Original Study
Clinicopathologic Outcomes of Cystic Renal Cell Carcinoma Nicholas M. Donin,1 Sanjay Mohan,1 Hai Pham,1 Hersh Chandarana,2 Ankur Doshi,2 Fang-Ming Deng,3 Michael D. Stifelman,1 Samir S. Taneja,1 William C. Huang1 Abstract Patients commonly undergo nephrectomy for cystic renal masses because a predictable proportion of these masses contain malignant elements. We hypothesize that these cystic renal cell carcinomas (cRCCs) are less aggressive than stage-matched solid renal cell carcinomas (RCCs) and herein demonstrate a zero rate of recurrence in a cohort of 61 patients with moderate follow-up. Background: The purpose of this study was to describe the clinicopathologic characteristics and oncologic outcomes of patients who underwent nephrectomy for cystic renal masses. Patients and Methods: Using an institutional review board-approved database, we retrospectively reviewed the clinical, pathologic, radiologic, and oncologic outcome data of patients who received nephrectomy for a complex cystic renal mass. Results: Sixty-one patients were identified who received nephrectomy for a complex cystic lesion. Average age was 64 years. Thirty-nine (64%) patients were male. At the time of resection, 1 (1.6%), 3 (4.8%), 53 (86.8%), and 4 (6.5%) had a Bosniak category II, IIF, III, and IV cystic lesion, respectively. Nineteen (31.1%) patients were initially managed expectantly but underwent surgery because of progression of complexity on follow-up. Mean pathologic tumor size was 3.3 cm (range, 0.7-12 cm). Forty-eight (78.6%) of the lesions were found to be malignant. Thirty-seven (77.1%), 5 (10.4%), 4 (8.3%), and 2 (4.1%) were stage T1a, T1b, T2a, and T3a, respectively. Clear cell was the most common histologic subtype (44%), followed by papillary (21.3%), and unclassified RCC (4.9%). With a mean and median follow-up of 48.4 and 43.0 months, respectively, no patients developed a local or metastatic recurrence. All patients were alive at last follow-up. Conclusion: In our series with moderate follow-up, cystic RCCs do not appear to recur or progress regardless of size, histologic subtype, or grade. These findings suggest the malignant potential of cRCCs is significantly less than solid RCCs. Further investigation is required to determine if cRCCs should be classified and managed independently from solid RCCs. Clinical Genitourinary Cancer, Vol. 13, No. 1, 67-70 ª 2015 Elsevier Inc. All rights reserved. Keywords: Carcinoma, Cystic kidney disease, Neoplasm metastasis, Neoplasm staging, Nephrectomy, Renal cell
Introduction Complex cystic renal masses represent a diagnostic and management dilemma for clinicians. A substantial proportion of these cystic masses represent cystic renal cell carcinoma (cRCC), and are thought to represent a potential risk for the development of 1
Department of Urology Department of Radiology 3 Department of Pathology New York University School of Medicine, New York, NY 2
Submitted: Apr 9, 2014; Revised: Jun 21, 2014; Accepted: Jun 27, 2014; Epub: Jul 3, 2014 Address for correspondence: Nicholas M. Donin, MD, NYU Department of Urology, 150 East 32nd St, 2nd Floor, New York, NY 10016 Fax: 646-825-6329; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2014.06.018
advanced stage disease, metastasis, and death. Radiologic criteria have been established that can reliably predict the rate of malignant components within these masses, and these radiologic criteria are used to justify surgical excision of masses meeting radiologic criteria threshholds.1 However, the risk of metastases and death from cRCC has not been thoroughly characterized. These risks have been demonstrated for solid renal masses, and the current pathologic staging system of renal masses is used in part to predict its risk for recurrence, metastasis, and death.2 At present, the same system is used for cRCC, however, it is unclear whether the risk stratification provided by this staging schema is appropriate in cases of cRCC. Because staging is based at least in part on lesions size, and size in cRCC is often predominantly represented by its cystic fluid component and not its solid enhancing component, it might be that
Clinical Genitourinary Cancer February 2015
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Outcomes in Cystic Renal Cell Carcinoma the current staging system for cRCC overestimates its oncologic risk. We sought to shed light on this uncertainty by analyzing the clinicopathologic outcomes of a cohort of patients who underwent nephrectomy for a cystic renal mass, and compared those outcomes with historical data of patients who underwent nephrectomy for solid renal masses. We hypothesize that cRCC has a lower rate of recurrence and metastasis than solid renal cell carcinoma (RCC).
Patients and Methods Using an institutional review board-approved renal tumor database, we identified patients who underwent nephrectomy for a cystic renal mass suspicious for cRCC between October 2005 and March 2013 at a single institution. Procedures were performed by 1 of 3 surgeons. We retrospectively reviewed prospectively-collected clinical, pathologic, radiologic, surgical, and oncologic data of identified patients. All patients were received imaging with contrastenhanced computed tomography (CT), magnetic resonance, or both, except in cases for which renal insufficiency precluded the use of intravenous contrast agents. All radiologic studies were reviewed independently by genitourinary-trained radiologists to confirm a cystic lesion concerning for cRCC. Patients in whom there was > 20% solid enhancing component on preoperative imaging were excluded in an attempt to avoid inclusion of a previously solid renal mass that had undergone central cystic necrosis. Enhancement was defined as > 15 Hounsfield units on CT scans. The most recent Bosniak renal cyst classification criterion was used.3 All pathologic specimens were reviewed by a genitourinary-trained pathologist.
Results
68
-
Seventy patients were identified who received nephrectomy for a complex cystic lesion suspected to be cystic cRCC. Nine of these patients were eliminated after review of their preoperative radiographic studies, which demonstrated solid masses with central necrosis or > 20% solid tumor component. These patients were suspected of having a solid mass with extensive necrosis, rather than true cystic neoplasms. After eliminations, there were 61 patients available for analysis. Average age was 64 years. Forty (64%) patients were male. At the time of resection, 1 (1.6%), 3 (4.8%), 53 (86.8%), and 4 (6.5%) had a Bosniak category II, IIF, III, and IV cystic lesion respectively. Nineteen (31.1%) patients were initially managed expectantly but underwent surgery because of progression of complexity on followup imaging (Table 1). The mean tumor size was 3.3 cm (range, 0.7-12 cm) on final pathology. Forty-eight (78.6%) of the lesions were found to be malignant. Thirty-seven (77.1%), 5 (10.4%), 4 (8.3%), and 2 (4.1%) were stage T1a, T1b, T2a, and T3a, respectively. Nineteen (39.6%), 26 (54.1%), and 3 (6.3%) of the masses were found to be Fuhrman grade 1, 2, and 3, respectively. Clear cell was the most common histologic subtype (n ¼ 27, 44%), followed by papillary (n ¼ 13, 21.3%) and unclassified RCC (n ¼ 3, 4.9%) (Table 2). In our cohort, 42 (68.9%) cystic masses were removed surgically on diagnosis, and the remaining 19 (31.1%) were removed after demonstrating progression on imaging after a period of observation. More than 93% were removed via partial nephrectomy, with a relatively even distribution between open, laparoscopic, and robotic techniques (Table 3). Mean and median follow-up were 48.4 and 43.0 months (respectively). 41 (67%) of patients had at least 2 years of clinical
Clinical Genitourinary Cancer February 2015
Table 1 Clinical Characteristics of Patients Undergoing Nephrectomy for Cystic Renal Masses (n [ 61) Characteristic Age (Range), Years
Value 64.6 (23-92)
Sex Male Female Size at Diagnosis (cm)
39 (64%) 22 (35%) 3.7 (1-9.6)
Bosniak Category at Diagnosis II
1 (1.6%)
IIF
3 (4.8%)
III
53 (86.8%)
IV
4 (6.5%)
Number of Other Cystic Lesions 0
38 (61.3%)
1
11 (17.7%)
2
4 (6.5%)
>2
9 (14.5%)
Mean Follow-Up (Months)
48.4
Median Follow-Up (Months)
43.0
Minimum Follow-Up (Months) 6
58 (95.1%)
12
48 (78.7%)
18
43 (70.5%)
24
41 (67.2%)
36
35 (57.4%)
48
26 (42.6%)
60
21 (34.4%)
follow-up, and twenty-one (34%) patients had at least 5 years of clinical follow-up. No patients in the cohort developed a local or metastatic recurrence during their follow-up. All patients were alive at last follow-up.
Discussion Cystic renal masses are commonly resected because a certain proportion of these lesions contain malignant elements. The Bosniak classification system has consistently demonstrated the ability to predict, based on imaging findings, the proportion of these cystic masses that will be malignant. Centers specializing in the radiologic evaluation of such lesions have demonstrated an 82% rate of malignancy within Bosniak category III cysts.4 Despite a predictable rate of malignant cells present within these cysts, the disease-free survival after resection of these masses was 100% in our cohort. Other cohorts of patients with cRCC have been evaluated and show an identical 100% rate of recurrence-free and metastasis-free survival after surgical resection.5-7 In a single study a patient presented with metastatic disease and a second had aortocaval lymphadenopathy, but this study did not specifically include cystic masses with significant solid enhancing component, thus leaving open the possibility that these masses were not truly cRCC but rather solid lesions with cystic necrosis.6 The excellent outcomes reported herein and in the literature are better than would be expected for solid RCC of equivalent stage and grade. For example, using a nomogram
Nicholas M. Donin et al
Open
19 (31.1)
Laparoscopic
21 (34.4)
Robotic
21 (34.4)
RCC, and as such it might not be appropriate to stage and manage cRCC using the same system as solid RCC. Potential explanations for the favorable outcomes of cRCC are multiple. First, it must be recognized that because RCC staging is based in part on size, and because a substantial proportion of volume of these cystic lesions is represented by cyst fluid, rather than the solid enhancing soft-tissue components, it might be possible that size and thus stage overestimates the biologic aggressiveness in these lesions. Whether the volume of cyst fluid present in a cRCC is a surrogate for aggressiveness warrants further investigation. Some have cited the substantial proportion of these cysts that are low grade9-11 and in our series > 90% were Fuhrman grade 1 or 2. cRCCs also tend not to demonstrate histologic features of local invasiveness such as lymphovascular invasion, perinephric fat extension, and lymph node involvement, also suggesting a less aggressive underlying biology.10 A critical consideration is that similar to its solid counterpart, the cystic phenotype of RCC is not a single histopathologic entity, but rather represents a heterogenous group of distinct histologic subtypes.12 Some of these subtypes, such as multilocular cystic RCC, have an intrinsically cystic pattern of growth, and others such as papillary and clear-cell RCC are not intrinsically cystic neoplasms but can exhibit a cystic pattern of growth and might contain cysts as their dominant component.13 What is increasingly recognized is that certain histologic subtypes, multilocular cystic RCC for example, appear to have 100% cure rates with surgery,11,14-16 suggesting uniformly benign behavior. Because of the potential for nephron loss and subsequent renal insufficiency that can occur during treatment of renal lesions, it could be prudent to consider observation in these lesions when one might determine their histology identity preoperatively. Unfortunately, current imaging technology is unable to differentiate multiloculated cystic RCC from other benign or malignant cystic renal lesions.14 Another important consideration is that, as described by Hartman in his early description of cRCC, a proportion of cRCC will in fact be solid masses that have undergone extensive central cystic necrosis and, in our view, represent a distinct biological entity from masses that have an intrinsically cystic pattern of growth, or which originate from the lining of a cyst.9,17,18 We agree that these neoplasms with central cystic necrosis represent a biologically distinct entity from both the subtypes with an intrinsically cystic pattern of growth, and the subtypes. As such, we chose to exclude these masses from our analysis. Our study has several mentionable limitations. Definitive conclusions regarding cancer-specific survival are limited based on our cohort size and median follow-up of 43 months. However, when considered alongside the multiple cohorts from other institutions that also demonstrate an exceedingly low rate of metastasis and recurrence after treatment of cRCC, all available evidence suggests that when compared stage-for-stage, cRCC is a significantly lowerrisk lesion than its solid counterpart. Our results represent outcomes from a tertiary-care, high-volume referral center and thus might not be applicable to other centers or surgeons performing fewer procedures.
Partial
57 (93.5)
Conclusion
Radical
4 (6.5)
Table 2 Pathologic Outcomes of Patients Undergoing Nephrectomy for Cystic Renal Masses Variable Pathologic Size (Range), cm
Value 3.3 (0.7-12)
Pathologic Stage T1a
37 (77.1)
T1b
5 (10.4)
T2a
4 (8.3)
T3a
2 (4.1)
Grade 1
19 (39.6)
2
26 (54.1)
3
3 (6.3)
Pathologic Subtype Clear cell
27 (44.3)
Papillary
13 (21.3)
Benign cyst
10 (16.4)
Unclassified RCC
3 (4.9)
Multilocular cystic RCC
2 (3.2)
Mixed epithelial stromal
2 (3.2)
Chromophobe
1 (1.6)
Juxtaglomerular
1 (1.6)
Oncocytic
1 (1.6)
Tubulocystic
1 (1.6)
Recurrences
0 (0)
Deaths From Cystic RCC
0 (0)
Data are presented as n (%) except where otherwise noted. Abbreviation: RCC ¼ renal cell carcinoma.
for the prediction of 5-year freedom for recurrence in solid clear-cell solid RCC, the 5-year disease-free survival for a 5-cm, stage pT2a lesion is approximately 90%.8 Although our cohort was far too small to demonstrate a significant difference in 5-year freedom from survival and our follow-up too short to draw definitive conclusions, our data and the data of others suggest that patients with cRCC might have superior oncologic outcomes than stage-matched solid RCC counterparts. Stated more simply, stage-for-stage, cRCC appears to have more favorable outcomes after nephrectomy than solid
Table 3 Surgical Characteristics of Nephrectomy for Cystic Renal Masses Characteristic
n (%)
Nephrectomy Immediate
42 (68.9)
Performed after progression
19 (31.1)
Approach
Radical Versus Partial
In this retrospective single-institution cohort study, we evaluated the clinical outcomes of 61 patients who underwent partial or
Clinical Genitourinary Cancer February 2015
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Outcomes in Cystic Renal Cell Carcinoma radical nephrectomy for lesions suspected to be cRCC. During a median of 43 months of follow-up no patients experienced a recurrence or died of disease. These outcomes are superior to that which would be expected in stage- and grade-matched solid RCC, suggesting that the staging system used in solid RCC might overestimate the risk represented by cRCC. A separate staging system should be considered in light of the superior outcomes in treated cRCC.
Clinical Practice Points Complex renal cysts are commonly identified on imaging studies
for unrelated conditions. Radiologic criteria (Bosniak classification) have been established
that reliably predict the risk of malignant elements within these masses. Concern regarding the development of metastatic disease and death prompts surgical resection of these masses. The malignant potential of these masses, however, has not been clearly demonstrated. In our study of 61 patients who underwent nephrectomy for a cystic mass concerning for cRCC, 48 patients (79%) were found to have malignant cRCC, and after a mean follow-up of 48 months, none developed metastatic disease, which is less than would be expected in a stage- and grade-matched cohort of solid RCC. At present, solid RCC and cRCC are staged using the same staging system, of which size is a significant component. Because these cystic masses appear to have better outcomes than their solid counterpart after nephrectomy, it might be that the current staging system overstates the risk of cRCC. A separate staging system for cRCC should be considered in light of the superior outcomes in treated cRCC.
Disclosure Michael D. Stifelman has been a paid consultant for VTI and Surgiquest and a paid lecturer for Intuitive. No direct financial conflict of interest is identified. Samir S. Taneja is a consultant for
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Clinical Genitourinary Cancer February 2015
GTX, Healthtronics, and Bayer, speaker for Janssen, and has royalties from Elsevier. No direct financial conflict of interest is identified. William C. Huang is a consultant for Janssen, The Medicines Company, and Ethicon. No direct financial conflict of interest is identified. The remaining authors have stated that they have no conflicts of interest.
References 1. Bosniak MA. The current radiological approach to renal cysts. Radiology 1986; 158:1-10. 2. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010. 3. Bosniak MA. The Bosniak renal cyst classification: 25 years later. Radiology 2012; 262:781-5. 4. O’Malley RL, Godoy G, Hecht EM, et al. Bosniak category IIF designation and surgery for complex renal cysts. J Urol 2009; 182:1091-5. 5. El-Mokadem I, Budak M, Pillai S, et al. Progression, interobserver agreement, and malignancy rate in complex renal cysts (Bosniak category IIF). Urol Oncol 2014; 32:24.e21. 6. Jhaveri K, Gupta P, Elmi A, et al. Cystic renal cell carcinomas: do they grow, metastasize, or recur? AJR Am J Roentgenol 2013; 201:W292-6. 7. Webster WS, Thompson RH, Cheville JC, et al. Surgical resection provides excellent outcomes for patients with cystic clear cell renal cell carcinoma. Urology 2007; 70:900-4. 8. Sorbellini M, Kattan MW, Snyder ME, et al. A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol 2005; 173:48-51. 9. Han KR, Janzen NK, McWhorter VC, et al. Cystic renal cell carcinoma: biology and clinical behavior. Urol Oncol 2004; 22:410-4. 10. Onishi T, Oishi Y, Goto H, et al. Cyst-associated renal cell carcinoma: clinicopathologic characteristics and evaluation of prognosis in 27 cases. Int J Urol 2001; 8:268-74. 11. Suzigan S, Lopez-Beltran A, Montironi R, et al. Multilocular cystic renal cell carcinoma: a report of 45 cases of a kidney tumor of low malignant potential. Am J Clin Pathol 2006; 125:217-22. 12. Deng FM, Melamed J. Histologic variants of renal cell carcinoma: does tumor type influence outcome? Urol Clin North Am 2012; 39:119-32. 13. Moch H. Cystic renal tumors: new entities and novel concepts. Adv Anat Pathol 2010; 17:209-14. 14. Hindman NM, Bosniak MA, Rosenkrantz AB, et al. Multilocular cystic renal cell carcinoma: comparison of imaging and pathologic findings. AJR Am J Roentgenol 2012; 198:W20-6. 15. Nassir A, Jollimore J, Gupta R, et al. Multilocular cystic renal cell carcinoma: a series of 12 cases and review of the literature. Urology 2002; 60:421-7. 16. Koga S, Nishikido M, Hayashi T, et al. Outcome of surgery in cystic renal cell carcinoma. Urology 2000; 56:67-70. 17. Hamid Y, Poller DN. Spontaneous regression of renal cell carcinoma: a pitfall in diagnosis of renal lesions. J Clin Pathol 1998; 51:334-6. 18. Hartman DS, Davis CJ Jr, Johns T, et al. Cystic renal cell carcinoma. Urology 1986; 28:145-53.
Clinicopathologic Outcomes of Cystic Renal Cell Carcinoma Nicholas M. Donin,1 Sanjay Mohan,1 Hai Pham,1 Hersh Chandarana,2 Ankur Doshi,2 Fang-Ming Deng,3 Michael D. Stifelman,1 Samir S. Taneja,1 William C. Huang1 Abstract Patients commonly undergo nephrectomy for cystic renal masses because a predictable proportion of these masses contain malignant elements. We hypothesize that these cystic renal cell carcinomas (cRCCs) are less aggressive than stage-matched solid renal cell carcinomas (RCCs) and herein demonstrate a zero rate of recurrence in a cohort of 61 patients with moderate follow-up. Background: The purpose of this study was to describe the clinicopathologic characteristics and oncologic outcomes of patients who underwent nephrectomy for cystic renal masses. Patients and Methods: Using an institutional review board-approved database, we retrospectively reviewed the clinical, pathologic, radiologic, and oncologic outcome data of patients who received nephrectomy for a complex cystic renal mass. Results: Sixty-one patients were identified who received nephrectomy for a complex cystic lesion. Average age was 64 years. Thirty-nine (64%) patients were male. At the time of resection, 1 (1.6%), 3 (4.8%), 53 (86.8%), and 4 (6.5%) had a Bosniak category II, IIF, III, and IV cystic lesion, respectively. Nineteen (31.1%) patients were initially managed expectantly but underwent surgery because of progression of complexity on follow-up. Mean pathologic tumor size was 3.3 cm (range, 0.7-12 cm). Forty-eight (78.6%) of the lesions were found to be malignant. Thirty-seven (77.1%), 5 (10.4%), 4 (8.3%), and 2 (4.1%) were stage T1a, T1b, T2a, and T3a, respectively. Clear cell was the most common histologic subtype (44%), followed by papillary (21.3%), and unclassified RCC (4.9%). With a mean and median follow-up of 48.4 and 43.0 months, respectively, no patients developed a local or metastatic recurrence. All patients were alive at last follow-up. Conclusion: In our series with moderate follow-up, cystic RCCs do not appear to recur or progress regardless of size, histologic subtype, or grade. These findings suggest the malignant potential of cRCCs is significantly less than solid RCCs. Further investigation is required to determine if cRCCs should be classified and managed independently from solid RCCs. Clinical Genitourinary Cancer, Vol. 13, No. 1, 67-70 ª 2015 Elsevier Inc. All rights reserved. Keywords: Carcinoma, Cystic kidney disease, Neoplasm metastasis, Neoplasm staging, Nephrectomy, Renal cell
Introduction Complex cystic renal masses represent a diagnostic and management dilemma for clinicians. A substantial proportion of these cystic masses represent cystic renal cell carcinoma (cRCC), and are thought to represent a potential risk for the development of 1
Department of Urology Department of Radiology 3 Department of Pathology New York University School of Medicine, New York, NY 2
Submitted: Apr 9, 2014; Revised: Jun 21, 2014; Accepted: Jun 27, 2014; Epub: Jul 3, 2014 Address for correspondence: Nicholas M. Donin, MD, NYU Department of Urology, 150 East 32nd St, 2nd Floor, New York, NY 10016 Fax: 646-825-6329; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2014.06.018
advanced stage disease, metastasis, and death. Radiologic criteria have been established that can reliably predict the rate of malignant components within these masses, and these radiologic criteria are used to justify surgical excision of masses meeting radiologic criteria threshholds.1 However, the risk of metastases and death from cRCC has not been thoroughly characterized. These risks have been demonstrated for solid renal masses, and the current pathologic staging system of renal masses is used in part to predict its risk for recurrence, metastasis, and death.2 At present, the same system is used for cRCC, however, it is unclear whether the risk stratification provided by this staging schema is appropriate in cases of cRCC. Because staging is based at least in part on lesions size, and size in cRCC is often predominantly represented by its cystic fluid component and not its solid enhancing component, it might be that
Clinical Genitourinary Cancer February 2015
- 67
Outcomes in Cystic Renal Cell Carcinoma the current staging system for cRCC overestimates its oncologic risk. We sought to shed light on this uncertainty by analyzing the clinicopathologic outcomes of a cohort of patients who underwent nephrectomy for a cystic renal mass, and compared those outcomes with historical data of patients who underwent nephrectomy for solid renal masses. We hypothesize that cRCC has a lower rate of recurrence and metastasis than solid renal cell carcinoma (RCC).
Patients and Methods Using an institutional review board-approved renal tumor database, we identified patients who underwent nephrectomy for a cystic renal mass suspicious for cRCC between October 2005 and March 2013 at a single institution. Procedures were performed by 1 of 3 surgeons. We retrospectively reviewed prospectively-collected clinical, pathologic, radiologic, surgical, and oncologic data of identified patients. All patients were received imaging with contrastenhanced computed tomography (CT), magnetic resonance, or both, except in cases for which renal insufficiency precluded the use of intravenous contrast agents. All radiologic studies were reviewed independently by genitourinary-trained radiologists to confirm a cystic lesion concerning for cRCC. Patients in whom there was > 20% solid enhancing component on preoperative imaging were excluded in an attempt to avoid inclusion of a previously solid renal mass that had undergone central cystic necrosis. Enhancement was defined as > 15 Hounsfield units on CT scans. The most recent Bosniak renal cyst classification criterion was used.3 All pathologic specimens were reviewed by a genitourinary-trained pathologist.
Results
68
-
Seventy patients were identified who received nephrectomy for a complex cystic lesion suspected to be cystic cRCC. Nine of these patients were eliminated after review of their preoperative radiographic studies, which demonstrated solid masses with central necrosis or > 20% solid tumor component. These patients were suspected of having a solid mass with extensive necrosis, rather than true cystic neoplasms. After eliminations, there were 61 patients available for analysis. Average age was 64 years. Forty (64%) patients were male. At the time of resection, 1 (1.6%), 3 (4.8%), 53 (86.8%), and 4 (6.5%) had a Bosniak category II, IIF, III, and IV cystic lesion respectively. Nineteen (31.1%) patients were initially managed expectantly but underwent surgery because of progression of complexity on followup imaging (Table 1). The mean tumor size was 3.3 cm (range, 0.7-12 cm) on final pathology. Forty-eight (78.6%) of the lesions were found to be malignant. Thirty-seven (77.1%), 5 (10.4%), 4 (8.3%), and 2 (4.1%) were stage T1a, T1b, T2a, and T3a, respectively. Nineteen (39.6%), 26 (54.1%), and 3 (6.3%) of the masses were found to be Fuhrman grade 1, 2, and 3, respectively. Clear cell was the most common histologic subtype (n ¼ 27, 44%), followed by papillary (n ¼ 13, 21.3%) and unclassified RCC (n ¼ 3, 4.9%) (Table 2). In our cohort, 42 (68.9%) cystic masses were removed surgically on diagnosis, and the remaining 19 (31.1%) were removed after demonstrating progression on imaging after a period of observation. More than 93% were removed via partial nephrectomy, with a relatively even distribution between open, laparoscopic, and robotic techniques (Table 3). Mean and median follow-up were 48.4 and 43.0 months (respectively). 41 (67%) of patients had at least 2 years of clinical
Clinical Genitourinary Cancer February 2015
Table 1 Clinical Characteristics of Patients Undergoing Nephrectomy for Cystic Renal Masses (n [ 61) Characteristic Age (Range), Years
Value 64.6 (23-92)
Sex Male Female Size at Diagnosis (cm)
39 (64%) 22 (35%) 3.7 (1-9.6)
Bosniak Category at Diagnosis II
1 (1.6%)
IIF
3 (4.8%)
III
53 (86.8%)
IV
4 (6.5%)
Number of Other Cystic Lesions 0
38 (61.3%)
1
11 (17.7%)
2
4 (6.5%)
>2
9 (14.5%)
Mean Follow-Up (Months)
48.4
Median Follow-Up (Months)
43.0
Minimum Follow-Up (Months) 6
58 (95.1%)
12
48 (78.7%)
18
43 (70.5%)
24
41 (67.2%)
36
35 (57.4%)
48
26 (42.6%)
60
21 (34.4%)
follow-up, and twenty-one (34%) patients had at least 5 years of clinical follow-up. No patients in the cohort developed a local or metastatic recurrence during their follow-up. All patients were alive at last follow-up.
Discussion Cystic renal masses are commonly resected because a certain proportion of these lesions contain malignant elements. The Bosniak classification system has consistently demonstrated the ability to predict, based on imaging findings, the proportion of these cystic masses that will be malignant. Centers specializing in the radiologic evaluation of such lesions have demonstrated an 82% rate of malignancy within Bosniak category III cysts.4 Despite a predictable rate of malignant cells present within these cysts, the disease-free survival after resection of these masses was 100% in our cohort. Other cohorts of patients with cRCC have been evaluated and show an identical 100% rate of recurrence-free and metastasis-free survival after surgical resection.5-7 In a single study a patient presented with metastatic disease and a second had aortocaval lymphadenopathy, but this study did not specifically include cystic masses with significant solid enhancing component, thus leaving open the possibility that these masses were not truly cRCC but rather solid lesions with cystic necrosis.6 The excellent outcomes reported herein and in the literature are better than would be expected for solid RCC of equivalent stage and grade. For example, using a nomogram
Nicholas M. Donin et al
Open
19 (31.1)
Laparoscopic
21 (34.4)
Robotic
21 (34.4)
RCC, and as such it might not be appropriate to stage and manage cRCC using the same system as solid RCC. Potential explanations for the favorable outcomes of cRCC are multiple. First, it must be recognized that because RCC staging is based in part on size, and because a substantial proportion of volume of these cystic lesions is represented by cyst fluid, rather than the solid enhancing soft-tissue components, it might be possible that size and thus stage overestimates the biologic aggressiveness in these lesions. Whether the volume of cyst fluid present in a cRCC is a surrogate for aggressiveness warrants further investigation. Some have cited the substantial proportion of these cysts that are low grade9-11 and in our series > 90% were Fuhrman grade 1 or 2. cRCCs also tend not to demonstrate histologic features of local invasiveness such as lymphovascular invasion, perinephric fat extension, and lymph node involvement, also suggesting a less aggressive underlying biology.10 A critical consideration is that similar to its solid counterpart, the cystic phenotype of RCC is not a single histopathologic entity, but rather represents a heterogenous group of distinct histologic subtypes.12 Some of these subtypes, such as multilocular cystic RCC, have an intrinsically cystic pattern of growth, and others such as papillary and clear-cell RCC are not intrinsically cystic neoplasms but can exhibit a cystic pattern of growth and might contain cysts as their dominant component.13 What is increasingly recognized is that certain histologic subtypes, multilocular cystic RCC for example, appear to have 100% cure rates with surgery,11,14-16 suggesting uniformly benign behavior. Because of the potential for nephron loss and subsequent renal insufficiency that can occur during treatment of renal lesions, it could be prudent to consider observation in these lesions when one might determine their histology identity preoperatively. Unfortunately, current imaging technology is unable to differentiate multiloculated cystic RCC from other benign or malignant cystic renal lesions.14 Another important consideration is that, as described by Hartman in his early description of cRCC, a proportion of cRCC will in fact be solid masses that have undergone extensive central cystic necrosis and, in our view, represent a distinct biological entity from masses that have an intrinsically cystic pattern of growth, or which originate from the lining of a cyst.9,17,18 We agree that these neoplasms with central cystic necrosis represent a biologically distinct entity from both the subtypes with an intrinsically cystic pattern of growth, and the subtypes. As such, we chose to exclude these masses from our analysis. Our study has several mentionable limitations. Definitive conclusions regarding cancer-specific survival are limited based on our cohort size and median follow-up of 43 months. However, when considered alongside the multiple cohorts from other institutions that also demonstrate an exceedingly low rate of metastasis and recurrence after treatment of cRCC, all available evidence suggests that when compared stage-for-stage, cRCC is a significantly lowerrisk lesion than its solid counterpart. Our results represent outcomes from a tertiary-care, high-volume referral center and thus might not be applicable to other centers or surgeons performing fewer procedures.
Partial
57 (93.5)
Conclusion
Radical
4 (6.5)
Table 2 Pathologic Outcomes of Patients Undergoing Nephrectomy for Cystic Renal Masses Variable Pathologic Size (Range), cm
Value 3.3 (0.7-12)
Pathologic Stage T1a
37 (77.1)
T1b
5 (10.4)
T2a
4 (8.3)
T3a
2 (4.1)
Grade 1
19 (39.6)
2
26 (54.1)
3
3 (6.3)
Pathologic Subtype Clear cell
27 (44.3)
Papillary
13 (21.3)
Benign cyst
10 (16.4)
Unclassified RCC
3 (4.9)
Multilocular cystic RCC
2 (3.2)
Mixed epithelial stromal
2 (3.2)
Chromophobe
1 (1.6)
Juxtaglomerular
1 (1.6)
Oncocytic
1 (1.6)
Tubulocystic
1 (1.6)
Recurrences
0 (0)
Deaths From Cystic RCC
0 (0)
Data are presented as n (%) except where otherwise noted. Abbreviation: RCC ¼ renal cell carcinoma.
for the prediction of 5-year freedom for recurrence in solid clear-cell solid RCC, the 5-year disease-free survival for a 5-cm, stage pT2a lesion is approximately 90%.8 Although our cohort was far too small to demonstrate a significant difference in 5-year freedom from survival and our follow-up too short to draw definitive conclusions, our data and the data of others suggest that patients with cRCC might have superior oncologic outcomes than stage-matched solid RCC counterparts. Stated more simply, stage-for-stage, cRCC appears to have more favorable outcomes after nephrectomy than solid
Table 3 Surgical Characteristics of Nephrectomy for Cystic Renal Masses Characteristic
n (%)
Nephrectomy Immediate
42 (68.9)
Performed after progression
19 (31.1)
Approach
Radical Versus Partial
In this retrospective single-institution cohort study, we evaluated the clinical outcomes of 61 patients who underwent partial or
Clinical Genitourinary Cancer February 2015
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Outcomes in Cystic Renal Cell Carcinoma radical nephrectomy for lesions suspected to be cRCC. During a median of 43 months of follow-up no patients experienced a recurrence or died of disease. These outcomes are superior to that which would be expected in stage- and grade-matched solid RCC, suggesting that the staging system used in solid RCC might overestimate the risk represented by cRCC. A separate staging system should be considered in light of the superior outcomes in treated cRCC.
Clinical Practice Points Complex renal cysts are commonly identified on imaging studies
for unrelated conditions. Radiologic criteria (Bosniak classification) have been established
that reliably predict the risk of malignant elements within these masses. Concern regarding the development of metastatic disease and death prompts surgical resection of these masses. The malignant potential of these masses, however, has not been clearly demonstrated. In our study of 61 patients who underwent nephrectomy for a cystic mass concerning for cRCC, 48 patients (79%) were found to have malignant cRCC, and after a mean follow-up of 48 months, none developed metastatic disease, which is less than would be expected in a stage- and grade-matched cohort of solid RCC. At present, solid RCC and cRCC are staged using the same staging system, of which size is a significant component. Because these cystic masses appear to have better outcomes than their solid counterpart after nephrectomy, it might be that the current staging system overstates the risk of cRCC. A separate staging system for cRCC should be considered in light of the superior outcomes in treated cRCC.
Disclosure Michael D. Stifelman has been a paid consultant for VTI and Surgiquest and a paid lecturer for Intuitive. No direct financial conflict of interest is identified. Samir S. Taneja is a consultant for
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GTX, Healthtronics, and Bayer, speaker for Janssen, and has royalties from Elsevier. No direct financial conflict of interest is identified. William C. Huang is a consultant for Janssen, The Medicines Company, and Ethicon. No direct financial conflict of interest is identified. The remaining authors have stated that they have no conflicts of interest.
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