It’s time to start the cancer prevention revolution, according to Philip E. Castle, PhD, MPH, of the National Cancer Institute.

Castle and two other experts discussed the challenges and benefits of detecting precancerous lesions in the era of minimally invasive tests like liquid biopsies during a special session on Wednesday, April 13. The session, which can be viewed on the virtual platform by registered meeting participants through July 13, 2022, is titled Can Precancer Early Detection Become a Reality?

Castle said efforts to prevent cervical cancer could serve as a model for cancer prevention. Cervical cancer is “low-hanging fruit” because it has a single necessary cause, is slow growing, easily sampled, and has clearly defined precursors.

Ernest T. Hawk, MD, MPH, from MD Anderson Cancer Center, examined the promise and pitfalls of detecting precancerous lesions via multi-cancer early detection tests (MCEDs), or liquid biopsies.

Current recommendations specify that asymptomatic, average-risk adults should undergo regular organ-based cancer screening. However, these guideline-recommended tests are only available for breast, cervix, colon, lung, and prostate cancers, and about 70 percent of U.S. cancer deaths occur in sites without recommended screening options. This provides an exciting opportunity to expand early detection to more cancers using MCEDs, Hawk said.

In theory, multi-organ screening could be achieved by targeting any number of molecular markers in the blood or other organ effluents (e.g., saliva, urine, stool), and could potentially be cost-saving, Hawk said. However, early research into MCEDs suggests the potential need to examine the organ at risk, rather than the bloodstream, because the molecular signals from precancers can be remarkably faint.

“Each of the published studies highlights that these tests are better at finding advanced stages of cancer much more readily than early cancer,” said Hawk, noting that detection rates for stage 1 cancer typically range from 20 percent to 30 percent.

Another concern is whether detecting precancers using blood-based MCED tests will do more benefit or harm.

“Answering that question requires us to define the goals of such an endeavor—early detection of cancer/precancers at a single point in time, early detection of cancer/precancers over time, or improved risk assessment in the absence of cancer,” Hawk said.

“We are going to need comprehensive data and long-term follow-up of individuals to fully understand the implications of these sorts of screening tests. It may be best to focus efforts on high-risk cohorts,” he added.

Nickolas Papadopoulos, PhD, from Sidney Kimmel Comprehensive Cancer Center and the Johns Hopkins School of Medicine, discussed the use of liquid biopsies to detect precancerous lesions.

Blood-based liquid biopsies are easily accessible, are minimally invasive, and should be able to reach many demographics, Papadopoulos explained. But there’s a question of screening sensitivity and whether liquid biopsies will increase overdiagnosis and overtreatment. And most importantly, not every premalignant lesion will become cancer, Papadopoulos said.

“We have to have a way to decide which ones we need to detect and which ones we do not,” he said.

Papadopoulos and his colleagues developed a system to help identify pancreatic cysts that will progress to malignancy. To do this, they looked at the cyst rather than a blood test. By looking at the genetic profiles of cyst fluid and the tissue around the cyst, they developed markers to identify patients with cysts who could be safely discharged, who should be monitored, or who should be referred for surgery. The markers, combined with clinical features and imaging characteristics, were tested and validated with high sensitivity.

Their system, CompCyst, isn’t imperfect, Papadopoulos said, but it provided improved classification compared with the standard of care. In one analysis, CompCyst would have spared surgery for more than half of the patients who underwent unnecessary resection.

Based on these and similar findings in other disease types, blood-based detection of precancerous lesions will be challenging and could lead to significant overdiagnosis and overtreatment, Papadopoulos said. Instead, he believes that premalignant lesions may be best managed at the organ site.