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What we choose to call cancer may shape patients’ behavior in ways that influence their health outcomes. Relabeling low-grade prostate cancer as a precancerous condition, for instance, could reduce prostate cancer deaths under most modeled scenarios, according to a new modeling study published in JAMA Oncology.

The model assumes that dropping the cancer label for grade group 1 disease would increase screening uptake among some men by reducing concerns about overdiagnosis and overtreatment. As a result, more clinically significant cancers could be detected through screening, potentially reducing prostate cancer deaths. On the flipside, however, men diagnosed with a precancerous condition might drop out of active surveillance, leading to more prostate cancer deaths in that population.

Under the study’s base case, nearly 2400 prostate cancer deaths were avoided, the authors reported. More specifically, relabeling would avert 2835 prostate cancer deaths through increased screening, whereas 452 more men would die as a result of dropping out of surveillance.

“We show that the number of deaths caused by relabeling, due to less adherence to active surveillance, is far less than the number of deaths avoided by relabeling leading to more screening,” said corresponding author Andrew Vickers, PhD, a biostatistician at the Memorial Sloan Kettering Cancer Center in New York City.

Whether low-risk pathology should be called cancer is a matter of debate in several settings, including breast and prostate cancer. Some pathologies that meet histological criteria for malignancy but are not lethal have been renamed to stress their indolence, Otis W. Brawley, MD, a professor of oncology at the Johns Hopkins University School of Medicine in Baltimore, explained in an accompanying editorial.

In prostate cancer, however, the debate continues. While Vickers and one outside expert felt the new work supported relabeling, others were less convinced.

“If relabeling has zero effect on screening rates then their finding of a benefit goes away,” said Ruth Etzioni, PhD, a biostatistician at the Fred Hutchinson Cancer Center in Seattle, who studies early detection of prostate and breast cancer. That means it’s critical to understand whether men are not being screened because they’re worried about overdiagnosis, Etzioni said.

In the modeling study, researchers estimated the effects of relabeling under six scenarios. The model assumed that redefining low-grade prostate cancer as a precancerous lesion would increase prostate cancer screening uptake. The scenarios also assumed that prostate cancer screening and treatment would reduce prostate cancer deaths and that high-quality screening and treatment would be widely available, Brawley noted in his editorial.

In the base case, the model assumed 100,480 diagnoses of grade group 1 prostate cancer, that 36% of patients would require treatment at 10 years, and that the surveillance dropout rate would increase by 25% due to relabeling. The model also assumed an absolute risk reduction of 5 percentage points with treatment, based on randomized trial data. Finally, the team assumed relabeling would cause a rise in screening rates of 15 percentage points (currently, about 38% of men aged 50 years or older are receiving screening in the US).

The model projected a net reduction in prostate cancer deaths in five of six sensitivity analyses, with deaths averted ranging from 115 to 2665.

In one scenario, however, relabeling led to an extra 823 net deaths. Vickers and his colleagues explained that they were able to “reverse” the positive findings “only under a set of extreme assumptions, including the absolute risk reduction of treatment in patients receiving active surveillance who progress being extreme (10%).”

Overall, Vickers viewed the findings as supporting relabeling. “My own personal view is that we have had the argument, and it is over,” he said.

Grace Lu-Yao, PhD, MPH, an epidemiologist and a professor of medical oncology at the Thomas Jefferson University in Philadelphia, said the model appeared “reasonable, and the extensive sensitivity analyses support its robustness.” The results suggest that, if this relabeling influences clinical behavior, it may reduce overtreatment and save lives, she said, who was not involved in the research.

The work is relevant beyond prostate cancer, Lu-Yao added. Advances in detection technology such as multi-cancer detection tests “are now outpacing our biological understanding of which lesions are truly life-threatening,” she said, making correct labeling all the more important. “Otherwise, the harms of overdiagnosis and overtreatment of precancerous lesions may outweigh the benefits.”

Gilbert Welch, MD, a general internist at Brigham and Women’s Hospital in Somerville, Massachusetts, who has written about screening for decades, said the increase in screening “is just that: an assumption.”

The big picture, in his view, is that “relabeling will have little effect on prostate cancer mortality and would reduce overdiagnosis or overtreatment. That’s good.”

What’s less clear, he added, is whether pathologists will change their diagnostic thresholds in response to relabeling. In other words, “will they be more likely to call a GG1 a GG2 to ensure treatment and lower their perceived failure-to-diagnose risk?”

The study had no commercial funding. Vickers reported receiving royalties from a test used to help detect prostate cancer. Welch reported receiving royalties from three books including Should I be tested for cancer?

Etzioni and Lu-Yao reported having no financial disclosures.