Key Points Study participants preferred the term grade group 1 (GG 1) over Gleason 6; they were less inclined to seek immediate treatment and preferred active surveillance when the GG 1 diagnosis was used. The term indolent lesion of epithelial origin (IDLE) was not viewed favorably by study participants and heightened their anxiety, perhaps because the words were difficult for them to comprehend.

When researchers asked study participants who were cancer-free to consider their reaction to a hypothetical diagnosis of low-grade prostate cancer with either a Gleason score (GS) of 6 out of 10 or an International Society of Urological Pathology (ISUP) GG of 1 out of 5, use of the latter terminology was associated with lower anxiety as well as a greater preference for active surveillance rather than unnecessary immediate treatment according to a new study published in Cancer (published online June 3, 2021. doi:10.1002/cncr.33621).

The ISUP introduced its prostate cancer GG system in 2014 as a replacement for the widely used, decades-old GS system. Nonetheless, some pathologists, urologists, and other clinicians still refer to a prostate cancer’s GS in pathology reports, in clinical notes, and in discussions with patients.

The original 1966 GS system ranked the microscopic appearance of the prostate on a scale of 2 to 10. However, by the year 2000, criteria for assigning a GS had changed so much that experts recommended never using a GS of 2, 3, or 4 in pathology reports of core biopsies (Am J Surg Pathol. 2000;24:477-478. doi:10.1097/00000478-200004000-00001), and even a GS of 5 was very uncommon for these specimens. This resulted in a situation in which a GS of 6 was often assumed to be on a scale of 1 to 10 (and, therefore, higher than “average”) when, in fact, 6 was essentially the lowest GS ever used for prostate biopsies.

It is widely agreed by clinicians that telling patients that they have a GS of 6 to describe their low-grade prostate cancer can be confusing and a barrier for patients to agree to active surveillance, says senior study author Shilajit D. Kundu, MD, chief of urologic oncology in the Department of Urology and associate professor of urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois, but the term is still fairly common. “This issue is important because how you present a new cancer diagnosis is critical for the patient’s initial mindset,” says Dr. Kundu. “Even though the diagnosis is the same, because the [GS] number 6 [out of 10] is higher [than GG 1 out of 5], the diagnosis seems worse and can cloud a patient’s decisions, leading to unnecessary treatment out of fear.”

Another part of the study investigated the effect of removing the word cancer entirely for a malignant neoplasm diagnosis and instead opting for the term IDLE. “So, the purpose of this study was to assess how these 3 terms (Gleason, GG, and IDLE) impact patients and their clinicians,” adds Dr. Kundu.

Study Details

The participants in the study were recruited from ResearchMatch (an online national registry of individuals interested in research study participation.) After 16,326 individuals were screened, 1054 agreed to participate, and the final analysis consisted of 718 men who were at least 40 years old and had completed the survey. Most of the 718 participants (73%) were college educated, 90% (648) were White, and their mean age was 61 years.

The men were randomly assigned to 1 of 3 groups and received the same clinical scenarios, but they were told that they had a GS of 6 out of 10, a GG of 1 out of 5, or IDLE according to their assignment. The participants rated their anxiety levels from 1 (not at all anxious) to 100 (extremely anxious) and their management preference from 1 (strongly prefer active surveillance) to 100 (strongly prefer immediate tumor-directed treatment) after each of the following: Receiving their initial diagnosis. Receiving written details about the potential for their low-grade prostate cancer to metastasize. Being informed about the risks and benefits of active surveillance and treatment by either surgery or radiotherapy.

After each survey was completed, the participants were told that each of the 3 terms was essentially identical and to rank their preference for each of the diagnostic terms from 1 (do not prefer) to 10 (strongly prefer). Additionally, they were asked to indicate which term caused the least anxiety (as low as a score of 1) and which terms caused the most anxiety (with a top score of 100) along with their perception of disease severity (from 1 [not at all severe] to 100 [the most severe]). They also were asked to gauge their comfort level with active surveillance, which ranged from 1 (least comfortable) to 100 (most comfortable).

Potential associations between the 3 terminology options and study options (anxiety, impression of disease severity, and treatment preferences) were analyzed by multivariable linear regressions with adjustments for participants’ demographic characteristics and health status (comorbidities and symptoms).

Study Results

Participants whose hypothetical prostate cancer was presented to them as GG 1 rather than GS 6 had lower diagnosis-related anxiety (β = −8.3; 95% CI, −12.8 to −3.8; P < .001) and said that they would be less inclined to seek immediate treatment and would prefer active surveillance (β = −9.3; 95% CI, −14.4 to −4.2; P < .001). They also indicated that, at the initial diagnosis, they perceived their prostate cancer was less severe if they were told that it was GG 1 instead of GS 6 (β = −12.3; 95% CI, −16.5 to −8.1; P < .001). The differences in anxiety associated with the 2 terminology options decreased as participants received more information about how uncommon it is for low-grade prostate cancer to evolve into metastatic disease.

When asked to compare GS 6 with the term IDLE, the participants did not indicate differences in the level of anxiety or preference for active surveillance versus immediate treatment.

Study Interpretation

“This study provides a heartening endorsement of success of one of the major overarching aims of the 2014 International Society of Urological Pathology consensus conference,” says Mahul B. Amin, MD, clinical professor of pathology at the University of Tennessee Health Science Center in Memphis, Tennessee, and adjunct professor of urology at the University of Southern California’s Keck School of Medicine in Los Angeles, California. “[This] was to revise and provide appropriate grading nomenclature for low-grade prostate cancers, thereby encouraging patients with potentially favorable outcome tumors to enthusiastically consider active surveillance, possibly preventing overtreatment by radical surgery or radiation therapy with their attendant complications.”

In an editorial accompanying the Cancer (2021;127:3290-3293. doi:10.1002/cncr.33619) study, Gregory C. McMahon, DO, an instructor in the Department of Urology at the Yale School of Medicine in New Haven, Connecticut, and Michael S. Leapman, MD, an assistant professor of urology at the Yale Cancer Center in New Haven, Connecticut, point out that the revised terminology is consistent with the growing emphasis on patient-centered outcomes. “These findings are in line with studies of barriers and facilitators of active surveillance, which have consistently highlighted the importance of a provider’s communications and their overall recommendation.”

Dr. McMahon and Dr. Leapman single out the term IDLE for criticism. “It is especially notable, then, that IDLE nomenclature did not meaningfully affect disease-related anxiety or preference for active surveillance relative to Gleason 6, end points that they have been explicitly designed to improve,” they wrote. “Despite not containing cancer, the term IDLE is laden with medical jargon, which may reduce comprehension and heighten uncertainty.”

Dr. Amin, who has served on several ISUP nomenclature panels, says that it has become increasingly clear that improvements in nomenclature can facilitate communication between clinicians and patients and help to guide adherence to evidence-based care. He notes that medical organizations periodically convene multidisciplinary teams of experts to review and update disease nomenclature. “[This effort yields] new nomenclature for unique clinico-pathologic entities recently recognized as distinct from other categories (for example, intraductal carcinoma of prostate, succinate dehydrogenase-deficient renal cell carcinoma, and micropapillary urothelial carcinoma), and has also revised the names of established entities based on updated prognostic data (for example, renaming most papillary transitional cell carcinomas, grade 1 of the bladder as ‘papillary neoplasm of low malignant potential’) to avoid the label of ‘carcinoma’ and more clearly denote that they have no potential to cause significant morbidity or mortality.”

Dr. Kundu says that it might require a little extra effort for some clinicians to change to the newer terminology and that they instead stick to using GSs because that is what they were taught. To improve patient comfort levels and understanding in weighing treatment options, however, he says that clinicians should make the switch if they have not done so already.