Management of complex renal cysts in Canada: results of a survey study

Background Bosniak III and IV cysts have a high risk of malignancy and have traditionally been managed surgically. However, growing evidence suggests that many can be managed by active surveillance. The main objective of this study was to characterize the use of surveillance in the management of complex renal cysts. Methods A web-based survey was sent to all registered, active members of the Canadian Urological Association (N = 583) in October 2018. Results The survey response rate was 24.7%. Management of Bosniak III cysts varied considerably. A large proportion of respondents (33.1%) offered active surveillance in > 50% of cases. Only 13.7% of respondents reported never or rarely (< 5% of cases) offering surveillance. In contrast, for Bosniak IV cysts, 60.1% of urologists never or rarely offered surveillance, while only 10.1% offer it in > 50% of cases. A significantly greater proportion of academic urologists, compared to non-academic urologists, viewed surveillance as a management option for patients with a Bosniak III or IV cyst. The most commonly reported barriers to a greater adoption of surveillance were concerns regarding its oncologic safety, the lack of data to support surveillance in this population, and the lack of triggers for discontinuation of active surveillance and intervention. Conclusions Despite active surveillance being included as a management option in guidelines, many Canadian urologists are reluctant to offer surveillance to patients with Bosniak III or IV cysts. Practice patterns are heterogeneous among those offering surveillance. High-quality studies are required to better define the benefits and risks of cystic renal mass surveillance.

The objectives of this survey study were to characterize the use of active surveillance in the management of complex renal cysts in Canada and to elicit the perceived barriers to adoption. We also aimed to characterize patient and disease factors associated with use of active surveillance and triggers used as criteria for intervention.

Methods
This is a descriptive cross-sectional study using electronic surveys and conducted based on known guidelines [19,20]. Following approval from the CIUSSS de l'Estrie -CHUS Research Ethics Board, a pilot questionnaire was developed and tested among 20 urologists in October 2018. All items were then revised according to the feedback received in the pilot survey. The survey questions were formatted as short answer, multiple choice, or Likert rating scale questions. Responses were anonymous and no personal information was collected or stored. An electronic open survey was generated on REDcap™ and distributed via email. The survey was distributed to all active members of the Canadian Urological Association (CUA) with a functional email address. Three emails (one initial and two reminders) containing a link to the English language questionnaire were sent out to all 583 members between October 30 and November 19,2018. Questions covered practice patterns regarding complex renal cysts, criteria used to select candidates for active surveillance, triggers to intervene in patients on active surveillance, and perceived barriers to a greater adoption of active surveillance (Additional file 1). In analyses, we excluded non-practicing urologists, urologists who reported not managing complex renal cysts, and urologists who gave incomplete demographic information or who did not answer questions beyond the demographic section.
Continuous and categorical variables were reported using medians (interquartile range [IQR]) and proportions, respectively. Chi-squared tests were used to assess differences between specific groups of respondents (types of practice). Statistical analyses were conducted using SAS/STAT® software, version 9.4. All statistical tests were two-sided and pvalues < 0.05 were considered statistically significant.

Results
In total, 144 urologists (24.7%) responded to the survey. From these, we excluded three urologists who were not actively in practice or did not manage complex cysts, and two urologists because they did not answer any questions other than demographics. Therefore, our study included 139 respondents, of which 88.8% (N = 122) answered every survey question.
Demographic data are presented in Table 1. Of the eligible respondents, 71 (51.1%) practiced in an academic center, while 68 (48.9%) practiced in a non-academic setting. The majority (87.0%) of respondents reported managing ≤20 new complex renal cysts on an annual basis.

Use of active surveillance
Of the eligible respondents, 13.7% of urologists never or rarely (< 5% of cases) offered active surveillance, while 33.1% offered active surveillance in > 50% of patients with a Bosniak III cysts in whom surgical excision is considered a suitable treatment option (Fig. 1). When compared to non-academic urologists, a significantly greater proportion of academic urologists offered active surveillance as a treatment option to their patients with a Bosniak III cyst. When patients with a Bosniak III cyst were offered active surveillance as a treatment option, it was perceived by nearly half of the urologists (45.7%) that this option was accepted in a majority of cases. The likelihood of a patient accepting active surveillance for the management of a Bosniak III cyst was perceived to be significantly greater by urologists from academic centres than by urologists from non-academic centres.
Unlike for Bosniak III cyst, a majority of urologists (60.1%) never or rarely (< 5% of cases) offered active surveillance for Bosniak IV cysts, while only 10.1% offered • > 30 8 (5.8) active surveillance in > 50% of cases. A significantly greater proportion of academic than non-academic urologists viewed active surveillance as a viable treatment alternative for patients with a Bosniak IV cyst. However, even when active surveillance was proposed to a patient as a treatment option, only 20.4% of urologists stated that this option was accepted by > 50% of patients.

Barriers to active surveillance adoption
Several potential barriers to a greater adoption of active surveillance were noted ( Table 2). The most commonly reported ones were [1] the patient's and physician's concerns regarding the oncologic safety and/or benefits of active surveillance (89.8%), [2] the lack of data supporting active surveillance in patients with Bosniak III-IV cysts (74.2%), and  [3] the lack of specific triggers for intervention during surveillance for complex renal cysts (75.8%).

Factors increasing likelihood of offering active surveillance
For both Bosniak III and IV cysts, age and the presence of comorbidities were perceived as having an impact on the likelihood of a patient being offered active surveillance as a treatment alternative ( Table 3). The majority of urologists viewed older patients (> 75 years of age) as being ideal candidates. Nevertheless, nearly 30% of urologists thought that the lower age cut-off should be 65 years old for patients with Bosniak III cysts. Likewise, most urologists viewed that cyst size influenced their decision to offer surveillance and that cysts < 4 cm were ideal for active surveillance. More specifically, for Bosniak III cysts, the presence of cyst wall nodularity (74.8%) and the maximal thickness of septa/calcification (44.1%) were also considered characteristics that impacted the likelihood of offering active surveillance. An upper limit threshold of 3 mm (IQR 2-5 mm) in maximal thickness of septa/calcification was perceived as being most appropriate for surveillance. For Bosniak IV cysts, the size of the nodular component was seen as important to the decision to offer active surveillance (69.9%) with a median perceived upper limit cutoff of 2 cm (IQR 1-3 cm).

Triggers for intervention during active surveillance
Several characteristics were perceived by urologists as being criteria for intervention for patients initially managed by active surveillance ( Table 4). The most commonly reported criteria for Bosniak III cysts were [1] progression on imaging from Bosniak III to IV cysts, [2] worsening or change in the wall or septa enhancement, [3] progression or development of cyst wall nodularity. For Bosniak IV cysts, the two most common triggers for intervention were perceived as being [1] the growth rate of solid component (> 0.5 cm/year) and [2] the growth of solid component (> 3 cm).

Surgical management
When managed surgically, over half of respondents (57.3%) were more likely to offer a minimally invasive partial nephrectomy approach to patients with a complex cyst as the surgical management of choice. No significant differences in terms of surgical management were observed between academic and non-academic urologists (Additional file 2). When compared to the management of small non-cystic renal masses, the majority of surveyed urologists managed Bosniak III and IV cysts in a similar fashion to how they manage small non-cystic renal masses. However, 20.7% of respondents were more inclined to offer an open surgical approach, while 14.6% were more inclined to perform a radical nephrectomy as opposed to a partial nephrectomy. Again, there were no statistically significant differences observed in the management of academic and community urologists (Additional file 3).

Discussion
Indirect evidence from the small non-cystic renal mass literature has supported the role of active surveillance as a management option for complex renal cysts [5,8,10,11,16,[21][22][23][24]. Two recent retrospective studies have also reported the outcomes of patients with a complex renal cyst who opted to be managed by active surveillance [17,18]. The average cyst sizes in the two studies were 4.1 cm and 3.5 cm for Bosniak III cysts, and 3.1 cm and 3.8 cm for Bosniak IV lesions, respectively. Both studies have suggested that this approach could be safely used in this population, with only one death due to kidney cancer observed after 5 years of follow-up in these studies. Moreover, only two patients with a Bosniak IV cyst developed a metastasis out of 243 patients with a Bosniak III or IV cyst (0.8%)both of whom had refused surgery despite evidence of local progression. Criteria for lesion progression included increase in cyst size, increase in vascularity, and increase in size of the solid component. Importantly, during the 5-year observation period, 65% of patients avoided surgery given the absence of lesion progression, and among patients who progressed, 16.5% were found to have a benign tumor on final pathology. While these results are encouraging, given the low quality of existing evidence, current guidelines on the management of complex renal cysts continue to recommend surgery as the mainstay treatment and suggest that the use of active surveillance should be reserved for select patients [6,16]. This study sought out to assess the adoption of active surveillance in Canada and to examine barriers to more widespread use. We found that approximately one third of Canadian urologists stated that they offered active surveillance as a treatment option in greater than 50% of patients who are diagnosed with a Bosniak III cyst, while only 10% of urologists offered surveillance in the majority of Bosniak IV cases. Importantly, over 60% of urologists did not consider or rarely considered active surveillance as a treatment option for a Bosniak IV cyst. Furthermore, the adoption of active surveillance for both Bosniak III and IV cysts was significantly greater among academic urologists compared to non-academic urologists. Likely reflecting the confidence of urologists for active surveillance, a greater proportion of urologists felt that, when offered to a patient, the chance of surveillance being chosen as management strategy was greater among patients diagnosed with a Bosniak III cyst than those with a Bosniak IV cyst.
When respondents were questioned on potential barriers preventing a more widespread use of active surveillance, the most common perceived concerns were [1] the lack of data supporting this strategy in this population, [2] the oncologic safety and benefits of active surveillance and [3] the lack of guidance on how to perform active surveillance and which specific triggers should be used to recommend discontinuation of active surveillance. We asked respondents what patient and tumor characteristics increased their likelihood of recommending active surveillance. As expected, a number of factors seemed to influence the urologist's decision, highlighting the fact that treatment decision for Bosniak III and IV cysts is a challenging one. We identified that a personal or familial history of kidney cancer, as well as the patient's treatment preference, influenced the likelihood that a physician would offer active surveillance. Multiple tumor characteristics also seemed to influence the likelihood of offering surveillance, with the most reported features being cyst size, size of nodular component, and presence of cyst wall nodularity. Importantly, the respondents also identified criteria perceived as triggers to offer discontinuation of active surveillance. For Bosniak III, the most common triggers were progression of cyst on imaging from Bosniak III to IV or development of cyst wall nodularity, and worsening or change in the wall or septa enhancement. For Bosniak IV cysts, the most common criteria identified were growth rate of solid component and overall growth of solid component. Interestingly, for both Bosniak III and IV cysts, the growth of the cystic component was not considered by most urologists as being worrisome enough to warrant treatment. Although this study offers insight into the current management of complex renal cysts in Canada, it is not devoid of limitations. First, the results are based on Canadian urologists' perceptions, and the identified criteria for initiation and discontinuation of active surveillance have never been properly studied. Therefore, the reported use of active surveillance may not necessarily be generalized to all clinicians' real-life practice. The reported patterns of active surveillance may provide a starting point for future studies, but criteria need to be validated before being applied in clinical practice. Second, there might be a selection bias in our cohort, as urologists interested in active surveillance of complex cysts may have responded to the survey more readily.
On the other hand, the study carries several strengths. First, the survey was pilot tested and validated by 20 experts in the field of urology. Second, the response rate to this survey was 24%, which is similar, and even higher than in other Canadian urology surveys [25,26]. Third, this study was designed, conducted and reported according to appropriate recommendations for survey research [19,20]. Most of the questions were structured in a closed format (binary, ordinal, nominal) in order to lower the bias of the responses.

Conclusions
This study supports that, despite the lack of high-quality evidence, many Canadian urologists offer active surveillance as an option to patients with complex renal cysts, especially if they have a Bosniak III cyst. However, the lack of sufficient data or guidelines on safety seems to prevent widespread adoption of active surveillance. Prospective studies should be conducted to provide evidence on the oncologic safety, benefits, harms, cost, eligibility criteria, and guidelines for the discontinuation of active surveillance in the management of Bosniak III and IV cysts.