in the language cancer care professionals use to describe DCIS.

Dictionary.com defines cancer as both the malignant, invasive growth of a tumor, and “any evil condition or thing that spreads destructively,” Cardoso notes.

“Patients assume that cancer, left untreated, will kill you,” she said. “Physicians too!”

But clinically the word “cancer” today “encompasses many diseases with distinct trajectories,” she pointed out. “When nomenclature changes, treatment changes.”  

In an effort to facilitate a paradigm shift to reduce overdiagnosis and overtreatment of low-risk thyroid cancers, for example, researchers have proposed changing “encapsulated follicular variant of papillary thyroid carcinoma” to the equally cumbersome-but less threatening-sounding- “noninvasive follicular thyroid neoplasm with papillary-like nuclear features.”

It’s time for a reconsideration of nomenclature in DCIS, as well, Cardoso argued.

“Low-grade DCIS should not be called cancer,” she urged.