Genitourinary Imaging
Original Research
Outcomes and Complications Related to the Management of Bosniak Cystic Renal Lesions
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OBJECTIVE. The objective of our study was to evaluate outcomes and complications related to the management of Bosniak category IIF, III, and IV renal cysts.
MATERIALS AND METHODS. For this multiinstitutional retrospective study, a Web-based Research Electronic Data Capture (REDCap) data registry was used to record data of 286 adult patients with 312 prospectively classified Bosniak IIF, III, and IV renal cysts diagnosed between January 2000 and October 2011. Included patients were managed by surgery (n = 86), percutaneous ablation (n = 19), or imaging surveillance of 1 year or more (n = 181). The median number of years of clinical surveillance was 2.4 years (range, 0–11.7 years), 2.6 years (range, 0.4–11.4 years), and 3.2 years (range, 1.1–11.6 years) for patients managed by surgery, ablation, and imaging surveillance, respectively. Pathologic and survival outcomes and complications related to management were evaluated.
RESULTS. The malignancy rate at surgical pathology was 38% (3/8) for Bosniak IIF, 40% (29/72) for Bosniak III, and 90% (18/20) for Bosniak IV renal cysts. There were no metastases or deaths (0/144) directly related to Bosniak IIF renal cysts. There were no deaths (0/113) directly related to Bosniak III renal cysts, although one patient (1/113) developed local progression and lung metastases after thermal ablation. One patient with a Bosniak IV renal cyst (1/29) presented with and died of metastatic disease. Moderate to severe complications occurred in 19% (16/86), 5% (1/19), and 0% (0/181) of patients managed by surgery, ablation, and imaging surveillance, respectively (p < 0.0001). Severe complications occurred in 7% (6/86) of surgical patients and included multiorgan failure (n = 2), acute myocardial infarction (n = 1), acute ischemic stroke (n = 1), conversion to hemodialysis-dependent chronic kidney disease (n = 1), and postoperative severe hemorrhage (n = 1).
CONCLUSION. There were no deaths from Bosniak IIF or III renal cysts regardless of management approach. Moderate to severe complications are frequent in patients managed by surgery.
Keywords: Bosniak, cystic renal tumors, renal cysts
Renal cysts are common, are present in 50% of 50 year olds, and are often identified as incidental findings on cross-sectional radiologic imaging studies [1]. Only a very small portion of renal cysts are malignant at surgical pathology, representing approximately 5–10% of all primary renal malignancies. The most widely accepted method for differentiating benign from malignant renal cysts is the Bosniak classification system, which was developed in 1986 and uses cross-sectional radiologic imaging features to stratify renal cysts into various categories, each with a progressively increasing risk of malignancy at surgical pathology [1–3].
Most renal cysts are Bosniak category I or II and are benign and require no further clinical workup. The Bosniak IIF category, introduced in 1993, includes mildly complex renal cysts without measureable enhancement on multiphasic contrast-enhanced CT or MRI studies [1–4]. Bosniak IIF renal cysts are managed by imaging surveillance because they are typically benign [1–9]. A minority of Bosniak IIF renal cysts increase in complexity during imaging surveillance, a feature associated with a higher malignancy rate at surgical pathology [5–9].
Bosniak III and IV category renal cysts have measurable enhancement in thickened walls or septa on CT or MRI studies, and the presence of well-defined nodular soft-tissue components differentiates Bosniak IV from III renal cysts [1–3]. Slightly more than half of Bosniak III renal cysts and most Bosniak IV renal cysts are malignant at surgical pathology [1–3, 10, 11]. The standard of care for both Bosniak III and IV renal cysts is surgical excision, although imaging surveillance is an acceptable management strategy in patients with a short life expectancy or significant comorbidities [2, 3]. More recently, investigators are exploring the role of renal mass ablation for the management of Bosniak III and IV renal cysts [12–15].
The choice of surgery as the standard of care for the management of Bosniak III and IV renal cysts is primarily derived from historical guidelines and expert opinions that were based on malignancy rates at pathology after surgical resection [16]. There are currently no published studies reporting that surgical resection of Bosniak III or IV renal cysts prevents local invasion or metastatic disease or that surgery improves quality of life, survival, or mortality compared with other management strategies.
There is a paucity of information on survival outcomes and complications related to the various management strategies for Bosniak IIF, III, and IV renal cysts. Therefore, the objective of this multiinstitutional study was to evaluate the outcomes and complications related to the management of Bosniak IIF, III, and IV renal cysts.
| Materials and Methods |   |
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Informed consent was waived in this institutional review board–approved HIPAA-compliant multiinstitutional retrospective data registry study. The participating institutions were the University of Mississippi Medical Center, University of Alabama at Birmingham, and Wake Forest University Baptist Medical Center. Prospectively classified Bosniak IIF, III, and IV renal cysts in patients 18 years old or older were identified by a search of the radiology information system in reports from CT, MRI, or ultrasound imaging studies from each participating institution between January 2000 and October 2011 using the search term “Bosniak.” Subclassification of the cysts was performed manually because of the heterogeneity in the specific terms used to describe each category—for example, Bosniak 2F, Bosniak IIF, Bosniak-2F, Bosniak-IIF, Bosniak category 2F, Bosniak category IIF, and so on. Rereview of the images and reapplication of the Bosniak classification system were not performed because the intent of the study was to capture the patients’ outcomes, costs, and complications as they related to the initial classification, which heavily influences treatment decisions [10]. Patients with multiple cysts were categorized into groups on a per-patient basis using the highest Bosniak category renal cyst. The following patients were excluded: patients younger than 18 years old, patients who did not undergo surgery or ablation and had less than 1 year of imaging follow-up, and patients with von Hippel–Lindau syndrome.
A password-protected, encrypted, and secure Research Electronic Data Capture (REDCap) [17]. Web-based database containing 168 unique fields was constructed, and deidentified coded patient data derived from the electronic medical records was entered by investigators at each participating institution. In brief, the REDCap database captured patient demographics, imaging findings at diagnosis, preexisting comorbidities, information related to reclassifications, type and time of management (surgery, ablation, or imaging surveillance), duration of imaging and clinical surveillance, timing of clinically significant outcomes (pathology results, local invasion, metastases, death, and cause of death), and complications related to management. Patients who did not undergo surgery or ablation and who had at least one follow-up imaging study 1 year or more from the time of diagnosis were considered to be managed by imaging surveillance. The time and type of reclassification (upward or downward) of Bosniak IIF, III, and IV renal cysts were recorded if the reclassification event was permanent. A permanent reclassification event was defined as a change in classification that was consistent on all follow-up imaging reports or that led to a subsequent surgical or ablation procedure. Temporary reclassification events were not captured because these events may have resulted from differences in opinions or from differences in imaging techniques and because these events were refuted on subsequent imaging study reports. Preexisting comorbidities were coded according to the Charlson comorbidity index [18]. The severity of the complications directly related to management was graded from 1 to 4 using the Clavien classification system, whereby grades 1 and 2 were considered minor complications and grades 3 and 4 were considered major complications [19].
Patient demographics, comorbidities, management received, and outcomes were compared among Bosniak IIF, III, and IV groups and among management groups. Continuous variables are presented as median values (range) and are compared using the Kruskal-Wallis test. Categoric variables are presented as counts and proportions and are compared using the Fisher exact test. A univariate analysis to assess the association of management strategy and demographic variables with the incidence of complication was performed using the Fisher exact test.
A time-to-event analysis was performed to quantify the incidence of complications over time. One year after the initial classification, the date of surgery and the date of ablation were treated as time origins for patients managed by imaging surveillance, surgery, and ablation. The Gray's test was conducted to compare the cumulative incidences of complications among the management groups [20, 21].
| Results | |
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Patient characteristics and outcomes according to Bosniak category and management strategy are presented in Table 1. Based on the highest Bosniak category lesion, 286 patients with 312 Bosniak IIF, III, or IV renal cysts were placed into BIIF (n = 144), BIII (n = 113), and BIV (n = 29) groups, respectively. Most of the patients in the BIIF group (97%, 139/144) were managed by imaging surveillance. Conversely, most of the patients in the BIII and BIV groups were managed by surgery, although 35% (40/113) of patients in the BIII group were managed by imaging surveillance. All patients managed by ablation (n = 19) were treated using the percutaneous approach with imaging guidance.
Patients were significantly more likely to be managed by surgery or ablation than by imaging surveillance if the initial imaging study at the time of the diagnosis was ordered by a urologist (p < 0.001). The Charlson comorbidity index, sex, race, body mass index, smoking, history of nonmetastatic renal cell carcinoma (RCC), and history of a solid renal mass were not significantly associated with management strategy (p > 0.10 for each).
No patients in the study (0/286) developed locally advanced disease with invasion of an adjacent structure. There were no metastases or disease-specific deaths in the BIIF group (0/144). In the BIII group, one (1/113) patient with a history of a surgically resected solid papillary RCC developed local tumor progression and pulmonary metastatic disease after thermal ablation of a Bosniak III renal cyst that grew over an 8-year period of observation, triggering a change in management (see Table 1 footnote b for details). No other patients in the BIII group presented with or developed metastatic disease, and there were no disease-specific deaths (0/113) in the BIII group. In the BIV group, one patient (1/29) presented with widespread meta-static disease and a BIV renal cyst that was a highly necrotic papillary RCC at surgical pathology (see Table 1 footnote c for details). That same patient died of metastatic papillary RCC. No other patients in the BIV group presented with or developed metastatic disease, and there were no other deaths due to Bosniak IV renal cysts.
Eight Bosniak IIF, 72 Bosniak III, and 20 Bosniak IV renal cysts were surgically resected in 86 patients, and the pathologic findings are depicted in Figure 1. The malignancy rate of Bosniak III renal cysts was 40% (29/72), which is significantly lower than 90% (18/20) for surgically resected Bosniak IV renal cysts (p < 0.0001). The malignancy rate of Bosniak IIF renal cysts was 38% (3/8), which is not significantly different from the rate of malignancy of Bosniak III renal cysts (p = 1.000). The reasons for re-section of the Bosniak IIF renal cysts included an increase in size (n = 2), resected along with a Bosniak III or IV renal cyst (n = 2), resected during workup for renal transplant (n = 2), temporary reclassification as Bosniak III renal cyst based on ultrasound (n = 1), and unknown (n = 1). Surgically resected malignant Bosniak IIF, III, and IV renal cysts (n = 50) were Fuhrman grade 1 or 2 in 62% (31/50), grade 3 in 28% (14/50), grade 4 in 2% (1/50), and not reported in 8% (4/50) (Appendix 1).
 View larger version (78K) | Fig. 1 —Graph shows malignancy rates and pathologic subtypes of surgically resected Bosniak IIF, III, and IV renal cysts. Asterisk indicates that difference is statistically significant (p < 0.0001). RCC = renal cell carcinoma. |
The rates of permanent reclassification of Bosniak IIF, III, or IV renal cysts are shown in Table 2. Permanent upward or downward reclassification in the imaging surveillance cohort was uncommon (7%, 14/189). No Bosniak III renal cysts (0/40) in the imaging surveillance cohort were reclassified upward to Bosniak IV renal cysts or solid renal masses, although 2% (2/147) of Bosniak IIF renal cysts were permanently reclassified upward. Permanent downward reclassification occurred in 20% (8/40) of patients in the BIII group managed by imaging surveillance.
There were no deaths directly attributable to any of the management strategies. Moderate to severe complications occurred in 19% (16/86), 5% (1/19), and 0% (0/181) of patients managed by surgery, ablation, and imaging surveillance (p < 0.0001), respectively. The associations of treatment complication with management strategy and demographic variables are depicted in Table 3. Management strategy was the only variable associated with the rate of moderate to severe complications (p < 0.0001), and this association was driven by the greater number of surgical cases in higher Bosniak categories. Although there were an increased number of complications in those managed with open versus laparoscopic surgical technique, the difference was not statistically significant (Table 3). The time and type of complications by organ system and severity are depicted in Table 4. For patients managed with surgery, moderate to severe complications occurred during the procedure in 5% (4/86), inpatient but after the procedure in 7% (6/86), and outpatient after discharge in 7% (6/86). The cumulative incidences of complications related to each management strategy are depicted in Figure 2. Most complications (> 80%) occurred or were identified within 3 months from the time of surgery or ablation.
 View larger version (83K) | Fig. 2A —Cumulative incidence of complications by management strategy. A, Graphs show cumulative incidence of any complication (A) and of moderate to severe complications (B) by management strategy. Timing of complications is relative to time of diagnosis for patients managed by imaging surveillance and relative to time of ablation or surgery for other patients. Tic marks indicate time of censoring. |
 View larger version (77K) | Fig. 2B —Cumulative incidence of complications by management strategy. B, Graphs show cumulative incidence of any complication (A) and of moderate to severe complications (B) by management strategy. Timing of complications is relative to time of diagnosis for patients managed by imaging surveillance and relative to time of ablation or surgery for other patients. Tic marks indicate time of censoring. |
Severe complications (Clavien grade 4a) related to the management of Bosniak renal cysts occurred in 7% (6/86) of surgical cases and included multiorgan failure (n = 2), acute myocardial infarction (n = 1), conversion to hemodialysis-dependent chronic kidney disease (n = 1), acute ischemic stroke (n = 1), and severe postoperative hemorrhage (n = 1). There were no deaths (0/86) directly related to surgery for Bosniak renal cysts. A 70-year-old male patient had multiorgan failure (myocardial infarction with acute respiratory and renal failure) managed by cardiac catheterization, intubation, intensive care, and 48 days of inpatient hospital care after robot-assisted laparoscopic partial nephrectomy for a Bosniak III renal cyst that was benign at surgical pathology. A 62-year-old male patient had multiorgan failure (acute myocardial infarction and flash pulmonary edema) discovered several hours after laparoscopic partial nephrectomy for a Bosniak III renal cyst (papillary RCC at surgical pathology) that was managed by medical and intensive care and intubation. A 67-year-old male patient had an acute myocardial infarction during an open partial nephrectomy procedure for a Bosniak III renal cyst (papillary RCC at surgical pathology) that was managed medically. A 56-year-old female patient was placed on permanent hemodialysis because of significant worsening of chronic kidney disease after hospital discharge after laparoscopic partial nephrectomy for a Bosniak III renal cyst that was a cystic clear cell carcinoma at surgical pathology. A 55-year-old female patient had an ischemic stroke 7 weeks after laparoscopic nephrectomy for a Bosniak III renal cyst (papillary RCC at surgical pathology) that was managed conservatively. A 62-year-old male patient with a Bosniak III renal cyst (papillary RCC at surgical pathology) had symptomatic severe acute hemorrhage at the surgical site found within hours after open nephrectomy that was managed by vasopressors, multiple blood transfusions, and intensive care management.
| Discussion | |
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The most widely accepted method for identifying cystic renal neoplasms that are potentially malignant is by cross-sectional imaging and application of the Bosniak classification system. No other systematic approach or patient factors have been more strongly associated with malignancy at surgical pathology. The risk of malignancy in any individual Bosniak IIF, III, or IV renal cyst and the relative uncertainty of a significant downstream event, such as locally advanced disease, metastasis, or death, are the driving factors behind the current recommendations for management [2, 3]. However, the occurrence rate of these downstream significant events is underreported in the literature.
Because Bosniak IIF renal cysts are rarely malignant, the American College of Radiology (ACR) recommends imaging surveillance with CT or MRI without and with IV contrast material at 6 and 12 months after diagnosis and yearly thereafter for a total of 5 years [2, 3, 10, 22, 23]. The purpose of imaging surveillance is to identify Bosniak IIF renal cysts that progress to higher-category lesions because upward reclassification is associated with an increased malignancy rate [4–8, 22, 23]. The rate of permanent upward reclassification in our study was 5% (9/166), and others have reported rates of upward reclassification ranging from 5% to 16% and have reported upward reclassification as typically occurring in the first 2 years after diagnosis [4–8, 22, 23]. In the current multiinstitutional study and a study by Smith et al. [10], there were no reported cases of locally advanced disease, metastases, or deaths resulting from Bosniak IIF renal cysts with 1 year or more of imaging surveillance (n = 175 patients from four different medical centers). The absence of these clinically significant events suggests that conservative management of BIIF renal cysts is appropriate.
In our study, no Bosniak III or IV renal cysts became locally aggressive, and the malignancy rates for surgically resected Bosniak III and IV renal cysts were 40% (29/72) and 90% (18/20), respectively. A weighted average of our data and published rates of malignancy at surgical pathology suggest that 56% (252/451) of Bosniak III and 88% (229/261) of Bosniak IV renal cysts are malignant [8, 10]. In our study, one (1/113) patient with a history of RCC developed local tumor progression and metastatic disease after thermal ablation of a Bosniak III renal cyst that grew over an 8-year period of observation, triggering a change in management and thermal ablation of the cyst. Three years after subsequent thermal ablation and oligometastasectomy of the lung metastases, the patient was alive and had no apparent disease. This case is the only reported case of a Bosniak III renal cyst with distant metastases in an immunocompetent patient in the literature to date.
This solitary case of a Bosniak III renal cyst with distant metastatic disease suggests that a history of RCC may be an important risk factor to consider. In our study, 100% (4/4) of Bosniak III renal cysts that were surgically resected in patients with a history of RCC were malignant. A history of RCC was previously identified as a risk factor by a Cleveland Clinic team who reported that 100% (8/8) of Bosniak III renal cysts were malignant when this risk factor was present [10, 23]. This extraordinarily high rate of malignancy suggests that surgical resection of Bosniak III renal cysts should be strongly favored in patients with a history of RCC.
The current ACR recommendations for management of Bosniak III renal cysts is for surgical resection or imaging surveillance in patients with a short life expectancy or significant comorbidities [3]. On average, 44% of surgically resected Bosniak III renal cysts are benign, and there were no reported deaths in our study or in studies in the literature to date due to a Bosniak III renal cyst [8, 10]. In our study, moderate to severe complications occurred in 19% (16/86) of patients who underwent surgical resection of a Bosniak cyst. Furthermore, no patients (0/181) managed by imaging surveillance had any complications, 20% (8/40) of Bosniak III renal cysts managed by imaging surveillance were permanently reclassified downward, and the malignancy rate of Bosniak III renal cysts was less than half the malignancy rate of Bosniak IV renal cysts. These findings suggest that short-term imaging surveillance should be considered as an alternative primary management strategy for patients with Bosniak III renal cysts who do not have risk factors associated with malignancy (e.g., history of RCC, coexisting Bosniak IV renal cyst or solid renal malignancy, or a hereditary syndrome). A prospective clinical trial is needed to evaluate the safety of imaging surveillance as a primary management strategy for Bosniak III renal cysts.
Compared with Bosniak III renal cysts, Bosniak IV renal cysts are very likely malignant, and highly necrotic and aggressive solid renal neoplasms may present as Bosniak IV renal cysts on cross-sectional imaging [2, 3, 24]. There is limited experience with imaging surveillance of Bosniak IV renal lesions and no convincing data to suggest a change in management.
The role of ablation in the treatment of cystic renal neoplasms is unclear [12–15]. The frequency of complications and cost of ablation are less than surgery, but not all cystic renal lesions are amenable to ablation because of their size, location, or both. Further investigation is needed before this treatment strategy can be included in practice guidelines.
This study has several limitations. First, the study design is retrospective, and our evaluation of cystic renal lesions was limited to those that were prospectively described using the Bosniak classification system. Second, the overall sample size is small, and the durations of imaging and clinical follow-ups were short, thus limiting our ability to generalize the results to long-term benefits from any one particular management strategy. Third, the retrospective design and lack of a standardized follow-up interval or duration of follow-up limit evaluation of the natural course of Bosniak renal cysts because most Bosniak III and IV renal cysts are surgically resected.
In conclusion, short-term follow-up showed no locally advanced disease, metastases, or deaths resulting from Bosniak IIF renal cysts; most of these lesions were managed by imaging surveillance, and surgery was reserved primarily for cases showing a change in size, progression, or other circumstances. For Bosniak III renal cysts, nearly half of which are benign, we found that approximately 20% were permanently reclassified downward when initially managed by imaging surveillance, moderate to severe complications from surgery were frequent, metastatic disease was rare, and there were no deaths on short-term follow-up. The only reported metastasis from a Bosniak III renal cyst was in a patient with a history of RCC, a known risk factor for malignancy of a Bosniak III renal cyst. Last, Bosniak IV renal cysts are very likely to be malignant, and necrotic solid tumors can mask themselves as a Bosniak IV renal cyst. These results suggest that yearly imaging surveillance for Bosniak IIF renal cysts and surgical resection for Bosniak IV renal cysts are appropriate management strategies. The results also suggest that imaging surveillance should be investigated as a potential alternative management strategy in healthy patients with a Bosniak III renal cyst and no risk factors for malignancy (e.g., history of RCC or von Hippel–Lindau syndrome). Of course, a cost-effective analysis study and prospective trial with long-term follow-up are needed before changing the standard of care.
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