EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 available at www.sciencedirect.com journal homepage: www.eu-openscience.europeanurology.com Review – Kidney Cancer Benefit and Harm of Active Surveillance for Biopsy-proven Renal Oncocytoma: A Systematic Review and Pooled Analysis Michael Baboudjian a,b,c,*, Daniel Moser d, Takafumi Yanagisawa d,e, Bastien Gondran-Tellier a, Eva M. Compérat f, Damien Ambrosetti g, Laurent Daniel h, Cyrille Bastide b, Shahrokh F. Shariat d, Eric Lechevallier a, Pietro Diana c, Alberto Breda c, Benjamin Pradere d, Romain Boissier a a Department of Urology and Kidney Transplantation, Aix-Marseille University, APHM, Conception University Hospital, Marseille, France; b Department of Urology, Aix-Marseille University, APHM, North University Hospital, Marseille, France; c Department of Urology, Fundació Puigvert, Autonoma University of Barcelona, Barcelona, Spain; d Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; e Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; f Department of Pathology, Medical University of Vienna, Vienna, Austria; g Department of Pathology, CHU Nice, University of Côte d’Azur, Nice, France; h Department of Pathology, Aix-Marseille University, APHM, La Timone University Hospital, Marseille, France Article info Abstract Article history: Context: Active surveillance (AS) of biopsy-proven renal oncocytomas may reduce Accepted April 30, 2022 overtreatment. However, on biopsy, the risk of misdiagnosis owing principally to entities with peculiar hybrids and overlap morphology, and phenotypes argues Associate Editor: for early intervention. M. Carmen Mir Objective: To assess the benefit and harm of AS in biopsy-proven renal oncocy- toma. Keywords: Evidence acquisition: A systematic review was conducted according to the Oncocytoma Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Renal Biopsy We systematically searched PubMed, Scopus, and Web of Science databases from Surveillance September 26 up to October 2021, for studies that analyzed the outcomes of AS Review in patients with biopsy-proven renal oncocytoma. Evidence synthesis: A total of ten studies with 633 patients met our inclusion cri- teria and were included for analysis. After a median follow-up of 34.5 mo (95% con- fidence interval [CI] 30.6–38.4), the overall definitive treatment rate from AS to definitive treatment was 17.3% (n = 75/433, six studies). The pooled pathological agreement between the initial renal mass biopsy and the surgical pathology report was 91.1%. The main indications for surgery during follow-up were rapid tumor growth and patient request. The pooled median growth rate was 1.55 mm/yr (95% CI 0.9–2.2). No metastasis or death related to renal oncocytoma was reported. Conclusions: Annual tumor growth of biopsy-proven renal oncocytoma is low. AS is oncologically safe, with favorable compliance of patients. Crossover to definitive * Corresponding author. Department of Urology and Kidney Transplantation, Aix-Marseille Univer- sity, APHM, Conception Academic Hospital, 147 boulevard Baille, 13005 Marseille, France. Tel. +33 625 314 029; Fax: +33 491 435 177. E-mail address: Michael.BABOUDJIAN@ap-hm.fr (M. Baboudjian). https://doi.org/10.1016/j.euros.2022.04.009 2666-1683/Ó 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 9 treatment revealed a strong concordance between biopsy and final pathology. Further studies on the long-term outcomes of AS are needed. Patient summary: In this study, we examined the benefit and harm of active surveillance (AS) in biopsy-proven oncocytoma. Based on the available data, AS appears oncologically safe and may represent a promising alternative to immediate treatment. Patients should be included in AS decision discussions. Ó 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/). 1. Introduction designs were included. The following keywords were used in our search strategy: (oncocytoma OR oncocytic) AND Renal oncocytomas are benign tumors that account for 3– (biopsy OR surveillance) AND (kidney OR renal). Initial 7% of all solid renal masses but represent up to 18% of small screening was performed independently by two investiga- renal masses (SRMs) [1]. The differentiation of renal onco- tors based on the titles and abstracts of articles to identify cytoma from renal cell carcinoma (RCC) such as chromo- ineligible reports. The reasons for exclusions were noted. phobe RCC is challenging, and imaging characteristics Potentially relevant reports were subjected to a full-text alone are unreliable [2]. For many years, the diagnosis of review, and the relevance of the reports was confirmed after renal oncocytomas was based on postoperative pathological the data extraction process. Disagreements were resolved analysis owing to the low rate of preoperative biopsy in the by consultation with a third coauthor. management of SRMs [3]. The incidental diagnosis of SRMs has increased in the 2.3. Inclusion and exclusion criteria past few decades [4] with a consequential increase in We included studies that analyzed patients with biopsy- benign tumor incidence, which has been reported in up to proven renal oncocytoma managed with AS. In case of 30.9% of the cases [5]. To avoid overtreatment of SRMs, duplicate publications, either the higher-quality or the most renal mass biopsies (RMBs) have gained interest in this set- recent publication was selected. Reviews, meta-analyses, ting [6]. There is growing evidence that RMBs have good letters, editorials, meeting abstracts, author replies, case accuracy for the diagnosis of SRMs [7] and that a routine reports, and non-English articles were excluded. No restric- RMB is associated with a reduction in unnecessary surgical tion on the publication date was applied. procedures for benign tumors [6]. In order to reduce the overtreatment of renal oncocy- 2.4. Data extraction and analysis tomas [3], active surveillance (AS) for biopsy-proven renal oncocytoma has been proposed. However, the lack of relia- Two review authors (M.B. and D.M.) performed an indepen- bility of RMBs to distinguish renal oncocytoma from other dent initial screening based on the titles and abstracts, and tumors included in the oncocytic neoplasm spectrum such noted the causes for exclusion of ineligible reports. Both as chromophobe RCC and the risk of missing other oncocytic authors independently extracted the following variables from tumors in an AS setting remain controversial [8]. To the included studies: first author’s name, publication year, improve decision-making for the management of renal country of research, study design, period of patient recruit- oncocytoma, we conducted a systematic review and pooled ment, number of patients included, baseline median tumor analysis of the benefit and harm of AS in biopsy-proven size (mm), median follow-up (mo), AS protocol, tumor growth renal oncocytoma. (mm/yr), conversion to definitive treatment (rate, indications, risk factors, and correlation between RMBs and surgical 2. Evidence acquisition pathology whether partial nephrectomy [PN] or radical nephrectomy was performed), complications and renal func- 2.1. Protocol and registration tion (between patients who remained under AS and those who underwent definitive treatment), metastasis-free survival, We conducted a systematic review in line with the Pre- and overall survival. All discrepancies regarding data extrac- ferred Reporting Items for Systematic Reviews and Meta- tion were resolved by consensus with a third coauthor (R.B.). analyses (PRISMA) guidelines [9]. A protocol was submitted to PROSPERO (registration number: CRD42021281340). 2.5. Risk of bias assessment The risk of bias (RoB) of the included studies was evaluated 2.2. Search strategy according to the ‘‘Risk Of Bias In Non-randomized Studies of A literature search was conducted up to October 2021 in Interventions (ROBINS-I)’’ tool [10]. ROBINS-I is the recom- PubMed/Medline, Scopus, and Web of Science databases. mended tool to be used in Cochrane Reviews for nonrandom- Studies were included if they comprised patients with ized studies of interventions. In addition, two reviewers biopsy-proven oncocytoma (patients) managed with AS (in- independently assessed the RoB using five confounding factors tervention) to assess the benefit and harm (outcomes). that were identified a priori: interval between two radiological There was no comparator in this study, and all study examinations, type of imaging on diagnosis and follow-up, 10 EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 reason for crossover from AS to definitive treatment, oncocy- identified. After duplicate removal, title and abstract toma differentiated from other oncocytic tumors, and annual screening, and full-text review, ten studies were included tumor growth. RoB summary and graph figures were generated for qualitative and quantitative analyses [12–21]. using the Cochrane Review Manager 5.4 (RevMan 5.4; The The baseline characteristics of the included studies are pre- Cochrane Centre, Copenhagen, Denmark). The overall RoB level sented in Table 1. All the studies included (n = 10) were retro- was judged as ‘‘low,’’ ‘‘unclear,’’ or ‘‘high’’ risk. spective. Of these, six were noncomparative studies, one reported a comparison between AS and PN, and three 2.6. Statistical analysis reported a comparison between oncocytoma and other RCCs. Sample sizes ranged from 15 to 98 cases including a total of Measures of interest included initial tumor size (mm), 633 patients, baseline tumor size varied from 15 to 34 mm, annual growth rate (measured in mm/yr), and duration of and median follow-up varied between 29 and 43 mo. follow-up (mo). The ‘‘metamedian’’ package in R (R Founda- tion for Statistical Computing, Vienna, Austria) was applied 3.2. RoB in the studies to estimate the pooled median, as described by McGrath et al [11]. The rates of metastasis and death from any cause RoB assessments are summarized in Fig. 2 (using ROBINS-I were extracted as numbers and proportions from the tool) and Fig. 3 (using the five confounding factors defined selected articles. All analyses were performed using R Ver- a priori). All studies were judged to have a moderate to high sion 4.0.2 (R Foundation for Statistical Computing). RoB using the ROBINS-I tool. Similarly, the RoB using the five confounding factors was found to be unclear or high for most domains assessed. 3. Evidence synthesis 3.3. Conversion from AS to definitive treatment 3.1. Study selection and characteristics Six studies including 433 patients reported the definitive The study selection process is outlined in the PRISMA flow treatment rates from AS to definitive treatment diagram (Fig. 1). A total of 2862 initial searches were [12–14,17–19]. In the pooled studies, the median Fig. 1 – PRISMA flow chart. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-analyses. EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 11 Table 1 – Overview of the main study characteristics that evaluated active surveillance in biopsy-proven renal oncocytoma Author Year Country of Study Study Number of Baseline median Median follow-up research design period patients included tumor size (mm) (mo) Neuzillet et al [17] 2005 France Retrospective 1998–2004 15 34 40.1 Kawaguchi et al [20] 2011 Canada Retrospective 2004–2010 29 26 40 Kurup et al [21] 2012 USA Retrospective 2000–2009 25 15 33 Richard et al [13] 2016 Canada Retrospective 2003–2014 79 NA 43 Liu et al [19] 2016 Australia Retrospective 2000–2014 53 30 34 Alderman et al [14] 2016 USA Retrospective 2006–2013 96 28 33 Miller et al [15] 2018 USA Retrospective 2003–2016 78 NA 39.8 Neves et al [18] 2021 UK Retrospective 2012–2019 98 34 29 Deledalle et al [12] 2021 France Retrospective 2010–2016 89 26 36 Meagher et al [16] 2021 USA/Italy Retrospective 2006–2018 71 26 35.3 NA = not available. follow-up was 34.5 mo (95% confidence interval [CI] 30.6– 2.7 mm/yr). Growth rate distribution was reported in 38.4). The proportion of patients undergoing a delayed four studies (265 patients and 276 tumors) [12,18,19,21]. intervention after an initial AS period ranged from 5% to Tumor size decreased in 38 cases (13.8%), a growth rate of 40%. An analysis of pooled data indicated an overall defini- <5 mm/yr was reported in 199 tumors (72.1%), and a tive treatment rate of 17.3% and a definitive treatment rate growth rate of >5 mm/yr was reported in 39 cases (14.1%). of 6% per year. Definitive treatments consisted of 35 abla- Three studies assessed the factors associated with tumor tive therapies and 40 surgeries. The types of ablative ther- growth [12,13,21]. Two studies failed to identify the predic- apy (radiofrequency or cryoablation) and surgery (PN or tive factors of growth [12,21], while Richard et al [13] found radical nephrectomy) used were not reported in all the that the initial tumor size was associated with tumor studies, preventing an accurate comparison of the fre- growth in a multivariate analysis. However, this analysis quency of definitive treatments used. was conducted in a cohort of patients with oncocytic neo- Indications for invasive treatment were reported in five plasm (oncocytoma and chromophobe RCC) [13]. studies [12,13,17–19] involving a total of 49/334 patients who underwent definitive treatment (surgical excision or 3.5. Renal function in patients under AS versus treated ablative treatment). When reported, indications for defini- patients tive treatment were rapid tumor growth (n = 32/49, 65%), patient request (n = 6/49, 13%), onset of symptoms Renal function was assessed in two studies [15,16]. Mea- (n = 5/49, 10%), change in tumor shape (n = 4/49, 8%), and gher et al [16] compared renal function outcomes in large tumor volume at baseline (>100 and 87 mm, patients under AS versus those who underwent PN. A total n = 2/49, 4%). of 295 patients were analyzed (224 PN/71 AS, median Three studies assessed the risk factors for crossover to follow-up 37.4 mo). The mean estimated glomerular filtra- definitive treatment [12,17,19]. Age on diagnosis was corre- tion rate (eGFR) at the last follow-up was lower in the AS lated with the likelihood of definitive treatment in every group (64.3 vs 70.5 ml/min/1.73 m2 in the PN group, study [12,17,19]. Other identified factors were a lower p = 0.03), with a higher rate of de novo eGFR of <60 ml/ Charlson comorbidity index (4 vs 2; p < 0.01), a higher min/1.73 m2 (28.2% vs 12.1%, p < 0.001). In a cohort of renal tumor growth rate during follow-up (3.8 vs 1.5 mm/yr; oncocytic neoplasms, Miller et al [15] compared the decline p < 0.001) [12], and a larger tumor size at baseline (50.0 in renal function at 1 and 3 yr of follow-up with baseline vs 27.3 mm, p = 0.02) [17]. renal function (%), according to the treatment used. Renal Five studies compared the pathological correlation function following treatment was lower for patients who between the initial renal mass biopsy and the final speci- underwent radical nephrectomy at 1 (78.5% glomerular fil- men [12,14,17–19]. Among the 34 patients included, 31 tration rate [GFR]) and 3 (77.4% GFR) yr versus PN (94.2% had a confirmed oncocytoma and two a hybrid tumor, and and 96.6%, respectively), ablation (90.0% and 94.2%, respec- in one case a low-grade RCC with oncocytic features could tively), and AS (99.6% and 95.9%, respectively; p < 0.01). not be excluded. Pooled data indicate that the concordance rate between the biopsy and the final specimen pathological 3.6. Complications in patients under AS versus treated examination was 91.1%. patients Meagher et al [16] compared complication rates in patients 3.4. Tumor growth under AS versus treated patients. The rate of complications The annual tumor growth rates were reported in seven observed in the PN group was higher (45/224, 20%) than studies, including 451 patients [12,13,15,18–21]. The that in the AS group (7/71, 9.9%), but the difference did pooled median initial tumor size was 25.8 mm (95% CI not reach statistical significance (p = 0.051). High-grade 17–34.6). The pooled median growth rate was 1.55 mm/yr complications were recorded only in the PN group (95% CI 0.9–2.2 mm/yr) with moderate heterogeneity (10/224, 4.5%). In the series of Deledalle et al [12], no com- between studies (median growth rates ranged from 1 to plications were reported in patients who remained under 12 EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 Overall survival was reported in two studies [13,18]. After a pooled median follow-up of 35.4 (range 21.7–49) mo in 177 patients, six deaths (3.4%) unrelated to renal oncocytoma occurred. 3.9. Discussion 3.9.1. Main findings and interpretation of the results In this systematic review and pooled analysis, we found that AS appeared to be a safe therapeutic option for biopsy-proven oncocytoma. With no oncocytoma-related deaths or distant metastases reported, and a pooled median growth rate of 1.55 mm/yr, AS is safe without missing the window of opportunity to perform surgery later during follow-up. Indeed, the pooled definitive treatment rate was only 17.3% among the studies. Nevertheless, our find- ings underline the lack of actual consensus regarding the criteria to decide for definitive treatment. In the present review, >85% of renal oncocytomas had slow or no growth. The overall growth rate observed in the pooled studies was 1.55 mm/yr, which is consistent with other reports dealing with AS of SRMs [22,23]. There are some data comparing growth rates between different pathological features, which suggest that growth rates for RCC and oncocytomas are not distinguishable [24,25]. How- ever, we found that tumor growth was often related to the indication for definitive treatment in patients with AS for biopsy-proven renal oncocytoma. Throughout the studies, fast tumor growth was the main indication for definitive treatment. The threshold for defin- ing rapid tumor growth was 5 mm/yr [17–19], but was unreported or subjective in some studies [12,13]. The indi- cation for definitive treatment based solely on tumor growth is questionable since oncocytomas appear to grow at the same rate as malignant tumors [22,26]. Moreover, Fig. 2 – Risk of bias assessment using the ROBINS-I tool. Low risk of bias is the pooled data indicate that the concordance rate between indicated by the color green, high risk of bias by red, and some concern by biopsy and final specimen was 91.1%, highlighting that a yellow. ROBINS = Risk Of Bias In Non-randomized Studies of Interventions. large number of definitive treatments in patients with rapid tumor growth could have been avoided. Nevertheless, Patel et al [8] reported a lower concordance with only 31 of 48 (64.6%) oncocytic neoplasms on RMBs to be oncocytomas AS, while three major complications were recorded on final specimen. The pathological similarity of renal onco- (three/24, 13%) in patients who had definitive treatment. cytoma to other oncocytic lesions is often debated as to whether a formal and definitive diagnosis of oncocytoma 3.7. AS Protocol (with typical features on the biopsy specimen) is preferable after biopsy or whether more general terminology, such as The AS protocol was described in five studies oncocytic neoplasm, should be used. [12,13,17,19,21]. Magnetic resonance imaging, ultrasound, The second most common reason for switching to defini- and computed tomography examinations were, respec- tive treatment was patient choice. While patient choice is a tively, used in three [12,13,21], four [12,13,17,19], and five crucial and well-studied issue in RCC [26,27], no data have [12,13,17,19,21] protocols. The frequency of radiological been reported in the management of renal oncocytoma. examinations varied between studies: every 3–6 mo [13], Treatment decisions are complex, especially for patients every 6–12 mo [17,19,21], or at least once a year [12]. with incidentally diagnosed oncocytoma. However, the pre- sent review showed that AS is oncologically safe. Patients should be aware that pathological examination of renal 3.8. Oncological outcomes tumor biopsy could miss other oncocytic renal neoplasms Five studies assessed metastasis-free survival, including in 9%, but deferred intervention is possible in case of atyp- 395 patients [12–15,19]. After a pooled median follow-up ical evolution. Therefore, no tumor-related deaths or distant of 35 (95% CI 31–39) mo, no metastasis was recorded. metastases were reported in the included studies. EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 13 Fig. 3 – Risk of bias assessment using five confounding factors defined a priori. Low risk of bias is indicated by the color green, high risk of bias by red, and some concern by yellow. 3.9.2. Limitations of the review and included studies Patel et al [8] showed in their meta-analysis of 205 biop- There are several limitations that should be acknowledged. sies of oncocytic renal masses that the positive predictive First, the available data on AS of biopsy-proven renal onco- value of the diagnosis of oncocytoma on biopsy was 67%. cytomas remain limited, with the inclusion of mainly non- However, when individual studies were considered, the comparative and retrospective studies. Although we confirmation rate on the final surgical specimen for the observed a pooled median follow-up of 34 mo, long-term diagnosis of oncocytoma varied widely, from 25% to 100% outcomes are still lacking, preventing clinicians from [8]. This great heterogeneity shows the important role of informing patients of the long-term safety of AS for interpretation by pathologists and resources implemented decision-making purposes. for tumor subtyping, such as immunohistochemistry and All the studies were published over a relatively long time genetic tools. A possible limitation is that during the early frame (1998–2019), during which the indications for an period of analysis, new oncocytic emerging entities such RMB may have varied considerably. Moreover, the inclusion as low-grade oncocytic tumors were not clearly defined in of patients in an AS protocol was left to the discretion of the literature. Nevertheless, these entities are rare and, as clinicians. opposed to chromophobe RCC, appear to share a favorable 14 EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 outcome with oncocytoma. In the present review, data Supervision: None. regarding pathologist experience and additional explo- Other: None. rations used were scarce. Therefore, well-designed large- scale trials with a centralized review of pathological slides Financial disclosures: Michael Baboudjian certifies that all conflicts of are required to confirm the findings of the present study. interest, including specific financial interests and relationships and affili- ations relevant to the subject matter or materials discussed in the manu- 3.9.3. Implications for practice and future research script (eg, employment/affiliation, grants or funding, consultancies, This review confirms that we can systematically propose AS honoraria, stock ownership or options, expert testimony, royalties, or to most of our patients with renal oncocytoma as a safe patents filed, received, or pending), are the following: None. therapeutic option. For the purposes of comparison between AS and immediate treatment, future investigations Funding/Support and role of the sponsor: None. should also provide medicoeconomic evaluation and patient-reported quality of life. Although a routine RMB has the potential to reduce sur- References gery for benign tumors, it has been shown that even centers that routinely perform RMBs still miss benign tumors that [1] Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The are operated [7]. The main risk factor reported for crossover 2016 WHO classification of tumours of the urinary system and male to definitive treatment was young age on diagnosis genital organs-part a: renal, penile, and testicular tumours. Eur Urol 2016;70:93–105. [12,17,19]. Definitive treatment for renal oncocytomas [2] Abdessater M, Kanbar A, Comperat E, et al. Renal oncocytoma: an may still be indicated in young patients with long life algorithm for diagnosis and management. Urology expectancies who do not wish to undergo life-long and 2020;143:173–80. stringent surveillance. In any case, surgery should be indi- [3] Neves JB, Withington J, Fowler S, et al. Contemporary surgical management of renal oncocytoma: a nation’s outcome. BJU Int cated before missing the window of opportunity to perform 2018;121:893–9. a PN in order to limit the risk of renal failure. [4] Kutikov A, Fossett LK, Ramchandani P, et al. Incidence of benign Defining standardized criteria for discontinuing AS of pathologic findings at partial nephrectomy for solitary renal mass presumed to be renal cell carcinoma on preoperative imaging. renal oncocytomas is mandatory. The threshold of 5 mm/ Urology 2006;68:737–40. yr to define a rapid growth rate and subsequently indicate [5] Kim JH, Li S, Khandwala Y, Chung KJ, Park HK, Chung BI. Association definitive treatment is based primarily on low-level evi- of prevalence of benign pathologic findings after partial dence [17]. A more relevant biological or radiological nephrectomy with preoperative imaging patterns in the United States from 2007 to 2014. JAMA Surg 2019;154:225–31. threshold could become the standard. [6] Marconi L, Dabestani S, Lam TB, et al. Systematic review and meta- Recently, increasing evidence has shown that analysis of diagnostic accuracy of percutaneous renal tumour technetium-99m (99mTc)-sestamibi [28,29] and radiomics biopsy. Eur Urol 2016;69:660–73. [30] are promising tools for differentiating renal oncocy- [7] Richard PO, Lavallée LT, Pouliot F, et al. Is routine renal tumor biopsy associated with lower rates of benign histology following tomas from clear cell RCCs. Before their clinical implemen- nephrectomy for small renal masses? J Urol 2018;200:731–6. tation, larger studies are necessary to better define the [8] Patel HD, Druskin SC, Rowe SP, Pierorazio PM, Gorin MA, Allaf ME. diagnostic accuracy of these images and their exact place Surgical histopathology for suspected oncocytoma on renal mass biopsy: a systematic review and meta-analysis. BJU Int in the AS protocol. 2017;119:661–6. [9] Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. 4. Conclusions BMJ 2021;372:n71. [10] Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. AS of biopsy-proven renal oncocytoma is a safe and feasible BMJ 2016;355:i4919. alternative to immediate treatment with a cumulative mid- [11] McGrath S, Zhao X, Qin ZZ, Steele R, Benedetti A. One-sample term definitive treatment rate of 17.3%. However, the aggregate data meta-analysis of medians. Stat Med included studies had high RoBs and long-term follow-up 2019;38:969–84. [12] Deledalle FX, Ambrosetti D, Durand M, et al. Active surveillance for data are lacking. To improve decision-making, patient pref- biopsy proven renal oncocytomas: outcomes and feasibility. erences and expectations must be taken into account. Urology 2021;156:185–90. [13] Richard PO, Jewett MA, Bhatt JR, Evans AJ, Timilsina N, Finelli A. Author contributions: Michael Baboudjian had full access to all the data Active surveillance for renal neoplasms with oncocytic features is safe. J Urol 2016;195:581–6. in the study and takes responsibility for the integrity of the data and the [14] Alderman MA, Daignault S, Wolf Jr JS, et al. Categorizing renal accuracy of the data analysis. oncocytic neoplasms on core needle biopsy: a morphologic and Study concept and design: Baboudjian, Pradere, Boissier. immunophenotypic study of 144 cases with clinical follow-up. Acquisition of data: Baboudjian, Moser, Yanagisawa. Hum Pathol 2016;55:1–10. [15] Miller BL, Mankowski Gettle L, Van Roo JR, et al. Comparative Analysis and interpretation of data: Baboudjian, Boissier, Gondran-Tellier, analysis of surgery, thermal ablation, and active surveillance for Pradere. renal oncocytic neoplasms. Urology 2018;112:92–7. Drafting of the manuscript: Baboudjian, Pradere, Boissier. [16] Meagher MF, Lane BR, Capitanio U, et al. Comparison of renal Critical revision of the manuscript for important intellectual content: Com- functional outcomes of active surveillance and partial nephrectomy pérat, Ambrosetti, Daniel, Bastide, Shariat, Lechevallier, Breda, Diana. in the management of oncocytoma. World J Urol 2021;39:1195–201. Statistical analysis: Baboudjian, Gondran-Tellier. [17] Neuzillet Y, Lechevallier E, Andre M, Daniel L, Nahon O, Coulange C. Obtaining funding: None. Follow-up of renal oncocytoma diagnosed by percutaneous tumor Administrative, technical, or material support: None. biopsy. Urology 2005;66:1181–5. EUROPEAN UROLOGY OPEN SCIENCE 41 (2022) 8–15 15 [18] Neves JB, Varley R, Agnesi S, et al. Growth and renal function [25] Chawla SN, Crispen PL, Hanlon AL, Greenberg RE, Chen DY, Uzzo RG. dynamics of renal oncocytomas in patients on active surveillance. The natural history of observed enhancing renal masses: meta- BJU Int 2021;128:722–7. analysis and review of the world literature. J Urol [19] Liu S, Lee S, Rashid P, et al. Active surveillance is suitable for 2006;175:425–31. intermediate term follow-up of renal oncocytoma diagnosed by [26] Campi R, Sessa F, Corti F, et al. Triggers for delayed intervention in percutaneous core biopsy. BJU Int 2016;118(Suppl 3):30–4. patients with small renal masses undergoing active surveillance: a [20] Kawaguchi S, Fernandes KA, Finelli A, Robinette M, Fleshner N, systematic review. Minerva Urol Nefrol 2020;72:389–407. Jewett MA. Most renal oncocytomas appear to grow: observations [27] Cheaib JG, Pierorazio PM. How does treatment uncertainty factor of tumor kinetics with active surveillance. J Urol into decisions to place patients on active surveillance for kidney 2011;186:1218–22. cancer? Eur Urol Focus 2019;5:946–8. [21] Kurup AN, Thompson RH, Leibovich BC, et al. Renal oncocytoma [28] Rowe SP, Gorin MA, Gordetsky J, et al. Initial experience using growth rates before intervention. BJU Int 2012;110:1444–8. 99mTc-MIBI SPECT/CT for the differentiation of oncocytoma from [22] Jewett MA, Mattar K, Basiuk J, et al. Active surveillance of small renal cell carcinoma. Clin Nucl Med 2015;40:309–13. renal masses: progression patterns of early stage kidney cancer. Eur [29] Gorin MA, Rowe SP, Baras AS, et al. Prospective evaluation of (99m) Urol 2011;60:39–44. Tc-sestamibi SPECT/CT for the diagnosis of renal oncocytomas and [23] Smaldone MC, Kutikov A, Egleston BL, et al. Small renal masses hybrid oncocytic/chromophobe tumors. Eur Urol 2016;69:413–6. progressing to metastases under active surveillance: a systematic [30] Li Y, Huang X, Xia Y, Long L. Value of radiomics in differential review and pooled analysis. Cancer 2012;118:997–1006. diagnosis of chromophobe renal cell carcinoma and renal [24] Uzosike AC, Patel HD, Alam R, et al. Growth kinetics of small renal oncocytoma. Abdom Radiol (NY) 2020;45:3193–201. masses on active surveillance: variability and results from the DISSRM Registry. J Urol 2018;199:641–8.