Shifting Tides: A Survey Analysis of Urologists' Evolving Attitudes and Practice Patterns in Focal Therapy for Prostate Cancer

doi:10.21203/rs.3.rs-4308182/v1

Purpose: Focal therapy (FT) is emerging as an alternative option to radical treatments for prostate cancer (CaP). The purpose of this study is to assess urologists’ current perceptions and utilization of FT.

Methods: A 22-item questionnaire was emailed to members of the American Urological Association. Multivariate logistic regression analysis was used to identify predictors of FT utilization. Results were also compared to a previous survey performed in 2017.

Results: A total of 264 responses were recorded. Less than half (115/264, 43.6%) of respondents utilize FT in their practice; among them, 42% perform FT on more than 10 patients/year. Common reasons for avoiding FT were diverse and included: lack of experience (51.8%), belief that CaP is multifocal (46.0%), and a lack of infrastructure (43.1%). The most commonly utilized modality for FT was high-intensity focused ultrasound (63.4%) followed by cryoablation (47.3%). Preferred patients selected for FT were primarily unilateral/anterior only Gleason Grade Group 2 (95/110, 86.4%). A fellowship training in urologic oncology (OR=2.86, p=0.008) and seeing more than 10 CaP patients per month (OR=2.46, p=0.002) were associated with greater utilization of FT. Most respondents (85.4%) cited better imaging methods as a factor that has increased FT utilization. Compared to a previous survey, a higher number of respondents (43% vs. 24%) utilize FT in their practice and more respondents believe in the "index lesion theory".

Conclusions: Less than half of the respondents utilize FT in their practice. Fellowship training in urologic oncology and a higher volume of CaP patients were correlated with FT utilization. As urologists gain more experience the trend of further utilization of FT for CaP may rise.

Prostate cancer

Focal therapy

Survey

Multiparametric MRI

Radical treatments (surgery or radiation) are considered the gold standard for localized prostate cancer.”(1). However, radical treatments significantly impact patients' quality of life (QoL), and genitourinary function and have been shown to be accompanied by a significant degree of treatment choice regret (2). The increasing use of diagnostic tools to localize and stratify prostate cancer (CaP) patients, such as multiparametric MRI (mpMRI), has led to the opportunity and desire for innovative focal treatments (3). In the past decade, focal therapy (FT) has emerged as a viable treatment option for selected men with biopsy proven clinically significant CaP confined to a section of the prostate and is associated with decreased morbidity compared to radical treatments (4). FT considers the spatial distribution of CaP within the prostate and treats the region of interest, thus minimizing the impact on quality of life (QoL) (5). Cryoablation, high-intensity focused ultrasound (HIFU), laser ablation, and irreversible electroporation (IRE) are the more commonly used energy modalities utilized in FT (6, 7).

A previous survey in 2017 addressing urologists’ views and utilization of FT found that 50.8% of respondents believed FT to be moderately to extremely beneficial in the management of CaP (8). The same survey indicated that only 24.2% of the respondents utilized FT in their clinical practice (8). Research continues to emerge, indicating that FT carries a low risk of adverse side effects and moderate efficacy in preventing CaP recurrence (9, 10). Considering the continuing adoption of FT, this study aims to provide an updated assessment of the views and practices of urologists regarding the use of FT in managing CaP.

2.1. Survey instrument

The survey instrument used in the previous study was adapted to a 22-item questionnaire with four questions and the elimination of two questions. The instrument was designed to collect demographic information and data on urologists’ perception and utilization of FT for localized CaP. Information obtained included: age, sex, practice type, geographical location, years in practice, fellowship training in urologic oncology, number of CaP patients seen in a month, and use of FT for CaP in clinical practice. Respondents were also asked if they believe in the index lesion theory as the basis for FT. The questionnaire was designed in a branching fashion so that respondents answered different follow-up questions based on how they answered the question regarding the utilization of FT. Also, some questions allowed respondents to “select all that apply” in response to a question. The survey instrument is included in the supplement.

2.2. Study design

A link to the survey was emailed to 22,415 members of the AUA in November of 2023. As the AUA has a heterogeneous member population (practicing physicians, research scientists, etc.), an unknown number of recipients qualified for the study, and therefore the response rate could not be accurately calculated. The responses were anonymously collected. All respondents consented to participate in the study. The study was reviewed and exempted by the institutional review board at the University of Cincinnati (IRB ID: 2023-0008).

2.3. Statistics

All statistical analyses were performed using SAS software (V9.4, SAS Institute Inc., Cary, NC). Univariate and multivariate logistic regression models were utilized to assess for predictors of FT use. Respondents’ age, practice type, years in practice, fellowship training in urologic oncology, number of newly diagnosed CaP patients per month, and whether the practice is based in the US were used in the regression analysis. Odds ratio and 95% confidence intervals were reported. The Chi-square test of independence was used to compare the results of three questions to the previous survey (8). The compared questions addressed the benefits of FT, belief in index lesion theory, and utilization of FT. All tests of significance were two-sided, and p-value < 0.05 was deemed statistically significant.

3.1. Respondent characteristics

A total of 264 responses were collected. The mean age of respondents was 52.9 (SD 14.4) years. The majority of respondents practice in the United States (181/257, 70.4%) and 55.3% have practiced for more than 15 years (141/255). 36.5% of respondents (93/255) were fellowship trained in urologic oncology and 38.1% (98/257) practiced in academic centers. (Table 1).

Table 1: Characteristics of survey respondents

Variable	Mean (SD) or n (%)
Age (n=264), mean (SD)	52.94 (14.4)
Gender (n=262)
Female	21 (8.0)
Male	240 (91.6)
Other	1 (0.4)
Practice Type (n=257)
Academic	98 (38.1)
Hybrid	50 (19.5)
Nonacademic	109 (42.4)
Practice based in the United States (n=257)
No	76 (29.6)
Yes	181 (70.4)
Years in practice (n=255)
0-5	41 (16.1)
6-10	44 (17.2)
11-15	29 (11.4)
>15	141 (55.3)
Fellowship Trained in urologic oncology (n=255)
No	162 (63.5)
Yes	93 (36.5)
No. of patents seen monthly with newly diagnosed prostate cancer (n=258)
1-10	133 (51.5)
10-20	80 (31.0)
20-30	27 (10.5)
>30	18 (7.0)

3.2. Survey responses

43.6% (115/264) of respondents utilize FT in their practice. 68% (175/257) of respondents answered that FT is moderately, very, or extremely beneficial. 59.4% (152/256) of respondents held belief in index lesion theory. Better imaging methods for localization of CaP was selected by 85.4% (217/254) of respondents as a factor that has increased the use of FT in the last five years. Most respondents (215/259, 83%) believe that FT will be a standard-of-care option in the future. Responses to survey questions are summarized in Figure 1.

Preferred candidates for FT were unilateral/anterior only Grade Group 2 for 86.4% of (95/110) respondents. The vast majority (89/111, 80.2%) of FT patients are selected via mpMRI and a combination of targeted and systematic biopsy. The three most common modalities utilized for FT were HIFU (71/112, 63.4%), cryoablation (53/112, 47.3%), and IRE (32/112, 28.6%). Most (68/111, 61.3%) of FT users attempt to repeat FT for a biopsy-proven CaP recurrence after FT. About half (57/110, 51.8%) of respondents using FT would utilize it more frequently if it could be performed in an office or outpatient setting (Table 2). Of the respondents that do not utilize FT, lack of experience (71/137, 51.8%) was the most frequent reason for FT avoidance (Figure 2).

Table 2: The respondents (n=115) who use focal therapy for CaP patients.

Question	n (%)
What set of prostate cancer patients are preferred (check all that apply)? (n=110)
Unilateral/anterior only Grade Group 1	53 (48.2)
Bilateral Grade Group 1 (as long as urethra and one neurovascular bundle are preserved)	24 (21.8)
Unilateral/anterior only Grade Group 2	95 (86.4)
Bilateral Grade Group 2 (as long as urethra and one neurovascular bundle are preserved)	27 (24.6)
Unilateral/anterior only Grade Group 3	52 (47.3)
Bilateral Grade Group 3 (as long as urethra and one neurovascular bundle are preserved)	11 (10.0)
Unilateral/anterior only Grade Group 4 or 5	12 (10.9)
Bilateral Grade Group 4 or 5 disease	1 (0.9)
How are Cap focal therapy candidates identified? (check all that apply) (n=111)
Ultrasound-guided systematic biopsy only (transperineal or transrectal)	13 (11.7)
Multiparametric MRI and systematic biopsy only (transperineal or transrectal)	17 (15.3)
Multiparametric MRI and targeted biopsy only (transperineal or transrectal)	13 (11.7)
Multiparametric MRI and a combination of targeted and systematic biopsy (transperineal or transrectal)	89 (80.2)
Template mapping biopsies with or without MRI	7 (6.3)
If a patient's prostate cancer can be treated with focal therapy, which age demographic[s] would you recommend focal therapy for? (check all that apply) (n=112)
40-49	53 (47.3)
50-59	79 (70.5)
60-69	97 (86.6)
70-80	94 (83.9)
>80	58 (51.8)
What modality? (check all that apply) (n=112)
Cryoablation	53 (47.3)
Laser ablation	9 (8.0)
High-Intensity focal ultrasound (HIFU)	71 (63.4)
Irreversible electroporation	32 (28.6)
Photodynamic therapy	3 (2.7)
Water vapor therapy	13 (11.6)
Radiofrequency ablation	2 (1.8)
Focal brachytherapy	13 (11.6)
Transurethral ultrasound ablation	4 (3.6)
Microwave ablation	1 (0.9)
On average how often do you perform focal therapy for prostate cancer? (n=113)
1-5 patients per year	36 (31.9)
6-10 patients per year	29 (25.7)
11-15 patients per year	16 (14.2)
>15 patients per year	32 (28.3)
How do you follow your patient's status post-focal therapy? (check all that apply) (n=111)
Prostate Specific Antigen/ PSA kinetics only	28 (25.2)
PSA plus multiparametric MRI followed by targeted biopsy only if there is a suspicious lesion	75 (67.6)
PSA plus protocol Biopsy at set intervals with or without prior multiparametric MRI	44 (39.6)
Do you attempt repeat focal therapy for biopsy proven recurrent prostate cancer post focal therapy? (n=111)
No	43 (38.7)
Yes	68 (61.3)
Which of the following should be part of the follow-up after focal therapy for prostate cancer? (check all that apply) (n=111)
Biopsies	83 (74.8)
PSA	108 (97.3)
Imaging	106 (95.5)
International Prostate Symptom Score (IPSS)	79 (71.2)
Sexual Health Inventory of Men (SHIM)	77 (69.4)
QoL questionnaire	60 (54.1)
Assessment of incontinence by # of pads	45 (40.5)
Would you use focal therapy more often if it could be performed effectively in an office or outpatient setting? (n=110)
No	53 (48.2)
Yes	57 (51.8)
Do you believe that navigation tools and treatment planning tools can improve focal therapy outcomes? (n=111)
No	4 (3.6)
Yes	87 (78.4)
Maybe	20 (18.0)

3.3. Prediction of focal therapy utilization

Fellowship training in urologic oncology (OR=2.86, 95% CI 1.57-5.22, P=0.001) and seeing more than ten newly diagnosed CaP patients per month (OR= 2.46, 95% CI 1.40-4.31, P=0.002) were independently associated with FT use. A practice based in the United States was associated with an increase of FT use on multivariate analysis (OR=2.44, 95% CI 1.27-4.67, P=0.008) (Table 3).

Table 3: Univariate and multiple logistic regression analysis for utilization of focal therapy

	Univariate		Multiple
Variable	OR [95% CI]	p-value	OR [95% CI]	p-value
Age	1.00 [0.98-1.02]	0.876	1.01 [0.98- 1.04]	0.692
Practice type
Nonacademic (reference)	-	-	-	-
Academic	0.97 [0.56-1.68]	0.517	0.67 [0.35-1.28]	0.080
Hybrid	1.32 [0.67-2.58]	0.352	1.30 [0.61-2.75]	0.187
Fellowship trained in Urologic Oncology (Yes)	2.50 [1.48-4.22]	0.0006	2.86 [1.57-5.22]	0.001
US-based practice (Yes)	1.43 [0.83-2.48]	0.198	2.44 [1.27-4.67]	0.008
Years in practice
0-15 (reference)	-	-	-	-
>15	1.04 [0.64-1.71]	0.871	1.10 [0.45-2.71]	0.830
No. of newly diagnosed CaP patients seen per month
1-10 (reference)	-	-	-	-
>10	2.51 [1.51-4.16]	0.0004	2.46 [1.40-4.31]	0.002

OR = odds ratio; 95% CI = 95% confidence interval.

3.4 Comparison to the previous survey

A higher number of respondents in the current survey believe in the "index lesion theory" and more respondents answered that FT is very and extremely beneficial (Table 4). Moreover, urologists are steadily increasing their adoption of FT; 43.6% (115/264) of respondents in the 2023 survey are using FT compared to only 24.2% (103/425) from the previous survey (p<0.0001)(Table 4) (8).

Table 4: Responses to 2023 survey questions compared to the previous survey.

	n (%)
Question	2023 Survey	Previous P values Survey^†
How beneficial is Focal therapy for CaP?	n=257	n=421 p<0.0001
No benefit at all	16 (6.2)	63 (15.0)
Slightly beneficial	66 (25.7)	144 (34.2)
Moderately beneficial	82 (31.9)	130 (30.9)
Very beneficial	69 (26.9)	68 (16.1)
Extremely beneficial	24 (9.3)	16 (3.8)
Belief in “Index lesion theory”	n=256	n=424 p=0.0004
No	104 (40.6)	232 (54.7)
Yes	152 (59.4)	192 (45.3)
Use focal therapy for CaP?	n=264	n=425 p<0.0001
No	149 (56.4)	322 (75.8)
Yes	115 (43.6)	103 (24.2)

†: Jain AL, Sidana A, Maruf M, Sugano D, Calio B, Wood BJ, Pinto PA. Analyzing the current practice patterns and views among urologists regarding focal therapy for prostate cancer. In Urologic Oncology: Seminars and Original Investigations 2019; 37 (3), 182-e1.

We need to demonstate some info in charts. Limit number of tables

As the technology for localizing CaP has emerged, opportunities for the growth of FT seem ripe, and this optimism is reflected in the confidence of urologists regarding FT captured in this survey.

The most importance difference between the current survey and the previous one is the higher rate of FT utilization among respondents (43.6% vs. 24.2%). The increase in adoption of FT might be related to newly graduated, fellowship trained urologists embracing this modality. In the previous survey, years of practice (> 15 yrs) was a significant predictor of the use of FT. In the current survey, fellowship training now significantly predicted FT utilization. Newly trained urologic oncologists may be driving increased adoption. In addition, increased utilization may be due to strong acceptance of the index lesion theory, as belief significantly increased from the previous survey (11–13). However, it remains to be seen if stronger belief in the index lesion theory is driving increased adoption rates, or if the emerging success of FT and viable short- and intermediate-term oncological outcomes are increasing support of the index lesion theory (4, 14). Regardless, much like in the previous survey, belief that CaP is multifocal still remains one of the top deterrents against adoption of FT utilization.

Furthermore, this survey reflects growing interest in FT modalities beyond HIFU, cryoablation, and IRE including water vapor therapy (WVA) and focal brachytherapy. In contrast, the previous survey results showed laser ablation and photodynamic therapy as the next two most commonly interested in modalities after cryoablation, HIFU, and IRE. Nascent research for WVA and focal brachytherapy may have peaked new interest within the urological community. In the world of WVA, the VAPOR 1 (15) trial showed effective cancer control (albeit in a small sample size of 15), and the ongoing VAPOR 2 (NCT05683691) may be poised to show effective long term control in a more substantive sample size. Furthermore, Matsuoka et al. found that focal brachytherapy offered far better control of genitourinary symptoms including continence and preserved ejaculation with similar salvage therapy free rates at 5 years compared to radical prostatectomy (16). As some FT modalities have demonstrated favorable oncological outcomes while causing minimal impact on genitourinary function and overall quality of life (17), new FT modalities are likely to emerge and enhance interest and adoption.

In multivariate logistics regression, having a US based practice is an independent significant predictor for the utilization of FT. This likely reflects a predominance of research on FT occurring in the US, with strong academic fellowships offering opportunities for graduating urologists to engage with FT. However, there is a large urology community studying and using FT outside of the US, especially in Europe. This survey only includes 76 individuals (29.6%) outside of the US. Therefore, limited sample size may contribute to trends seen here regarding global differences in use. In a survey from 2018 regarding the use of FT in the European urological community (with 88.4% of responses coming from European countries), 52% of survey respondents indicated they would recommend FT to a patient, with 70.8% believing FT will become a standard therapy option after certain refinements take place (18). There may be broader support for FT across both the United States and Europe, although this may not be accurately captured in this current survey.

Furthermore, although much research has gone into the patient selection and efficacy of FT, there is still confusion and debate on best practices for follow-up FT patients. Although a majority of urologists sampled use a combination of prostate specific antigen (PSA), mpMRI, and biopsy, a quarter (25.2%) are content with only using PSA trends Lebastchi et al. published consensus guidelines in 2020 that call for a systemic biopsy (along with targeted biopsy) at 6–12 months post FT, although they do not call for an extended 5 year timeframe sample (19). Furthermore, there is less agreement on the necessity of including functional and QoL metrics (SHIM score, AUA-SS and QoL questionnaires) on urologists polled in this survey. In contrast, Lebastchi et al. called for the necessity of investigating functional outcomes 3–6 months after FT and until resolution of noted symptoms (19). A lack of universal guidelines for follow up after FT may make new providers hesitant to begin using FT and provide a major hinderance in comparing FT outcomes in patients across varying centers.

This survey was limited by a small sample size, which limits the ability to draw generalizable conclusions on the attitude of urologists as a whole toward FT. Other limitations include the inability to calculate an accurate response rate and the unknown characteristics of those who chose not to respond. Presumably, there could be a considerable amount of respondent bias, as those who are more familiar with FT could be more likely to respond to a FT survey. Nonetheless, this survey still gives a glimpse into the changing landscape of the CaP field in regard to FT.

There is increasing confidence and adoption of FT by the urologists polled in this survey, with fellowship training significantly predicting the use of this modality. There is still considerable debate over the merit of the index lesion theory, and although belief is growing, it still heavily contributes to resistance to FT adoption. Witnessing the optimism of the urologic community in FT is exciting, and ongoing positive data may continue to drive further adoption.

The authors of this paper have no competing interests to disclose.

Funding

The authors of this paper have no funding to disclose.

Author Contribution

A.G. and A.S. were primarily involved in conceptualization. J.K. and S.T. conducted project preparation and management of the data. W.H. performed the formal data analysis. J.K. conducted the investigation. J.K. and V.V. wrote the original draft. A.L., A.S., and J.K. were involved in review and editing.

Data Availability

The full data from the survey can be found in a google sheet at the following link: https://docs.google.com/spreadsheets/d/1xRkiZx1kMnkmSqXK99g9jsIG6pepklagaXB1xEuivJA/edit?usp=sharing

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No competing interests reported.

UrologistFocalTherapySurveyQuestions.docx

Shifting Tides: A Survey Analysis of Urologists' Evolving Attitudes and Practice Patterns in Focal Therapy for Prostate Cancer

Status:

Version 1

Abstract

Figures

1. Introduction

2. Materials and Methods

2.1. Survey instrument

2.2. Study design

2.3. Statistics

3. Results

4. Discussion

5. Conclusions

Declarations

Funding

Author Contribution

Data Availability

References

Additional Declarations

Supplementary Files

Status:

Version 1