It’s All in the Name: Does Nomenclature for Indolent Prostate Cancer Impact Management and Anxiety?

Abstract

BACKGROUND:

Despite consensus guidelines, many men with low-grade prostate cancer are not managed with active surveillance. Patient perception of the nomenclature used to describe low-grade prostate cancers may partly explain this discrepancy.

METHODS:

A randomized online survey was administered to men without a history of prostate cancer, presenting a hypothetical clinical scenario in which they are given a new diagnosis of low-grade prostate cancer. The authors determined whether diagnosis nomenclature was associated with management preference and diagnosis-related anxiety using ratings given on a scale from 1 to 100, adjusting for participant characteristics through multivariable linear regression.

RESULTS:

The survey was completed by 718 men. Compared with Gleason 6 out of 10 prostate cancer, the term grade group 1 out of 5 prostate cancer was associated with lower preference for immediate treatment versus active surveillance (β = −9.3; 95% CI, −14.4, −4.2; P < .001), lower diagnosis-related anxiety (β = −8.3; 95% CI, −12.8, −3.8; P < .001), and lower perceived disease severity (β = −12.3; 95% CI, −16.5, −8.1; P < .001) at the time of initial diagnosis. Differences decreased as participants received more disease-specific education. Indolent lesion of epithelial origin, a suggested alternative term for indolent tumors, was not associated with differences in anxiety or preference for active surveillance.

CONCLUSIONS:

Within a hypothetical clinical scenario, nomenclature for low-grade prostate cancer affects initial perception of the disease and may alter subsequent decision making, including preference for active surveillance. Disease-specific education reduces the differential impact of nomenclature use, reaffirming the importance of comprehensive counseling and clear communication between the clinician and patient.

INTRODUCTION

Approximately 1,276,000 men were diagnosed with prostate cancer worldwide in 2018, many of whom had low-grade prostate cancer.^1,2 Guidelines recommend active surveillance as the preferred strategy for most low-grade prostate cancer given the low risk of prostate cancer mortality and to mitigate potential side effects of treatment.^3–5 However, a substantial proportion of eligible men do not pursue active surveillance.^6,7 Low-grade tumors were historically termed Gleason 6 out of 10 prostate cancer (Gleason). Although providers continue to use this term, patients may perceive this disease entity as aggressive because of the nonintuitive nature of a score of 6 representing the lowest risk disease and thus may opt for treatment in lieu of active surveillance.⁸ In 2014, the International Society of Urologic Pathologists revised the prostate cancer grading system, labeling the lowest-grade tumors as grade group 1 out of 5 prostate cancer (GG).⁹ More recently, some have suggested removing the label cancer from malignant neoplasms unlikely to be lethal without treatment, proposing terms such as indolent lesion of epithelial origin (IDLE) instead.^10,11 The purpose of this study was to assess how these 3 terms distinctively impact management decision making in an online survey presenting a hypothetical clinical scenario in which a man is newly diagnosed with low-grade prostate cancer. We hypothesized that the alternative terms to Gleason 6 out of 10 prostate cancer would be associated with higher preference for active surveillance (primary outcome) and lower anxiety (secondary outcome).

MATERIALS AND METHODS

Sample

After receiving Institutional Review Board approval from Northwestern University (STU00211525), an online survey (see Supporting Materials) open from April 20, 2020 to April 26, 2020 was administered to a convenience sample of men aged ≥40 years without a history of prostate cancer. The participants were recruited through ResearchMatch, an online national registry for recruitment to research studies.¹² Of the initial 16,326 participants invited by email to participate, 1054 agreed to participate and were randomized, and 718 (68.1%) completed the full survey and were included in the analysis. Study participants were promised the chance to be the random winner of a $100 Amazon.com gift card if they successfully completed the survey. The men were stratified by age and race and were randomized to 1 of 3 nomenclature groups. Participants in each group were presented with identical hypothetical clinical vignettes in which they received a new diagnosis of either Gleason, GG, or IDLE, based on their randomized assignment. Vignettes described basic prostate cancer risks, methods for diagnosis, the metastatic potential of low-grade prostate cancer, and the risks and benefits of active surveillance and treatment by either surgery or radiotherapy. Clinical vignettes were designed by 2 authors (A.S.D. and M.T.H.) and then were circulated among the remaining authors to confirm the accuracy and clarity of the information presented. The vignettes also were reviewed by nonphysicians for feedback on content and presentation.

Outcome Assessments

Participants used 100-point scales to rate their anxiety about their hypothetical diagnosis from 1 (not at all anxious) to 100 (extremely anxious) and to rate their preference for management of the condition from 1 (active surveillance) to 100 (treatment) at 3 time points: 1) immediately after the initial diagnosis, 2) after education on the low risk of metastatic progression, and 3) after education on the risks and benefits of management options. To account for multiple testing, we planned 1 primary outcome (difference in treatment preference) and 1 secondary outcome (difference in anxiety) after the first time point. At the conclusion of each of the 3 surveys, all participants were informed of the equivalence of all 3 nomenclature options in describing low-grade prostate cancer and were asked to explicitly rank their preference for each term (from 1 [do not prefer] to 100 [strongly prefer]), how much the nomenclature term affects or caused anxiety (from 1 [least anxiety] to 100 [most anxiety]), perception of disease severity (from 1 [not at all severe] to 100 [most severe]), and comfort with active surveillance (from 1 [least comfortable] to 100 [most comfortable]).

Statistical Analyses

Differences between group demographics were assessed using Student t tests and χ² tests. Multivariable linear regressions adjusting for baseline characteristics in Table 1 were used to determine the association between the 3 nomenclature options and the scores from 1 to 100 for our primary and secondary outcomes, with Gleason as the reference. The Sexual Health Inventory for Men¹³ and the American Urological Association Symptom Index¹⁴ were included to control for baseline urinary or sexual function issues that could impact a participant’s perception of risks and benefits of treatment versus active surveillance. Interactions between demographics and disease nomenclature on the primary outcome (difference in treatment preference) were assessed by performing additional multivariable linear regressions that included all baseline characteristics listed in Table 1 and an interaction term between nomenclature and either age, race, education, or income, in which annual income was categorized into 3 levels for simplification (≤$75,000, >$75,000, and unknown).

TABLE 1.

Survey Participant Characteristics

	No. of Patients (%)
Characteristic	Gleason 6 out of 10 Prostate Cancer, n = 243	Grade Group 1 out of 5 Prostate Cancer, n = 244	Indolent Lesion of Epithelial Origin, n = 231	P a
Age: Mean ± SD, y	60.6 ± 10.5	62.0 ± 11.3	61.6 ± 11.3	.38
Race				.24
White	214 (88.1)	226 (92.6)	208 (90)
Non-White	29 (11.9)	18 (7.4)	23 (10)
Education				.60
No college, some college, or associate degree	60 (24.7)	74 (30.3)	57 (24.7)
Bachelor’s degree	73 (30)	65 (26.6)	67 (29)
Postgraduate degree	110 (45.3)	105 (43)	107 (46.3)
Annual income				.56
≤$50,000	73 (30)	71 (29.1)	57 (24.7)
>$50,000-$75,000	31 (12.8)	38 (15.6)	47 (20.3)
>$75,000-$100,000	46 (18.9)	48 (19.7)	38 (16.5)
>$100,000	72 (29.6)	69 (28.3)	70 (30.3)
Unknown	21 (8.6)	18 (7.4)	19 (8.2)
Health insurance				.97
Public	67 (27.6)	64 (26.2)	69 (29.9)
Private	122 (50.2)	120 (49.2)	110 (47.6)
Combination of public and private	46 (18.9)	52 (21.3)	46 (19.9)
None	8 (3.3)	8 (3.3)	6 (2.6)
Charlson-comorbidity index: Mean	2.2 ± 1.6	2.4 ± 1.8	2.2 ± 1.7	.22
± SD SHIM: Mean ± SD	14.8 ± 2.8	14.8 ± 3.0	14.8 ± 2.8	.95
AUA-SI: Mean ± SD	8.0 ± 6.8	7.5 ± 7.4	8.2 ± 7.2	.53

Abbreviations: AUA-SI, American Urological Association–Symptom Index; SHIM, Sexual Health Inventory for Men.

^aDifferences were assessed using χ² analyses for categorical variables and the Student t test for continuous variables.

The Wilcoxon rank-sum test was used to compare responses regarding the term Gleason 6 out of 10 prostate cancer with the other nomenclature options after equivalence of the nomenclature was revealed. P values < .05 were considered statistically significant for no difference in anxiety and the likelihood of choosing surveillance between groups. All other analyses were considered exploratory. All calculations were performed using RStudio version 1.2.5019. Randomization and data collection were performed using REDCap (Vanderbilt University), an online survey data storage and management application.¹⁵

RESULTS

Baseline Characteristics

Of the 718 participants, 648 were White (90%), and the mean ± SD age was 61 ± 11 years. Most participants (73%) were college educated, and approximately one-half had an annual income >$75,000. There were no differences in baseline characteristics between randomized groups (Table 1).

Perceptions of Treatment Preference, Provoked Anxiety, and Disease Severity

Relative to Gleason 6 out of 10 prostate cancer (Gleason), the term grade group 1 out of 5 prostate cancer (GG) was associated with lower preference for immediate treatment compared with active surveillance at the time of initial hypothetical diagnosis when evaluated on a scale from 1 to 100, where 1 represents active surveillance, and 100 represents immediate treatment with either surgery or radiotherapy (β = −9.3; 95% CI, −14.4, −4.2; P < .001) (Fig. 1; see Supporting Table 1). GG nomenclature was also associated with less anxiety on a scale from 1 to 100, where 1 represents not at all anxious and 100 represents very anxious (β = −8.3; 95% CI, −12.8, −3.8; P < .001) (see Supporting Table 2). GG nomenclature continued to be associated with lower preference for treatment versus active surveillance after participants were informed of low metastatic risk (β = −6.9; 95% CI, −12.3, −1.4; P = .015), but it was no longer significantly associated with lower anxiety levels at this time point (β = −3.9; 95% CI, −8.8, 1.0; P = .121). After further participant education about the risks and benefits of the different management options, GG nomenclature was not significantly associated with either preference for treatment versus active surveillance (β = −4.7; 95% CI, − 9.7, 0.34; P = .067) or lower anxiety levels (β = −4.6; 95% CI, −9.2, 0.1; P = .053) compared with Gleason nomenclature. IDLE nomenclature was not significantly associated with anxiety scores or management preferences compared with Gleason nomenclature at any point during the survey. There were no statistically significant interactions between nomenclature and demographics (all P > .05) on preference for active surveillance over treatment. The declining effect of nomenclature choice on active surveillance preference and anxiety level scores as the participants learned more about the disease and treatment options reflects the similar high ranking that participants assigned to risks of treatments and benefits of active surveillance when asked to rank the factors most important to their decision making (see Supporting Fig. 1). GG nomenclature was associated with a lower perceived disease severity after initial diagnosis compared with Gleason nomenclature (β = −12.3; 95% CI, −16.5, −8.1; P < .001) (Fig. 2; see Supporting Table 3). This association persisted after participants were informed of the very low risk of metastasis leading to symptoms or death (β = −6.9; 95% CI, −11.6, −2.3; P = .004). IDLE nomenclature was not associated with a statistically significant difference in perceived disease severity at any time point during the survey.

Figure 1.

The association between nomenclature and hypothetical diagnosis-related anxiety and management preference is illustrated. The association between the randomly assigned disease nomenclature and diagnosis-induced anxiety and the likelihood of choosing active surveillance for management was assessed on a 100-point scale. Lower scores indicated less anxiety and higher likelihood of active surveillance (lower preference for surgery or radiotherapy). Vertical dashed lines represent the mean score of the entire study cohort. The median score for a given nomenclature group is represented by the notch of each horizontal box, whereas box width represents the interquartile range of scores. ^aAdjusted differences (Adjusted diff.) were calculated using multivariable linear regression adjusting for all covariates listed in Table 1.

Figure 2.

The association between nomenclature and the perception of hypothetical diagnosis severity is illustrated. The association between nomenclature to which each participant was randomized and apparent diagnosis severity was assessed on a 100-point scale, with lower scores indicating lower severity. Vertical lines represent the mean of the entire study cohort. The median score for a given nomenclature group is represented by the notch of each horizontal box, whereas box width represents the interquartile range of scores. ^aAdjusted differences (Adjusted diff.) were calculated using multivariable linear regression adjusting for all covariates listed in Table 1.

Explicit Comparison of Nomenclature

At the end of the survey, all participants were explicitly informed that Gleason, GG, and IDLE nomenclature all represented the same clinical entity—a low-grade prostate tumor with a very low metastatic potential. After revealing the clinical equivalency of the terms, participants were queried about their preference for each term and how each term affected their level of hypothetical anxiety, perception of disease severity, and comfort with active surveillance (Fig. 3). The survey cohort expressed a strong preference for GG nomenclature to describe the condition compared with Gleason nomenclature (P < .001). Participants also rated GG nomenclature as generating less hypothetical anxiety (P < .001) and lower perceived disease severity (P < .001) than Gleason nomenclature. GG nomenclature also scored higher for comfort with active surveillance (P < .001).

Figure 3.

The explicit assessment of each nomenclature option is illustrated. The final survey questions asked participants to assess multiple metrics for each nomenclature option, regardless of the nomenclature to which they were randomized. Comparisons were made between Gleason 6 out of 10 prostate cancer nomenclature using the Wilcoxon rank-sum test. Vertical lines represent the mean of the entire study cohort. The median score for a given nomenclature group is represented by the notch of each horizontal box, whereas box width represents the interquartile range of scores. Two asterisks (**) indicate P < .01; 3 asterisks (***), P < .001.

DISCUSSION

In a large survey study with >700 participants responding to a hypothetical clinical scenario in which a man is given a new diagnosis of low-grade prostate cancer, the use of GG nomenclature was associated with a lower preference for immediate treatment and, accordingly a greater preference for active surveillance, as well as less anxiety compared with Gleason nomenclature. The differences were most pronounced when survey participants first encountered the disease entity of low-grade prostate cancer and decreased as they received disease-specific education and counseling. The difference we observed in active surveillance preference and anxiety according to the nomenclature option used is not unexpected. There has been longstanding debate about including the term cancer in clinical descriptions of indolent prostate cancer because of the potential for negative perception by patients.¹⁶ Dixon et al demonstrated that disease label has a relative significant impact on potential treatment preference for thyroid lesions, especially if the term used did not contain the word cancer.¹⁷ It is notable then that IDLE, which does not contain an explicit reference to cancer, was not associated with differences in anxiety or preference for active surveillance and was not a preferred disease label term compared with traditional Gleason score nomenclature. This may be due to the complexity of the IDLE term, which could evoke an anxious response despite the absence of the term cancer. After revealing the clinical equivalency of all 3 terms, a few respondents gave IDLE a score of 0 or close to 0 on both the disease severity and anxiety scales, perhaps reflecting an accurate understanding of the term indolent in this subset of participants.

The preference for GG nomenclature observed in our study is in line with qualitative work performed by Loeb et al, who demonstrated that, in a group of 25 patients with prostate cancer, 88% preferred being a 1 on a scale of 1 out of 5 rather than a 6 in the Gleason scoring system.¹⁸ Seaman et al also demonstrated that the decision to pursue active surveillance is often a matter of the patient correctly identifying that the prognosis of the disease is favorable based on clinical factors such as prostate-specific antigen level, Gleason score, and magnetic resonance imaging results as well as being comprehensively educated on the risks, benefits, and alternatives to active treatment.¹⁹ Epstein and colleagues have suggested that use of the GG nomenclature can simplify a layperson’s understanding of the disease pathology and more concretely convey the low aggressiveness and metastatic potential of indolent prostate cancer.²⁰ A man with clearer insight into the spectrum of prostate cancer and potential outcomes may be less reluctant to pursue the guideline-recommended surveillance strategy. Although an optimal disease label is important, there is no substitute for the comprehensive knowledge and repeat counseling imparted by the clinician during shared decision making. In our study, the largest impact of nomenclature choice on treatment preference was at the time of initial hypothetical diagnosis. We demonstrated that, with increasing disease-specific education, nomenclature had less of an association with decision making and anxiety in our hypothetical vignettes. Although shared decision making and assessing a patient’s comprehension of their new diagnosis is critical, making the first impression count with straight-forward, accessible terminology can maximize what a patient takes away from that initial encounter.

Limitations

Our study is limited by several factors. We presented survey participants with a hypothetical clinical scenario. Although the information presented was consistent with what might be conveyed during an initial clinical consultation for a new diagnosis of prostate cancer, the format of the study inherently cannot capture the deliberative aspects and personal nature of the clinician-patient interaction that influence patient decision making. We discussed the risks and benefits of treatment and active surveillance in relatively general terms and were unable to address the nuances of treatment risk that may vary from clinician to clinician. We chose to survey men without a history of prostate cancer to reduce bias associated with prior knowledge of the disease. However, these men may not share the same concerns or have the same decision-making process as a man with an actual diagnosis of cancer. A man with prostate cancer may access numerous sources of information at the time of diagnosis (clinicians, web-based resources, decision aids) that use different nomenclature interchangeably, thus making it difficult to discern the effect of 1 nomenclature choice over the other in a real clinical encounter. We did not capture whether study participants had a history of surgery of any kind. A positive or negative past experience could bias their reported preference for management in our study. We did not assess the baseline anxiety level of a study participant before introducing the clinical vignette or whether or not the study participants had a friend or family member with a history of prostate cancer. Health literacy and numeracy also were not measured in study participants. These are all factors that could affect a man’s familiarity with disease grading, prognosis, and preference for different management options. However, the randomized design of our survey study mitigates the potential for bias introduced by unmeasured confounders to influence our results.

We solicited participant responses regarding anxiety and management preference using a scale from 1 to 100. This allowed for ease of data collection within the web-based platform but is not a validated measure and may be susceptible to response bias. For this reason, we encourage the interpretation of the score’s internal validity through the trends and associations observed within the study and caution against overinterpreting the individual scores themselves. In addition, there is selection bias inherent to all online survey platforms. A computer or mobile device and an internet connection are required for participation. The ResearchMatch cohort in general is overrepresented by White participants compared with the United States as a whole, and our study population also had a larger proportion who were college-educated.^21,22 These sociodemographic and economic factors are known to impact surveillance-related decision making,²³ and the composition of the survey cohort limits how our study results generalize to the national population.

Within these limitations, our findings suggest that nomenclature for low-grade prostate cancer affects perception of the disease and management decision making during an initial encounter and that the use of GG nomenclature for prostate cancer can increase preference for active surveillance compared with Gleason nomenclature. The differential effect of nomenclature is mitigated by disease-specific education, indicating that a thorough deliberation between clinician and patient regarding risks and benefits of treatment remains a critical driver of guidelines-conforming care.