Cancer terminology hasn't changed much over recent decades, but some experts say it's time for that to change, notes MedicalBrief.
In 2012, the US National Cancer Institute (NCI) convened a conference to discuss the over-diagnosis and over-treatment of indolent tumours – asymptomatic lesions unlikely to progress for years – that are detected by mammography, prostate-specific antigen (PSA) testing, and other screening tools.
The meeting participants’ first recommendation was to remove the word cancer from the names of tumours unlikely to become a problem. Instead, they urged, the tumours should be classified as indolent lesions of epithelial origin, or IDLEs.
Their reasoning? The word cancer generates fear and anxiety, which leads to over-treatment of tumours that are almost never associated with invasion and disease progression, explains Rita Rubin in JAMA Medical News.
She writes:
“We have this mentality that being aggressive surgically and fighting the cancer is the best thing, but a lot of the time it’s not,” said Laura Esserman, MD, MBA, director of the University of California-San Francisco, Breast Care Centre and the first author of a 2014 article by participants in the 2012 NCI brainstorming conference.
In the more than a decade since the conference, though, cancer terminology hasn’t changed much.
Two of the most common low-risk tumours bear the same name they’ve long had. Ductal carcinoma in situ (DCIS) is still called carcinoma. Grade group 1 (GG1), also called Gleason 6, prostate cancer is still called cancer, even though the authors of a recent article noted that it “is so highly prevalent it might be considered a normal feature of ageing”.
Still, Esserman, one of the most outspoken advocates of changing the nomenclature, remains optimistic about the chances of that happening. “I think we will see a change,” said Esserman, who in 2023 co-authored a New York Times opinion piece on the topic.
“I don’t know when it will be. Old theories often die when the people who espouse them do.”
Calling indolent tumours cancer can lead to over-treatment, but sceptics wonder whether the pendulum might swing too far the other way if such lesions didn’t have that label.
Meanwhile, most experts agree that no matter what low-risk tumours are called, patients in whom they’re detected need better information about their diagnosis before deciding how to proceed.
“We haven’t succeeded in putting ‘cancer’ and ‘doesn’t need to be treated’ in the same sentence,” noted Ruth Etzioni, PhD, a biostatistician at the Fred Hutchinson Cancer Centre’s Public Health Sciences Division.
Cancer by any other name
Although GG1 prostate cancer is still classified as cancer, most patients with that diagnosis don’t jump into treatment, a decision supported by guidelines.
GG1 prostate cancer is the least aggressive form of the disease. Pure GG1 prostate cancer – prostate tumours can be a mix of different grades – can’t metastasise, but it is a marker for coexisting or future higher-grade cancer, the authors of the recent article about it noted.
“For patients with low-risk prostate cancer, clinicians should recommend active surveillance as the preferred management option,” according to the joint guideline from the American Urological Association (AUA) and American Society for Radiation Oncology (ASTRO).
Even so, as of 2021, about 40% of US patients with prostate cancer who were candidates for active surveillance were still treated, although the rates varied widely among practices and practitioners, according to a 2023 article in JAMA Network Open. As the AUA and ASTRO guideline points out, all prostate cancer treatments carry risks, particularly related to urinary, sexual and bowel function.
However, of those patients who aren’t treated, many don’t undergo active surveillance either, suggested a 2016 study. Using the linked Surveillance, Epidemiology, and End Results Medicare dataset, the researchers identified more than 13 000 men with low-risk prostate cancer, nearly 3 000 of whom didn’t receive any treatment in the first year after their diagnosis.
Of the untreated men, 39% didn’t undergo any of three surveillance strategies – at least one prostate biopsy, four or more PSA tests, or four or more visits to a physician with prostate cancer listed as the diagnosis – in that first year. And untreated black men were more likely not to undergo surveillance than untreated white men.
The question is whether re-labelling GG1 prostate cancer as not cancer would encourage more patients to forego unnecessary treatment, one argument for renaming it, but also dissuade some from taking the need for active surveillance seriously.
For Esserman, who served on the GG1 working group that produced the recent article about whether the low-grade tumour is really cancer, the answer is clear.
“You don’t have to scare people to do surveillance,” she said. “You don’t have to have people get treatment they don’t need because they’re afraid of the name.”
But at least one of her colleagues in the working group disagrees.
Some patients diagnosed with GG1 prostate cancer have a “terrible-looking” magnetic resonance imaging scan, a strong family history of prostate cancer, or both, pointed out Adam Kibel, MD, chair of urology at Brigham and Women’s Hospital.
“Those are patients I wouldn’t want to tell, ‘It’s not cancer. Don’t worry about it’,” said Kibel, who co-authored a 2022 article that called reclassifying Gleason 6 prostate cancer as not cancer a “flawed” idea.
“The patients wouldn’t take it as seriously. The physicians wouldn’t take it as seriously.”
A 2023 study investigated the influence of the cancer label on the perception and management of GG1 prostate cancer. The researchers asked groups of healthy men, married women, and patients with GG1 whether they favoured continuing to call it cancer or changing it to a non-cancer label such as prostatic acinar neoplasm of low malignant potential, or simply calling it a tumour or growth.
All three groups favoured the non-cancer label and said they would be more likely to choose active surveillance if GG1 prostate cancer were to be reclassified. The authors cautioned that the theoretical nature of the study might have resulted in different choices from what participants would have made in real-life settings.
Discussions involving representatives of all interested parties are needed “to define the optimal terminology that does not misleadingly downplay erstwhile GG1 and the need to follow (active surveillance)vj protocols”, the researchers concluded.
Several months later, some of the same authors published the results of an international survey of approximately 1 300 urologists, radiation oncologists, pathologists, and medical oncologists about their perceptions of GG1 prostate cancer. About four out of five of them said they routinely recommend active surveillance for the disease. About four out of 10 felt reclassifying GG1 to a precancerous lesion was a good idea.
The remainder were split between disagreement with or uncertainty about the name change.
Challenging dogma
DCIS represents about 20% of the 300 000 new US breast cancer diagnoses each year, said Esserman, who noted that although DCIS is not invasive cancer, it is a risk factor for it.
In that respect, DCIS sounds a lot like GG1 prostate cancer. However, the option of active surveillance has not been on the table for women with DCIS.
“Everyone was so worried that if you didn’t operate on these patients, they would get cancer,” said Duke surgical oncologist Shelley Hwang, MD, MPH. So the conventional management of DCIS has been surgery and radiation followed by endocrine therapy.
Even so, Hwang noted: “I see plenty of patients who’ve already made the decision that they would prefer to do active monitoring.”
The problem was that until last month, no one knew what would happen if women with DCIS weren’t treated right away.
In December, Hwang and her collaborators presented the first results from a multi-centre US trial investigating that question. They reported their findings at the San Antonio Breast Cancer Symposium and in JAMA and JAMA Oncology.
Studies have shown that the cause-specific survival rate of patients with DCIS is 97% or 98%, raising the possibility that a similarly high survival rate could be obtained with a less-aggressive approach like active surveillance, noted an accompanying editorial in JAMA.
Hwang, the trial’s principal investigator, and her co-authors enrolled about 1 000 women who were 40 or older and had been newly diagnosed with hormone receptor–positive grade 1 or grade 2 DCIS without invasive cancer from 2017 to 2023.
The women were randomised to receive either active monitoring – follow-up every six months with breast imaging and physical examination – or guideline-concordant care. After two years, women who received active monitoring did not have a higher rate of invasive cancer in the same breast than those who got guideline-concordant care.
“We expect that with longer follow-up, there will be more invasive events, particularly in the active monitoring group,” the authors wrote, “and it is possible that the results reported in this analysis may be reversed when applied to a later time point.” For that reason, the trial will follow up with participants at five, seven, and 10 years.
“We never ever knew what would happen if we stopped doing it,” Hwang said of treating DCIS. The study, she said, challenged dogma. “We needed to challenge it, and, fortunately, the patients are very brave to do this.”
For now, the trial at least provides evidence that DCIS is not an emergency. “This is why I think it’s important to call it something else,” said Esserman, who was not involved in Hwang’s trial.
Esserman is a lead investigator on another trial, currently enrolling participants, that is seeking to determine whether hormone therapy and long-term active surveillance is effective in reducing the risk of ever developing invasive cancer in patients with hormone receptor–positive DCIS.
In Hwang’s trial, at least, the word carcinoma in DCIS did not seem to cause more anxiety in the trial participants who didn’t undergo surgery compared with those who did. The accompanying article in JAMA Oncology asked trial participants about their health-related quality of life, worries about DCIS, anxiety, depression and symptoms.
The researchers found that the responses were comparable between the active monitoring group and the guideline-concordant treated group, with fluctuations over time that weren’t clinically significant.
“I’m hopeful that this is an important step in the right direction,” Hwang said, adding that she’s been hearing from many women who are excited about her findings.
When a thyroid cancer isn’t
While the debate over reclassifying DCIS and GG1 prostate cancer as not cancer has bubbled for years, the re-labelling of one non-invasive tumor happened relatively quickly.
“This is generally not easy at all,” said Yuri Nikiforov, MD, PhD, a pathology professor and co-director of the Multi-disciplinary Thyroid Centre at the University of Pittsburgh School of Medicine. “We were kind of lucky.”
Nikiforov was the lead author of a 2016 article in JAMA Oncology that called for reclassifying a thyroid tumour from cancer to not cancer.
“There was a lot of thinking and planning involved to do this, to really be able to reclassify a cancer as non-cancer,” he explained. “It’s not enough to bring together experts and say, ‘Okay, these things we should not classify as cancer’. There has to be data.”
The tumour in question was called encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Although evidence was growing that EFVPTC was unlikely to become invasive, it usually was treated the same as conventional thyroid cancer, with a complete thyroidectomy and radioactive iodine to destroy any remaining thyroid tissue.
Patients then needed thyroid hormone replacement therapy for the rest of their lives.
One of the last straws for Nikiforov was seeing a 20-year-old patient who’d received the standard thyroid cancer treatment for this indolent tumour. “That’s enough,” he thought. “We are harming patients, but this is a disease that will never harm patients.”
To support their argument for the name change, Nikiforov and his co-authors conducted an international, multidisciplinary, retrospective study of more than 100 patients diagnosed with non-invasive EFVPTC who ended up having only the affected lobe removed, not the entire thyroid.
They had been monitored for 10 years to 26 years, and all of them were alive with no evidence of disease at the final follow-up.
The international team of authors called for renaming non-invasive EFVPTC as non-invasive follicular thyroid neoplasm with papillary-like nuclear features, or NIFTP. And in 2017, the World Health Organisation recognised NIFTP as a new term.
Compared with changing the name of low-risk DCIS or GG1 prostate cancer, “it was a little bit easier to do”, Nikiforov pointed out. “But people should keep trying.”
The main difference between NIFTP and the low-risk breast and prostate tumours is that “the diagnosis of NIFTP is established after removing half of the thyroid, so essentially no monitoring is needed”.
Since his 2016 report that supported reclassifying the non-invasive thyroid tumour as not cancer, “there are now multiple publications from different countries”, Nikiforov said. “In Europe and in the US, this diagnosis is issued every day, and patients are spared.”
The need for education
Debate aside, a tumour’s name is only the tip of the iceberg.
“I don’t think the name is that important,” acknowledged Hwang, who participated in the 2012 NCI conference about over-diagnosis and over-treatment. “It’s how we react to the diagnosis and how we convey risk to the patients.”
In other words, stop calling low-risk tumours cancer, but make sure patients understand that such lesions are risk factors for cancer and, therefore, require diligent monitoring. Or keep calling the tumours cancer, but make sure patients understand that these lesions are unlikely to cause problems, so active surveillance, not immediate treatment, is appropriate.
“The answer is to better help patients understand what cancer is – that cancer is not as scary as it used to be, that there are different types of cancer – to really make sure patients understand what they have,” Etzioni said.
Unfortunately, she added, that doesn’t appear to be happening. “I talk to women who had breast cancer. I say to them: was it in situ, or was it invasive? Often, they don’t know.” They might not realise that their breast cancer was low-risk DCIS, “and they’re walking around so anxious”.
The same goes for men with prostate cancer. Ask them about their tumour’s grade, and “they will say, ‘I don’t know’,” she said. “They know their PSA number better.”
Although Kibel opposes classifying indolent prostate tumours as anything but cancer, he acknowledged that “there is a care gap here where too many patients are undergoing treatment for something for which they could be safely observed. I actually completely agree…we’re over-treating prostate cancer”.
As Esserman emphasised: “The most important thing for us to do is to educate the public that cancer isn’t one disease.”
Study details
Patient-Reported Outcomes for Low-Risk Ductal Carcinoma in Situ: A secondary Analysis of the COMET Randomised Clinical Trial
Ann Partridge, Terry Hyslop, et al. Shelley Hwang, for the COMET Study Consortium
Published in JAMA Oncology on 12 December 2024
Abstract
Importance
Active monitoring (AM) for low-risk ductal carcinoma in situ (DCIS) has been considered as a potential alternative to guideline-concordant care (GCC; inclusive of surgery with or without radiation). Reported data comparing patient-reported outcomes (PROs) between GCC and AM for DCIS are lacking.
Objective
To compare PROs at baseline and over time in patients with low-risk DCIS randomised to receive either AM or GCC.
Design, Setting, and Participants
This prespecified secondary outcome analysis used prospectively collected validated questionnaires at baseline, 6 months, 1 year, and 2 years from participants enrolled from June 2017 to January 2023 in the Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) study for low-risk DCIS, which randomised participants to receive GCC or AM.
Intervention
Randomisation to GCC or AM.
Main Outcomes and Measures
Context-relevant PROs, including health-related quality of life, anxiety, depression, and symptoms measured by validated survey instruments. Mixed models, including sensitivity analyses, with group, point, and group-by-point effects were used to compare PROs between groups.
Results
Of the 957 participants in COMET, 225 (24%) were younger than 55 years at enrolment, 325 (34%) were aged 55 to 65 years, and 403 (42%) were older than 65 years, and 953 (99.5%) completed questionnaires at some point within the first 2 years, with a completion rate of more than 83% at all points. Quality of life, anxiety, depression, worries about DCIS, and symptom trajectories were comparable between groups, with modest fluctuations over time of limited clinical significance. Physical functioning was the only specific Medical Outcomes Study 36-item short-form health survey (SF-36) domain for which changes in the score trajectory differed by group over time, with mean scores ranging from 50 (baseline) to 48 (6, 12, and 24 months) in the GCC group and 50 (baseline) to 47 (12 months) and 48 (6 and 24 months) in the AM group (pooled SD, 9.9; P = .01), although these were also of limited clinical significance.
Conclusions and Relevance
In this prespecified secondary analysis of the COMET prospective randomised trial, the overall lived experience of women randomised to undergo AM for low-risk DCIS was similar to that of women randomised to GCC during the 2 years following diagnosis.
European Urology Focus article – Physician Perception of Grade Group 1 Prostate Cancer (Open access)
JAMA Oncology article – Encapsulated Follicular Variant of Papillary Thyroid Carcinoma
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