Curr Urol Rep (2014) 15:386 DOI 10.1007/s11934-013-0386-x

NEW IMAGING TECHNIQUES (A ATALA AND A RASTINEHAD, SECTION EDITORS)

The Role of Imaging in the Active Surveillance of Small Renal Masses P. G. K. Wagstaff & P. J. Zondervan & J. J. M. C. H. de la Rosette & M. P. Laguna

# Springer Science+Business Media New York 2014

Abstract Up to 66 % of renal cell carcinomas are detected as small renal masses before the presence of clinical symptoms. Small renal mass treatment has evolved from the exclusive use of radical nephrectomy to the use of nephron sparing procedures where possible. An increase in elderly and comorbid patients, together with the notion that just 20 % of small renal masses show high malignant potential, has prompted interest in active surveillance as a treatment option. Modern imaging techniques provide objective follow-up parameters, namely size, invasion of collecting system or perirenal fat and enhancement patterns, with minimal complication risks or patient discomfort. This review evaluates recent developments in the field of active surveillance for small renal masses. Special focus is placed on the role of imaging in the primary decision making and subsequent follow-up during active surveillance. Keywords Small renal mass . Renal cell carcinoma . Active surveillance . Therapy . Imaging . CT . MRI . Ultrasound . CEUS . PET Abbreviations ACT 11C-acetate AKI Acute kidney injury AML Angiomyolipoma AS Active surveillance AUA American Urological Association CEUS Contrast enhanced ultrasound CKD Chronic kidney disease This article is part of the Topical Collection on New Imaging Techniques P. G. K. Wagstaff : P. J. Zondervan : J. J. M. C. H. de la Rosette : M. P. Laguna (*) Department of Urology, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands e-mail: [email protected]

CT ccRCC EAU FDG HU MRI NSF PET RCC RFA SRM

Computed tomography Clear cell renal cell carcinoma European Association of Urology 18F-fluorodeoxyglucose Houndsfields units Magnetic resonance imaging Nephrogenic systemic fibrosis Positron emission tomography Renal cell carcinoma Radiofrequency ablation Small renal mass

Introduction A small renal mass (SRM) is defined as a solid, or partly solid, renal tumour with a maximal diameter ≤4 cm, contrast enhancing on CT or MRI imaging and, consequently, suspicious for RCC [1]. Up to 66 % of RCCs are detected as SRM before the presence of clinical symptoms such as flank pain and haematuria [1, 2]. With the possibility of early treatment, a decrease in the cancer related morbidity was expected; however, to date no reduced mortality by RCC has been reported. Mortality rates for localized tumours even show a 3 % annual increase, as presented by Sun et al., at the recent 2013 AUA meeting [3]. This implies that it is either still premature to objectivize the results of an early intervention, or some of these SRMs are of low malignant potential and most likely will not contribute to cancer specific mortality [4, 5]. The treatment of SRMs has shown a shift from radical nephrectomy to nephron sparing interventions. While technical advances in minimally invasive surgery and ablation have facilitated kidney preservation, the increase in life expectancy means that also a crude increase in the number of elderly

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patients suffering from multiple severe comorbidities and concomitant SRM is to be expected. In this patient group minimally invasive excisional or ablative techniques compete strongly with active surveillance (AS) policies [6•]. AS is especially suited for those SRMs of low malignant potential, in patients at risk for surgical intervention, and in those frail individuals where a poor complication tolerance is foreseen. Until now, the decision to pursue AS has been made primarily on the basis of age, comorbidity and gross imaging characteristics. However, these parameters and diagnostic methods lack the finesse to truly detect the malignant potential of an SRM. Renal mass biopsy, although highly accurate in determining histology in case of adequate sampling, is still hampered by a relatively high non-diagnostic rate in SRMs and seems to be prone to undergrading [7•, 8]. Ultimately although a combination of these diagnostic methods might offer a reasonable diagnostic accuracy, progression during AS can only be determined after a period of surveillance has been pursued [2]. This review aims to evaluate the most recent developments in the field of imaging in SRM, with focus on the role of imaging in the primary decision making and subsequent follow-up during AS.

Curr Urol Rep (2014) 15:386

comorbidity classification methods, such as the Charlson and Elixhauser comorbidity indices, have not been prospectively validated to predict the outcome of renal mass surgery [16]. A successful core biopsy or fine needle aspiration provides objective tumour differentiation with both sensitivity and specificity in the range of 95–100 % [17]. Therefore, biopsies are advised in all patients under AS [6•, 14]. However, a nondiagnostic rate of 10–20 % and even up to 30 %, is to be expected in SRMs [14, 17]. Fuhrman grade needs to be viewed with caution due to possible under-staging, concordance rates of biopsy and final pathology vary from 46 % to 94 % between studies [8]. With no clear guidance on how to assess morbidity together with the limitations of histopathological characterisation based on biopsy, decision making before and during AS relies mostly on imaging. Conversely, the definition of progression and follow-up of renal masses is also heavily dependent on imaging. Modern imaging techniques provide objective follow-up parameters, namely size, invasion of a collecting system or perirenal fat and enhancement patterns with minimal complication risks or patient discomfort.

The Role of Imaging in Primary Decision-Making Rationale for AS and Guidelines The rationale for AS is based on several facts. First, the majority of the SRMs seem to be of low malignant potential as stated before. Benign histology is found in 20 % of SRMs [9]. Out of the remaining 80 %, being RCC, a portion of only 20–25 % display aggressive histopathological characteristics making them potentially lethal [10, 11]. Secondly, in elderly patients with SRMs the mid-term risk of RCC related mortality is low compared to the risk of dying of non-cancer related causes. In patients aged ≥75 years significant predictors of survival were found to be age and comorbidity. The choice for surgical treatment does not improve overall survival [12]. This has led to belief that in elderly patients a period of AS poses a minor risk. Thirdly, a period of active surveillance does not jeopardize the possibility of still performing a NSS in most of the cases [13•]. The recently published AUA guideline on follow-up of clinically localized renal neoplasms describes AS as an option for all elderly patients after counselling on the possible risk of disease progression [14]. The EAU, in its 2010 guidelines on renal cell carcinoma, reserves AS for elderly and comorbid patients with small renal masses and limited life expectancy [6•]. However, the guidelines do not specify how to select patients on the basis of comorbidity and surgical risk, which are both difficult to quantify in an objective manner. The interpretation of the ASA classification, used widely for presurgical evaluation of physical status, varies greatly between different physicians and medical centres [15]. Furthermore,

The role of imaging in the primary decision-making is to determine the anatomical characteristics of the tumour including size, situation and relationship with sinus and the collecting system and the presence of gross lymph nodes but also the presence of distant metastasis. Tumour Size Estimation Tumour size at diagnosis is the easiest feature to assess by imaging and is an indicator of malignant potential. Most cohorts investigating the subject show a positive correlation between malignancy and tumour size at diagnosis. A benign percentage of 43–46 % is found in tumours

The role of imaging in the active surveillance of small renal masses.

Up to 66 % of renal cell carcinomas are detected as small renal masses before the presence of clinical symptoms. Small renal mass treatment has evolve...
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