








































This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2022 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

Key Words Competing Interests Article Information

Small renal mass, active surveillance, 
management strategies, kidney cancer

None declared. Received on September 25, 2022 
Accepted on October 4, 2022 
This article has been peer reviewed.

Soc Int Urol J. 2022;3(6):424–436

DOI: 10.48083/OSES5540

2022 WUOF/SIU International Consultation on 
Urological Diseases: Active Surveillance for Small 
Renal Masses

Eric C. Kauffman,1 Mark W. Ball,2 Ravi Barod,3 Umberto Capitanio,4 Antonio Finelli,5 M. Carmen Mir,6 
Brian Shuch,7 Marc C. Smaldone,8 Maxine G.B. Tran,9 Phillip M. Pierorazio10

1 Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, United States 2 Urologic Oncology Branch, Center for Cancer Research, National Cancer 
Institute, National Institutes of Health, Bethesda, United States 3 Specialist Centre for Kidney Cancer, Royal Free Hospital, London, United Kingdom 4 Unit of Urology, 
Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy 5 Division of Urology, Department of Surgery, Princess 
Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada 6 Department of Urology, Fundación Instituto Valenciano Oncologia, 
Valencia, Spain 7 Department of Urology, University of California Los Angeles, Los Angeles, United States 8 Division of Urology and Urologic Oncology, Department of 
Surgical Oncology, Fox Chase Cancer Center, Philadelphia, United States 9 University College London Division of Surgery and Interventional Science and The Specialist 
Centre for Kidney Cancer at the Royal Free London Hospital, United Kingdom 10Division of Urology, Department of Surgery, University of Pennsylvania, Penn Medicine, 
Philadelphia, United States

Abstract

With greater awareness of indolence underlying small renal masses (SRM ≤ 4 cm) and the morbidity of invasive 
treatment, active surveillance for SRM patients is being increasingly utilized on an international level. This synopsis 
summarizes the 2022 review and expert opinion recommendations provided to the International Consultation of 
Urological Diseases (ICUD) by 10 urologists from high-volume active surveillance practices at international centers. 
Topics reviewed include SRM biology and clinical behavior, current national and international guidelines for active 
surveillance of SRM patients, active surveillance utilization patterns and barriers to implementation, outcomes and 
limitations of the active surveillance literature, criteria for active surveillance patient selection, protocols for active 
surveillance management including frequency/modality of imaging and the role of renal tumor biopsy, triggers 
for delayed intervention during active surveillance including tumor factors and patient factors, and pathological 
outcomes of delayed intervention. We conclude that despite limitations of the current literature, active surveillance  
is a safe initial management strategy for many SRM patients. The slow growth and low metastatic potential of SRMs, 
combined with no evidence to suggest oncologic compromise with delay to treatment, should provide confidence to 
both patients and providers who are considering active surveillance. Future research for prioritization should include 
characterization of long-term active surveillance outcomes including rates of metastasis and delayed intervention, 
standardization of objective tumor progression criteria for triggering delayed intervention, and further delineation of 
the role for active surveillance in young and healthy patients.

Introduction

Small renal masses (SRM) are renal cortical neoplasms ≤ 4 cm comprising benign tumors and renal cell carcinomas 
(RCC) with rare metastatic potential[1]. With greater use of cross-sectional abdominal imaging there has been a 
significant stage migration towards incidental SRM detection[2,3]. Conversely, RCC mortality has remained 
stable, establishing a concern for overtreatment of SRM patients and a rationale for active surveillance (AS). 

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AS is semantically distinct from watchful waiting 
(observation) and includes intention for curative delayed 
intervention (DI) if necessary, whereas watchful waiting/
observation involves only palliative treatment and 
concedes metastasis when cancer-specific mortality is 
unlikely[4].

Heterogenous and Indolent SRM Biology
SRM encompass a variety of benign and malignant 
histologic subtypes with different genomic and genetic 
landscapes. Benign tumors represent 20%–40% of 
SRM[5–8]. Malignant SRM are commonly low-grade 
and low-stage RCC, with high-grade and/or pT3 tumors 
accounting for only 10%–25% of surgical cases[5,7]. 
Regardless of histolog y, SR M rarely metastasize 
or become lethal. Risk of death from non-cancer 
causes is higher in almost all categories of patient age, 
comorbidity, and tumor size among patients with cT1 
tumors[9]. Analysis of tumor genomics and genetics by 
the TCGA and TRACERx next-generation sequencing 
initiatives indicate that cT1a RCC typically has low 
genetic diversity and chromosomal complexity, which 
may explain indolent clinical behavior[10–12]. This 
biology, termed the VHL mono driver subtype, is 
characterized by limited genetic branching without 
additional driver mutations, tumor size < 45 mm, 
and excellent long-term survival, often requiring 
decades to acquire mutations conducive to metastatic 
potential[11,12].

Guideline Support
C om mon ly u sed g u idel i ne s for SR M pat ient 
ma nagement include t hose from t he America n 
Urological Association (AUA), European Association 
of Urology (EAU), National Comprehensive Cancer 
Network (NCCN), American Society of Clinical 
Oncology (ASCO) and European Society of Medical 
Oncology (ESMO). There is general agreement that 
expectant management (AS or watchful waiting/
observation) is an option in patients with comorbidities 
or limited life expectancy (LE), and preferred whenever 
the anticipated risk of intervention outweighs the 
oncological benefits of treatment. However, patient 

selection criteria, role of renal tumor biopsy (RTB), 
modality/frequency of imaging, and triggers for DI 
all lack strong consensus recommendations. Current 
AUA[13,14] and NCCN[15] guidelines each make 
conditional recommendations to consider AS with 
potential for DI as a first-line management option in 
patients with a SRM < 2 cm, regardless of age or health, 
and in patients with a larger SRM when cystic or with 
significant comorbidity. EAU and ASCO support 
RTB to guide AS scanning frequency and/or initial 
patient selection, while AUA and ESMO recommend 
consideration of RTB in select cases for additional 
risk stratification[16–18]. There is general agreement 
for initial repeat imaging within 3–6 months. Specific 
patient-related and tumor-related factors favoring 
expectant management versus intervention are endorsed 
by the AUA (Table 1). However, many patients fall 
into a gray zone within this dichotomous scheme, and 
integration of additional factors is needed, as is attention 
to clinical scenarios in which contrasting factors are 
simultaneously present.

Current Utilization and Barriers
AS utilization has remained relatively static over the past 
20 years. SEER and NCDB population registries in the 
United States indicate that AS utilization rates for SRMs 
remain < 10%[19,20]. In contrast, use of both partial 
nephrectomy and thermal ablation has increased over 
this period, including in older patients[21]. There are 
currently no population-based studies of AS utilization 
in other countries. Recent reports of high AS utilization 
at some centers shed new light on potential barriers to 
broader AS utilization. Roswell Park Cancer Center 
reported that almost all (> 95%) new SRM patients 
seen over 5 years elected AS management, regardless of 
patient age or health[22], while MUSIC registry analyses 
reported considerably variable AS utilization across 
regional academic and private practices despite similar 
patient and tumor features[23]. Hence, factors related 
to the provider and health care setting, rather than to 
the patient, appear most important in driving current 
AS utilization. Provider-related differences may reflect 
variable awareness and/or certainty in interpreting the 
current evidence in support of AS.

Limitations of Active Surveillance 
Literature
Historically, AS was supported by only retrospective 
series, and the vast majority of reports are still subject to 
inherent retrospective design biases[24,25]. Definitions 
and protocols regarding AS were historically not well 
established, including substantial contamination 
with observation patients that potentially exaggerated 
metastasis rates, with DI deferral being typical upon 
SRM progression[26]. Reports are further confounded 

Abbreviations 
AS active surveillance
DI delayed intervention
GR growth rate
LE life expectancy
RCC renal cell carcinomas
RTB renal tumor biopsy
SRM small renal masses

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by variable inclusion of low complexity cysts (eg, 
Bosnia k I-III) without radiographic evidence of 
tumor, heterogeneous criteria for DI, and questionable 
reliability of follow-up to capture all metastatic and/or 
dying patients. Rarity of SRM metastasis and cancer-
specific death has challenged statistical comparisons 
to immediate treatment in both retrospective and 
prospective AS cohorts, and surrogates for clinical 
progression such as growth rate (GR) have unclear 
relevance to these gold-standard outcomes. It is possible 
if not likely that a subset of AS “failures,” particularly 
those with early metastasis (< 6–12 months), would 
not have benefited from immediate treatment[20,27]. 
Finally, follow-up for most AS studies remains relatively 
short (t y pica lly median 24–36 months), leav ing 
uncertainty regarding the long-term sustainability and 
safety. More prospective series with long-term follow-up 
using pre-defined objective criteria for selecting patients 
and triggering DI are needed.

Summation of Recent Active Surveillance 
Literature
Despite its limitations, the summation of published 
literature indicates that AS is a safe initial management 
strategy for many SRM patients. A 2018 systematic 
review of AS series from Mir et al. concluded relatively 
slow linear growth rates (median 0.37 cm/year overall, 
0.22 cm/year for SR Ms), and low metastasis and 
cancer-specific survival rates[28]. These conclusions 

are supported by more recent prospectively managed 
cohorts using AS protocols, differing in nuances of their 
prospective AS pathways but collectively providing 
strong support for oncologic safety. One of the largest 
registries is an American multi-institutional prospective 
cohort study comparing the outcomes of SRM patients 
undergoing AS versus primary intervention, the Delayed 
Intervention and Surveillance for Small Renal Masses 
(DISSRM) Registry. Initiated in 2009, DISSRM at last 
report included 495 AS patients with median follow-
up of 3.3 years and a third of patients followed for > 5 
years[29]. The 5-year progression-free survival in the AS 
group was 67% and was driven largely by either rapid 
GR or patient preference. The 7-year cancer-specific 
survival (CSS) with AS was 100% and not significantly 
different from other management strategies (98.8% 
for partial nephrectomy)[25,30]. Oncological safety 
of AS was similarly observed among carefully selected 
SRM patients < 60 years old[31]. The DISSRM registry 
has also provided data regarding GR variability over 
time, the minimal utility of routine chest imaging, and 
comparative outcomes for patient quality of life during 
AS versus other management strategies[25,32–34].

The prospective Renal Cell Cancer Consortium of 
Canada recently highlighted histology specific GR 
outcomes, with an overall average of 2–3mm/year 
during a median follow-up of 5.8 years[27,35]. RTB was 
encouraged at enrollment, and papillary type 1 renal cell 
carcinomas (RCC) demonstrated a significantly more 
indolent course than clear cell RCC, which had higher 

TABLE 1. 

Patient and tumor-related factors favoring active surveillance versus intervention according to the AUA guidelines

Patient-related factors Tumor factors

Favor Active Surveillance/  
Expectant Management 

Elderly 
Life expectancy < 5 years 
High comorbidities 
Excessive perioperative risk 
Poor functional status 
Marginal renal function 
Patient preference to avoid treatment risks

Tumor size < 3cm 
Tumor growth < 5mm/year 
Non-infiltrative on imaging 
Low complexity 
Favorable histology (if RTB performed)

Favor Intervention

Young 
Life expectancy > 5 years 
Low comorbidity 
Acceptable perioperative risk 
Good functional status 
Anticipate adequate renal function following 
intervention 
Patient preference for treatment

Tumor size > 3cm 
Tumor growth > 5mm/year 
Infiltrative on imaging 
High complexity 
Unfavorable histology (if RTB performed)

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GR and progression rates[35]. GR was variable within 
an individual patient, and rapidly growing tumors were 
frequently stable on subsequent imaging, suggesting 
value to a confirmatory scan. The 5-year progression-
free survival was 54%, driven mainly by elevated GR 
(82% of patients). Only a minority (36%) of 136 patients 
with biopsy-proven RCC remained on AS at 5 years, 
and 35% of nephrectomy DI patients had high-grade 
pathology, suggesting enrichment for adverse pathology 
(see also Delayed Intervention Pathology, below). Six 
RCC patients (4%, all clear cell subtype) developed 
metastasis and 29 (21%) died, including 3 (2%) cancer-
related deaths. These long-term outcomes mirror those 
of malignant SRM surgical series, and support the 
potential long-term durability of AS in a subset of RTB-
confirmed RCC patients.

Fox Chase Cancer Center has a long histor y of 
investigating AS for SRMs. In the most recent update, 
544 lesions in 457 patients over a median 67 months 
indicated that 80% of SRMs will grow slowly or not at all, 
approximately 40% will undergo intervention at 5 years, 
and cancer-specific mortality is 1%[36]. Data from this 
cohort support the safety of DI in SRM patients and, as 
for DISSRM and the Canadian registry, indicates rapid 
GR is associated with higher rates of intervention.

In a recent cohort series of “universal ” AS from 
Roswell Park Cancer Center, a ll non-hereditar y 
SRM patients seen by one urologist over a 5-year 
period were recommended AS if they lacked tumor 
progression criteria at presentation, which amounted 
to > 95% of consecutive new SRM patients[22]. Tumor 
progression criteria used for triggering immediate or 
delayed treatment were pre-defined as longest tumor 
diameter (LTD) > 4 cm, GR > 5 mm/year for LTD 
≤  3  cm or  >  3  mm/year for LTD > 3 cm, unfavorable 
RTB histology, cT3a stage, or SRM-related symptoms. 
Patients meeting any criterion were recommended 
treatment if LE was > 15 years, observation if LE was 
< 5 years, and continued AS versus DI if LE was 5–15 
years. Most patients tolerated AS, with only 1 patient 
(1%) crossing over to treatment due to non-tumor factors 
(anxiety). Of 128 patients, 75% remained DI-free at 3 
years, and none developed metastasis, which further 
supports AS safety.

Selecting Patients for Active Surveillance
While national and international consensus guidelines 
recommend AS patient selection based on tumor size, 
life expectancy, and comorbidities, very few strict 
size/age/comorbidity cut-offs exist[14,15,33]. Tumor 
and patient factors to guide AS patient selection are 
summarized below.

Tumor Factors
Tumor size
There is general consensus for LTD to guide AS patient 
selection, as the strongest known clinical predictor 
of SRM malignant histology, adverse pathology, and 
metastatic potential[5–8,34]. Metastasis rates approach 
0% for LTD < 2 cm, ~1% for < 3 cm, 2%–3% for < 4 cm, 
and increase exponentially for >  4  cm[9,37–43]. 
Currently, AUA and NCCN recommend consideration 
of AS independent of hea lt h in pat ients w it h 
LTD < 2 cm, while other guidelines are noncommittal 
regarding an LTD threshold. While < 2 cm is the most 
ideal for AS patient selection, we believe the current 
literature supports adequate oncologic safety to consider 
AS for patients with LTD up to 4 cm. However, more 
careful selection and/or monitoring (see below, Active 
Surveillance Protocols / Renal Mass Imaging; and 
Triggers For Delayed Intervention / Growth Rate) should 
be considered for patients with LTD 3–4 cm due to the 
non-negligible metastatic risk at this size.

Benign or unfavorable renal tumor biopsy 
histology
RTB can aid SRM risk stratification by: (1) identifying 
benign neoplastic histology (renal oncocy toma or 
angiomyolipoma, AML); or (2) revealing unfavorable 
RCC histolog y[17,22,27,44]. R isk of spontaneous 
hemorrhage observed with larger AML appears to 
be insignificant among SRMs[45]. Historically, RTB 
differentiation of oncocytoma from RCC (particularly 
chromophobe RCC) was challenged by histologic overlap 
necessitating diagnostic extirpation, but more reliable 
RTB diagnosis has evolved with immunohistochemistry 
panels that include the oncocytoma/chromophobe-
specif ic biomarker, CD117, and RCC biomarkers 
lacking in oncocytoma (eg, CK7, CAIX, AMACR, 
vimentin); in addition to radiologic approaches that 
corroborate oncocytoma diagnosis, such as Sestamibi 
scan and CT-based contrast enhancement measurement 
(tumor:cortex peak early enhancement ratio, or “PEER” 
score)[45–50]. Oncologic and functional safety of AS for 
oncocytomas is generally supported but requires more 
long-term study[51–54]. SRM patients with RTB favoring 
oncocytoma are ideal AS candidates, given the indolence 
of oncocytic SRMs regardless of malignant vs. benign 
etiology[55]. In contrast, unfavorable RTB histology 
(nuclear grade > 3, papillary type 2 RCC, translocation 
RCC, unclassif ied/indeterminable RCC subty pes) 
may challenge AS candidacy, although additional 
study is needed since even adverse histology may have 
outstanding outcomes among SRM patients[28]. The 
value of histologic subtyping among favorable RCC 
histologies (eg, low-grade clear cell vs. papillary type 1 
vs. chromophobe) remains unclear, although Canadian 

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registry investigators observed metastases exclusively 
with the clear cell subtype, while zero growth occurred 
more often among non-clear cell subtypes[35].

Cysts
Predominantly cystic tumors (Bosniak III-IV) are 
associated with more favorable pathology and prognosis 
compared to solid tumors of the same size, including 
only rare metastatic potential[56,57]. Moreover, AS for 
Bosniak III lesions of all sizes and smaller Bosniak IV 
lesions is associated with particularly excellent oncologic 
outcomes. Accordingly, there is general consensus that 
Bosniak III-IV SRMs comprise an ideal patient subset 
for AS consideration.

Patient Factors
Age and life expectancy
Other cause mortality outweighs the risk of cancer-
specific mortality for most SRM patients, particularly 
in elderly, but also regardless of age, comorbidity, tumor 
size or initial management strategy elected[43,58–60]. 
DISSRM and other registries support that patients >70 
years old and those with competing risks of mortality 
(particularly cardiovascular disease)[60] are most likely 
to benefit from and remain on AS[43,61,62]. Specific 
LE thresholds have not been routinely addressed. 
Among patients with LE <5 years, aggressive treatment 
(predominantly with surgery) has no known benefit 
but remains common, highlighting a need to better 
incorporate LE into treatment decision-making[63]. 
Age- and sex-adjusted LE calculators are available (e.g., 
https://www.ssa.gov/OACT/population/longevity.html), 
but methods to adjust based on comorbidities and frailty 
are not well standardized[64,65]. A health-adjusted 
renal mass-specific calculator was recently published 
by Psutka et al. including DISSRM registry patients  
(https://small-renal-mass-risk-calculator.fredhutch.
org)[43]. AS in young, healthy patients remains 
controversial, given the historical presumption that 
tumors would eventually grow and require intervention. 
However, DISSRM registry analysis recently showed 
that a significant proportion of younger patients (< 60 
years old) have a durable absence of significant growth, 
with 70% remaining on AS after 5 years and metastasis-
free[31]. Similarly, a 72% rate of AS continuation beyond 
5 years was reported in Roswell Park Cancer Center’s 
recently updated experience of AS recommended to over 
200 consecutive progression-free SRM patients without 
age-related or health-related selection bias, which 
yielded a relatively young and healthy AS cohort[66]. 
AS is thus likely to be safe for young, healthy patients 
with SRMs who wish to avoid immediate treatment, but 
counseling should mention the uncertainty of long-term 
(> 10 year) outcomes including DI rates.

Renal function
Any intervention on a renal unit will adversely affect 
the estimated glomerular filtration rate, with nephron-
sparing approaches generally incurring ipsilateral loss 
of 10%–20%[21]. AS is the only available management 
option that may not affect the natural history of 
chronic kidney disease progression[21,25,67]. Given 
associated risks for cardiac morbidity and other cause 
mortality[68], patients at risk for end-stage renal disease 
upon treatment are ideal candidates for AS[43]. Patients 
who already have end-stage renal disease may or may 
not require treatment to be eligible for renal transplant, 
depending on center-specific requirements[69].

Illness uncertainty/anxiety
Illness uncertainty and anxiety have historically played 
a major role in AS patient selection. The impact of the 
healthcare setting and provider on illness uncertainty 
is increasingly apparent. With the Roswell Park 
experience in which nearly all newly presenting SRM 
patients were recommended AS, there was surprisingly 
wide acceptance of AS enrollment after informed 
counseling (95% AS, 1% immediate treatment, 4% 
unknown), including 100% AS election among patients 
with follow-up at Roswell Park[22]. A structured AS 
program, consultation with a RCC expert/specialist, and 
availability of RTB histology may all influence illness 
uncertainty and AS enrollment.

Active Surveillance Protocols
AS protocols include periodic renal mass imaging, 
renal function monitoring, and periodic staging for 
metastatic progression, with or without adjunct use 
of RTB[70]. Meaningful comparisons of protocols 
have been challenged by the rarity of SRM metastasis 
or cancer-specific mortality outcomes to evaluate 
protocol efficacy[21]. In the absence of level 1 evidence, 
prospective cohort studies with rigorous patient and 
clinician adherence to meticulously defined eligibility 
criteria and strict surveillance schedules are critical to 
determining optimal surveillance protocols.

Renal Mass Imaging: Timing, Frequency  
and Modality
Most prospective protocols use multiphasic cross-
sectional imaging initially, with a long-term goal for 
ultrasound of more indolent masses to minimize 
radiation and contrast exposures[22,30,35]. All major 
studies to date include initial short-term surveillance, 
typically within 3–6 months to rule out very rapid 
growth, and subsequently follow patients at intervals 
extending from 6–12 months[22,27,30,36]. The next 
iteration of nuanced imaging may involve intervals 
based on initial tumor size, as, for example, the 

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Roswell Park protocol recommends an initial 3-month 
versus 6-month scan for tumors > 3 cm versus < 3 cm, 
respectively[22].

Renal Function and Metastatic Evaluation
Renal functional tests including a serum creatinine should 
occur at least annually[13,16]. Baseline chest imaging 
to rule out pulmonary metastasis is recommended[37]. 
However, the utility of subsequent chest monitoring is 
questionable, given the metastatic risk approaches 0% 
in the absence of significant SRM growth[20]; and there 
are definite psychologic, medical and financial harms to 
incidental pulmonary findings. Approximately 20% of 
chest imaging tests evaluated in the DISSRM registry 
were abnormal, of which most were non-actionable (no 
metastases)[34]. Annual chest imaging can likely be 
omitted or at least reduced in frequency unless there is 
(1) an abnormality on baseline imaging, (2) significant 
SRM growth, or (3) plans for DI[70].

Renal Tumor Biopsy
RTB utilization has increased over the past decade 
because of systematic reviews and meta-analyses 
supporting a high diagnostic rate and excellent safety 
profile[71,72]. This evolution in practice is evident 
from a DISSRM study showing an increase in RTB 
utilization over the past decade from 5% to 20%, while 
other contemporary AS cohorts surpass 50%[22,27,32]. 
While guideline committee recommendations vary, 
there is growing consensus that RTB can be useful to 
risk-stratify for AS but is not a requisite. There is also 
growing consensus to reserve RTB for SRMs with LTD 
>2 cm, given that smaller sizes have negligible oncologic 
risk and lower technical success rates[4,7,22]. Some 
programs, such as at Roswell Park and in Bologna, Italy, 
additionally endorse RTB in smaller (< 2 cm) tumors 
whenever there is a rapid GR (> 5 mm/year) to rule out 
benign tumor histology before DI conversion[22,73]. 
While some AS centers such as the Canadian registry 
and Roswell Park endorse routine RTB for AS guidance 
(i.e, > 50% of patients)[22,35], other contemporary AS 
programs use RTB more selectively based on variable 
patient- and program-specific thresholds (8%–24% of 
patients)[29,36,74,75]. In the DISSRM registry, patients 
are not routinely biopsied at enrollment, but RTB is 
recommended for GR >5mm/year or upon surpassing 
patient-specific LTD size thresholds (2, 3, or 4 cm)[29].

Triggers for Delayed Intervention
DI should be triggered during AS by any change that 
causes the oncologic risk to exceed the treatment 
risk[4,15–17]. This guiding principle mirrors that for 
initial AS selection, but utilizes growth kinetics and 
potentially new histology information obtained during 
AS to further improve risk stratification[22]. 

As with AS patient selection, DI triggers are divided into 
tumor factors and patient factors. Recent maturation of 
oncologic safety data has fostered patient and physician 
comfort with AS, and DI cases are increasingly triggered 
by tumor factors rather than patient factors/anxiety. 
Nevertheless, patient factors remain impactful and 
drive high variability between different AS programs in 
contemporary DI rates (11%–50%)[22,27,35,36,74–82].

Tumor Factors / Progression Criteria for 
Intervention
Tumor factors for DI have been referred to as progression 
criteria for intervention (PCI), so as to differentiate from 
classic clinical progression (i.e. stage, grade, death), since 
the former may not include the latter[22]. PCI generally 
fall within 5 categories (acronym: “GLASS”): (1) GR; 
(2) LTD; (3) Adverse/unfavorable biopsy histology; 
(4) Stage/infiltration; (5) Symptoms/signs. Based on 
both incidence and consensus level, GR and LTD are 
considered major PCI, whereas other GLASS PCI 
categories are minor. Only few centers use minor PCI, 
with Roswell Park observing < 3% versus 30% of patients 
meeting minor PCI versus major PCI, respectively[22]. 
Greater PCI standardization has been challenged by 
inconsistent usage of prospectively defined objective 
PCI thresholds[22,27,35,74–81], as nonspecific subjective 
tumor thresholds are still commonly reported (eg, “fast” 
or “significant” growth, “radiological progression,” 
“change in SRM’s features,” etc.)[73,75–77]. This hetero-
geneity drives high variability in reported PCI rates 
(9%–30%)[22,27,75].

Growth rate
Rapid GR is the most commonly used PCI in contempo-
rary AS series[22,35,73–75,78,80,82], and also the 
most common DI trigger when used with other 
PCI[22,35]. Numerous retrospective studies support 
GR association with RCC grade[22,74,83–86] metastatic 
potential[20,75,77,79,80,82,86], and an association 
between rapid GR and clear cell RCC histology is also 
reported[35]. However, prospective validation of these 
associations is still needed[52,75]. A systematic review of 
early AS series identified a median GR of 6.5 mm/year 
among metastatic patients compared with 2.5 mm/year 
in non-metastatic patients[20], and the vast majority of 
the > 30 AS patient metastases reported to date have had 
a primary tumor GR > 5 mm/year[29,35,75,77,79,80,82]. 
However, most of these patients were not followed 
with prospectively applied PCI and had quite large 
primary tumors (> 6 cm) at metastasis, and validation 
in SRM cohorts managed with timely DI conversion 
is needed[36,78]. Nevertheless, there is consensus, 
including from ASCO and AUA to use GR of > 5 mm/
year to trigger DI[4,15,17]. Studies prospectively using 
GR > 5 mm/year suggest that 13%–18% of patients meet 
this threshold during AS[22,56,74,78]. Tumor size-

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stratified GR thresholds may have future utility. For 
example, Roswell Park prospectively uses GR > 5 mm/
year for LTD ≤ 3 cm, but GR > 3 mm/year for LTD > 
3 cm, based on (1) increased/non-negligible SRM 
metastatic risk beyond 3 cm; (2) historical reports of 
SRM metastasis with GR < 5 mm/year but not < 3 mm/
year; and (3) high likelihood that a SRM > 3 cm with 
GR > 3 mm/year will progress based on LTD > 4 cm 
within 1–3 years anyway[22]. An alternative to linear 
GR is volumetric growth or doubling rate, as used by 
the Canadian RCC Consortium and University of 
Texas Southwestern Medical Center[27,35,80]. However, 
caution with this approach must be exercised, since 
minute linear changes in very small SRMs (including 
those attributable to artifact/inter-observer variability) 
can yield volumetric doubling, while relatively fast 
linear growth (eg, ~6–8 mm/year) may fail to meet the 
volumetric doubling threshold for tumors > 4 cm.

Longest tumor diameter
In a systematic review of early AS series including 
over 800 patients, 89% (16/18) of metastatic patients 
had LTD > 4 cm at metastasis versus 0% (0/18) having 
LTD < 3 cm[20]. Contemporary AS series similarly 
support a negligible metastatic rate when <3cm, and 
a very low metastatic rate for LTD 3–4 cm, with most 
metastases occurring when > 4 cm[29,56,76,78,80,81,83]. 
Accordingly, there is strong general consensus for LTD 
usage as a PCI[4,16,17,87], with 4 cm being the most 
commonly used threshold. LTD > 4 cm triggered or 
helped trigger 25% and 50% of DI cases in the Canadian 
and Roswell Park cohorts, respectively[22,35]. A > 3 cm 
LTD cutoff for treatment is endorsed by current AUA 
guidelines, but its reported use is uncommon[4,29,77]. 
One rationale for using LTD > 3 cm is its association 
with higher rates of eventual DI[22,29,31]. Nevertheless, 
a 3 cm threshold likely overtreats many patients, 
particularly those with slow growth (< 3 mm/year) for 
whom metastasis rates appear to approach zero and 
long-term DI avoidance may be possible.

Adverse/unfavorable biopsy histology
Although the prevalence and diagnostic sensitivity of 
RTB for adverse histology in SRMs is low, diagnostic 
specificity is high. Accordingly, any patient with RTB 
favoring high-grade RCC and/or a more aggressive 
subtype should be counseled on potentially higher risks 
with AS continuation, given the higher metastatic risk in 
surgical series.

Stage/infiltration
Clinical upstaging from cT1a to cT3a is an independent 
prognostic variable for metastasis but is a rare event in 
most AS series. Only one patient (1%) in the Roswell 
cohort developed cT3a disease (progressing also by both 
GR and LTD)[22]. Similarly, Canadian investigators 

reported one (1%) patient with DI triggered by tumor 
thrombus[75]. Regardless of rarity, detection of cT3a 
upstaging should trigger DI consideration due to a 
potentially higher metastatic risk.

Symptoms/signs
Tumor-related symptoms or signs such as gross 
hematuria, retroperitoneal bleeding, or paraneoplastic 
effects are well described for RCC but exceedingly rare 
in the SRM population. Accordingly, the vast majority 
of SRMs remain asymptomatic during AS[22,75]. In 
over 500 patients to date, the DISSRM registry has yet 
to encounter gross hematuria attributable to a renal 
mass[29]. Three (18%) patients in a prospective Canadian 
study and one (1%) patient in the Roswell Park cohort 
developed gross hematuria, although a renal source is 
unclear. For symptom development during AS, the first 
action should be to rule out other sources.

Patient Factors
With the exception of a few recent AS series in which 
DI was almost entirely driven by PCI[22,35,73], DI cases 
in contemporary AS reports are still commonly, if not 
mostly, performed because of patient factors without 
PCI development[7,27,74,76,82,88].

Patient preference/anxiety
Patient preference due to anxiety or disease uncertainty 
is the most common patient factor triggering DI. This 
is clearly demonstrated in the DISSRM and Canadian 
prospective registries where approximately 50% or more 
of patients who crossover to DI do so without tumor 
PCI development[27,76,78,82,88]. Illness uncertainty 
predicts general quality of life, cancer-specific quality 
of life, and distress which can all impact the success 
of AS[89]. Interestingly, mental health scores improve 
over time in patients in a structured AS program 
such as DISSRM[33]. The increasingly apparent role 
of the provider and health care setting in influencing 
AS program acceptance was discussed above. Only 
rarely did AS patients convert to DI because of anxiety 
without PCI development in the Roswell Park (1%) and 
Italian (4%) cohorts, supporting this role[22,73]. Given 
the impact of illness uncertainty during AS[89], DI 
conversion may be reduced by empowering the patient 
upfront with details regarding the very low GR (e.g., 
average 2–3 mm/year), planned use of PCI thresholds, 
and negligible expected metastasis rates during PCI 
freedom. The DISSRM registry demonstrates that 
patients experience improving mental health domains 
while they are in structured AS programs, indicating 
reductions in anxiety and illness uncertainty[33].

Life expectancy
LE must be carefully considered before DI conversion, 
since impending metastasis may not increase mortality 
risk when life expectancy is limited (eg, < 5 years)[90].  

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In young hea lthy indiv idua ls, PCI development 
should serve as an absolute indication for DI, whereas 
AS continuation or observation conversion may be 
appropriate in elderly patients and/or patients with 
comorbidities despite PCI development. Improved 
patient health or resolution of an acute health issue 
during AS may increase LE and change the risk-benefit 
ratio towards treatment[82]. More recent cohorts, like 
that at Roswell Park, have integrated PCI triggers with 
LE calculations to guide decision-making regarding DI 
conversion[22].

Other patient factors
Other patient factors triggering DI are uncommon. The 
need for unrelated additional surgery is reported as a 
DI trigger[91], but, other than renal transplantation, is 
generally not endorsed. Concern for losing a window 
to perform nephron-sparing treatment may raise 
consideration for early DI, but the vast majority of DI 
cases in contemporary AS reports have been amenable 
to nephron-sparing, suggesting no compromise in renal 
preservation[22,35,73,74,76–80,88]. Rarely, AS patients 
may develop end-stage renal disease that requires 
resection to qualify for renal transplantation eligibility, 
depending on center requirements[70,79]. Finally, 
concern regarding patient non-compliance may be 
an under-utilized reason for DI conversion, given that 
many metastasis cases during AS have been attributed to 
poor patient adherence to AS protocols[20,79].

Delayed Intervention Pathology
Most AS series demonstrate a similar albeit slightly 
higher rate of malignancy at DI (80%–100%) compared 
to surgical SRM series[8,22,27,36,73,78,82]. Avoidance 
of benign resections appears to correlate with degree 
of RTB usage, with the Canadian consortium and 
Roswell Park each achieving a 0% benign DI resection 
rate while using routine RTB to identify benign tumors 
non-surgically[6,22,27,73,78]. High nuclear grade or 
pT3 upstaging is uncommon in resected SRM series 

and AS series, comprising ~5% and 10%–20% of cases, 
respectively[78,86,92–96]. In contrast, Roswell Park 
recently reported very high rates (62%) of any adverse 
pathology at DI surgeries, which may relate to keeping 
99% of patients on AS until pre-defined tumor PCI 
development, potentially enriching DI resections 
for higher risk tumors[22]. These investigators also 
found a rapid GR to be associated with higher adverse 
pathology rates, similar to many retrospective series. 
However a DI cohort study from the DISSRM registry 
observed low rates of adverse pathology and zero 
metastases, regardless of GR[78]. The clinical impact of 
adverse pathology at DI remains unclear since resected 
SRM patients have an excellent prognosis regardless of 
pathology.

On the Horizon
A variety of technologic advances under active study 
have the potential to propel the AS field forward. These 
approaches include the use of novel tumor biopsy-based 
biomarkers, blood-based biomarkers (e.g., circulating 
tumor cells/DNA), and urine-based biomarkers, which 
may improve prognostic accuracy over conventional 
imaging and biopsy histology. Radiomics guided by 
automated volumetry and/or artificial intelligence may 
also further refine current AS strategies.

Summary
Despite limitations in the current literature, AS appears 
to be a safe initial management strategy for many SRM 
patients. The indolent clinical growth and low metastatic 
potential of SRMs, combined with no evidence to 
suggest oncologic compromise with delays to treatment, 
should provide confidence to both patients and providers 
who are considering AS. Future research in AS patients 
should prioritize characterization of long-term rates of 
metastasis and DI, standardization of objective tumor 
progression criteria for triggering DI, and defining the 
role of AS in young and healthy patients.

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References

1. Gill IS, Aron M, Gervais DA, Jewett MAS. Clinical practice. Small 
renal mass. N Engl J Med.2010;362(7):624-634. doi:10.1056/
NEJMcp0910041

2. Kane CJ, Mallin K, Ritchey J, Cooperberg MR, Carroll PR. Renal cell 
cancer stage migration: analysis of the National Cancer Data Base. 
Cancer.2008;113(1):78-83. doi:10.1002/cncr.23518

3. Patel HD, Gupta M, Joice GA, Srivastava A, Alam R, Allaf ME, et 
al. Clinical stage migration and survival for renal cell carcinoma in 
the United States. Eur Urol Oncol.2019;2(4):343-348. doi:10.1016/j.
euo.2018.08.023

4. Campbell S, Uzzo RG, Allaf ME, Bass EB, Cadeddu JA, Chang 
A, et al. Renal mass and localized renal cancer: AUA Guideline. J 
Urol.2017;198(3):520-529. doi:10.1016/j.juro.2017.04.100

5. Bhindi B, Thompson RH, Lohse CM, Mason RJ, Frank I, Costello BA, 
et al. The probability of aggressive versus indolent histology based 
on renal tumor size: implications for surveillance and treatment. Eur 
Urol.2018;74(4):489-497. doi:10.1016/j.eururo.2018.06.003

6. Johnson DC, Vukina J, Smith AB, Meye A-M, Wheeler SB, Kuo 
T-M, et al. Preoperatively misclassified, surgically removed benign 
renal masses: a systematic review of surgical series and United 
States population level burden estimate. J Urol.2015;193(1):30-35. 
doi:10.1016/j.juro.2014.07.102

7. Patel HD, Semerjian A, Gupta M, Pavlovich CP, Johnson MH, Gorin 
MA, et al. Surgical removal of renal tumors with low metastatic 
potential based on clinical radiographic size: A systematic review 
of the literature. Urol Oncol.2019;37(8):519-524. doi:10.1016/j.
urolonc.2019.05.013

8. Kim JH, Li S, Khandwala Y, Chung KJ, Park HK, Chung BI. Association 
of prevalence of benign pathologic findings after partial nephrectomy 
with preoperative imaging patterns in the United States From 
2007 to 2014. JAMA Surg.2019;15 4 (3):225-231. doi:10.1001/
jamasurg.2018.4602

9. Patel HD, Kates M, Pierorazio PM, Hyams ES, Gorin MA, Ball MW, 
et al. Survival after diagnosis of localized T1a kidney cancer: current 
population-based practice of surgery and nonsurgical management. 
Urology.2014;83(1):126-132. doi:10.1016/j.urology.2013.08.088

10. C ancer Genome Atlas Research Net work . Comprehensive 
molecular characterization of clear cell renal cell carcinoma. 
Nature.2013;499(7456):43-49. doi:10.1038/nature12222

11. Turajlic S, Xu H, Litchfield K, Rowan A, Horswell S, Chambers T, et 
al. Deterministic evolutionary trajectories influence primary tumor 
growth: TRACERx Renal. Cell.2018;173(3):595-610.e11. doi:10.1016/j.
cell.2018.03.043

12. Mitchell TJ, Turajlic S, Rowan A, Nicol D, Farmery JHR, O'Brien T, et 
al. Timing the landmark events in the evolution of clear cell renal cell 
cancer: TRACERx Renal. Cell.2018;173(3):611-623.e17. doi:10.1016/j.
cell.2018.02.020

13. Campbell SC, Clark PE, Chang SS, Karam JA, Souter L, Uzzo RG. Renal 
mass and localized renal cancer: evaluation, management, and follow-
up: AUA Guideline: Part I. J Urol.2021;206(2):199-208. doi:10.1097/
JU.0000000000001911

14. Campbell SC, Uzzo RG, Karam JA, Chang SS, Clark PE, Souter L. Renal 
mass and localized renal cancer: evaluation, management, and follow-
up: AUA Guideline: Part II. J Urol.2021;206(2):209-218. doi:10.1097/
JU.0000000000001912

15. Motzer RJ, Jonasch E, Boyle S, Carlo MI, Manley B, Agarwal N, et al. 
NCCN guidelines insights: kidney cancer, version 1.2021. J Natl Compr 
Canc Netw.2020;18(9):1160-1170. doi:10.6004/jnccn.2020.0043

16. Ljungberg B, Albiges L, Abu-Ghanem Y, Bensalah K, Dabestani S, 
Fernández-Pello S,et al. European Association of Urology Guidelines on 
Renal Cell Carcinoma: The 2019 Update. Eur Urol.2019;75(5):799-810. 
doi:10.1016/j.eururo.2019.02.011

17. Finelli A, Ismaila N, Bro B, Durack J, Eggener S, Evans A, et al. 
Management of Small Renal Masses: American Society of Clinical 
Oncology Clinical Practice Guideline. J Clin Oncol.2017;35(6):668-680. 
doi:10.1200/JCO.2016.69.9645

18. Escudier B, Porta C, Schmidinger M, Rioux-Leclercq, Bex A, Khoo 
V, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines 
for diagnosis, treatment and follow-up†[†Approved by the ESMO 
Guidelines Committee: September 2008, last update January 2019. 
This publication supersedes the previously published version—Ann 
Oncol.2016; 27 (Suppl 5): v58–v68.] Ann Oncol.2019;30(5):706-720. 
doi:10.1093/annonc/mdz056

19. Yang G, Villalta JD, Meng MV, Whitson JM. Evolving practice 
patterns for the management of small renal masses in the USA. BJU 
Int.2012;110(8):1156-1161. doi:10.1111/j.1464-410X.2012.10969.x

20. Smaldone MC, Kutikov A, Egleston BL, Canter DJ, Viterbo R, Chen 
DY T, et al. Small renal masses progressing to metastases under 
active sur veillance: a systematic review and pooled analysis. 
Cancer.2012;118(4):997-1006. doi:10.1002/cncr.26369

21. Pierorazio PM, Johnson MH, Patel HD, Sozio SM, Sharma R, Lyoha 
E, et al. Management of renal masses and localized renal cancer: 
systematic review and meta-analysis. J Urol.2016;196(4):989-999. 
doi:10.1016/j.juro.2016.04.081

22. Menon AR, Hussein A A, Attwood KM, White T, James G, Xu B, 
et al. Active surveillance for risk stratification of all small renal 
masses lacking predefined clinical criteria for inter vention.  
J Urol.2021;206(2):229-239. doi:10.1097/JU.0000000000001714

432 SIUJ  •  Volume 3, Number 6  •  November 2022 SIUJ.ORG

2022 WUOF/SIU INTERNATIONAL CONSULTATION ON UROLOGICAL DISEASES

http://SIUJ.org


23. Patel AK, Rogers CG, Johnson A, Noyes SL, Qi J, Miller D, et al. Initial 
observation of a large proportion of patients presenting with clinical 
stage T1 renal masses: results from the MUSIC-KIDNEY statewide 
collaborative. Eur Urol Open Sci.2020;23:13-19. doi:10.1016/j.
euros.2020.11.002

24. Chawla SN, Crispen PL, Hanlon AL, Greenberg RE, Chen DYT, Uzzo 
RG. The natural history of observed enhancing renal masses: meta-
analysis and review of the world literature. J Urol.2006;175(2):425-
431. doi:10.1016/S0022-5347(05)00148-5

25. Alam R, Patel HD, Osumah T, Srivastava A, Gorin MA, Johnson 
MH, et al. Comparative effectiveness of management options for 
patients with small renal masses: a prospective cohort study. BJU 
Int.2019;123(1):42-50. doi:10.1111/bju.14490

26. Ristau BT, Correa AF, Uzzo RG, Smaldone MC. Active surveillance 
for the small renal mass: growth kinetics and oncologic outcomes. 
Urol Clin North Am.2017;44(2):213-222. doi:10.1016/j.ucl.2016.12.007

27. Jewett MAS, Mattar K, Basiuk J, Morash CG, Paulter SE, Siemens DR, 
et al. Active surveillance of small renal masses: progression patterns 
of early stage kidney cancer. Eur Urol.2011;60(1):39-44. doi:10.1016/j.
eururo.2011.03.030

28. Mir MC, Capitanio U, Bertolo R, Ouzaid I, Salagierski M, Kriegmair M, 
et al. Role of active surveillance for localized small renal masses. Eur 
Urol Oncol.2018;1(3):177-187. doi:10.1016/j.euo.2018.05.001

29. Cheaib JG, Alam R, Kassiri B, Biles M, Metcalf M, Wlanjnitz 
T, et al. Active surveillance for small renal masses is safe and 
non-inferior: 10-year update from the DISSRM registry. Eur Urol Open 
Sci.2020;19:e945-e946. doi:10.1016/S2666-1683(20)33210-9

30. Pierorazio PM, Johnson MH, Ball MW, Gorin MA, Trock BJ, Chang P, 
et al. Five-year analysis of a multi-institutional prospective clinical 
trial of delayed intervention and surveillance for small renal masses: 
the DISSRM registry. Eur Urol.2015;68(3):408-415. doi:10.1016/j.
eururo.2015.02.001

31. Metcalf MR, Cheaib JG, Biles MJ, Patel HD, Peña VN, Chang P, 
et al. Outcomes of active surveillance for young patients with 
small renal masses: prospective data from the DISSRM Registry.  
J Urol.2021;205(5):1286-1293. doi:10.1097/JU.0000000000001575

32. Uzosike AC, Patel HD, Alam R, Schwen ZR, Gupta M, Gorin MA, et al. 
Growth kinetics of small renal masses on active surveillance: variability 
and results from the DISSRM Registry. J Urol.2018;199(3):641-648. 
doi:10.1016/j.juro.2017.09.087

33. Patel HD, Riffon MF, Joice GA, Johnson MH, Chang P, Wagner AA, 
et al. A prospective, comparative study of quality of life among 
patients with small renal masses choosing active surveillance and 
primary intervention. J Urol.2016;196(5):1356-1362. doi:10.1016/j.
juro.2016.04.073

34. Kassiri B, Cheaib JG, Pierorazio PM. Patients with small renal masses 
undergoing active surveillance-is yearly chest imaging necessary? 
J Urol.2019;201(6):1061-1063. doi:10.1097/JU.0000000000000079

35. Finelli A, Cheung DC, Al-Matar A, Evans AJ, Morash CG, Paulter 
SE, et al. Small renal mass surveillance: histology-specific growth 
rates in a biopsy-characterized cohort. Eur Urol.2020;78(3):460-467.
doi:10.1016/j.eururo.2020.06.053

36. McIntosh AG, Ristau BT, Ruth K, Jennings R, Ross E, Smaldone 
MC, et al. Active surveillance for localized renal masses: tumor 
growth, delayed intervention rates, and >5-yr clinical outcomes. Eur 
Urol.2018;74(2):157-164. doi:10.1016/j.eururo.2018.03.011

37. Thompson RH, Hill JR, Babayev Y, Cronin A, Kaag M, Kundu S, et 
al. Metastatic renal cell carcinoma risk according to tumor size. J 
Urol.2009;182(1):41-45. doi:10.1016/j.juro.2009.02.128

38. Umbreit EC, Shimko MS, Childs MA, Lohse CM, Cheville JC, Leibovich 
BC, et al. Metastatic potential of a renal mass according to original 
tumour size at presentation. BJU Int.2012;109(2):190-194; discussion 
194. doi:10.1111/j.1464-410X.2011.10184.x

39. Mano R, Duzgol C, Ganat M, Goldman DA, Blum K A, Silagy AW, 
et al. Preoperative nomogram predicting 12-year probability of 
metastatic renal cancer – evaluation in a contemporary cohort. Urol 
Oncol.2020;38(11):853.e1-853.e7. doi:10.1016/j.urolonc.2020.07.019

40. Walther MM, Choyke PL, Glenn G, Lyne JC, Rayford W, Venzon 
D, et al. Renal cancer in families with hereditary renal cancer: 
prospective analysis of a tumor size threshold for renal parenchymal 
sparing surger y. J Urol.1999;161(5):1475 -1479. doi:10.1016/
S0022-5347(05)68930-6

41. Stewart-Merrill SB, Thompson RH, Boorjian SA, Psutka SP, Lohse 
CM, Cheville JC, et al. Oncologic surveillance after surgical resection 
for renal cell carcinoma: a novel risk-based approach. J Clin 
Oncol.2015;33(35):4151-4157. doi:10.1200/JCO.2015.61.8009

42. Duffey BG, Choyke PL, Glenn G, Grubb RL, Venzon D, Linehan WM, 
et al. The relationship between renal tumor size and metastases in 
patients with von Hippel-Lindau disease. J Urol.2004;172(1):63-65. 
doi:10.1097/01.ju.0000132127.79974.3f

43. Psutka SP, Gulati R, Jewett MAS, Fadaak K, Finelli A, Legere L, et al. 
A clinical decision aid to support personalized treatment selection 
for patients with clinical T1 renal masses: results from a multi-
institutional competing-risks analysis. Eur Urol.2022 Jun;81(6):576-
585. doi:10.1016/j.eururo.2021.11.002 Epub 2021 Nov 30.

44. Richard PO, Jewett MAS, Bhatt JR, Evans AJ, Timilsina N, Finelli 
A. Active surveillance for renal neoplasms with oncocytic features 
is safe. J Urol.2016;195(3):581-586. doi:10.1016/j.juro.2015.09.067

45. Bhatt JR, Richard PO, Kim NS, Finelli A, Manickavachagam K, Legere 
L, et al. Natural history of renal angiomyolipoma (AML): most patients 
with large AMLS >4cm can be offered active surveillance as an initial 
management strategy. Eur Urol.2016;70(1):85-90. doi:10.1016/j.
eururo.2016.01.048

433SIUJ.ORG SIUJ  •  Volume 3, Number 6  •  November 2022

Active Surveillance for Small Renal Masses

http://SIUJ.org


46. Amin J, Xu B, Badkhshan S, Creighton TT, Abbotoy D, Murekeyisoni 
C, et al. Identification and validation of radiographic enhancement 
for reliable differentiation of CD117(+) benign renal oncocytoma and 
chromophobe renal cell carcinoma. Clin Cancer Res.2018;24(16):3898-
3907. doi:10.1158/1078-0432.CCR-18-0252

47. Gorin MA, Rowe SP, Baras AS, Solnes LB, Ball MW, Pierorazio PM, 
et al. Prospective evaluation of (99m)Tc-sestamibi SPECT/CT for the 
diagnosis of renal oncocytomas and hybrid oncocytic/chromophobe 
tumors. Eur Urol.2016;69(3):413-416. doi:10.1016/j.eururo.2015.08.056

48. Nikpanah M, Xu Z, Jin D, Farhadi F, Saboury B, Ball MW, et al. A deep-
learning based artificial intelligence (AI) approach for differentiation of 
clear cell renal cell carcinoma from oncocytoma on multi-phasic MRI. 
Clin Imaging.2021;77:291-298. doi:10.1016/j.clinimag.2021.06.016

49. Kahn AE, Lomax SJ, Bajalia EM, Ball CT, Thiel DD. Utility of the 
aortic-lesion-attenuation-difference (ALAD) and peak early-phase 
enhancement ratio (PEER) to differentiate benign from malignant renal 
masses. Can J Urol.2020;27(4):10278-10284.

50. Baghdadi A, Aldhaam NA, Elsayed AS, Hussein A A, Cavuoto LA, 
Kauffman E, et al. Automated differentiation of benign renal 
oncocytoma and chromophobe renal cell carcinoma on computed 
tomography using deep learning. BJU Int.2020;125(4):553-560. 
doi:10.1111/bju.14985

51. Cheema A, Menon A, White T, James G, Kauffman E. Mp80-19 
[abstract]Is renal volume and function compromised in oncocytoma 
patients on active surveillance? J Urol.2020;203(Suppl 4):e1233-e1234. 
doi:10.1097/JU.0000000000000972.019

52. Deledalle FX, Ambrosetti D, Durand M, Michel F, Baboudjian M, 
Gondran-Tellier B, et al. Active surveillance for biopsy proven renal 
oncocytomas: outcomes and feasibility. Urology.2021;156:185-190. 
doi:10.1016/j.urology.2021.05.034

53. Meagher MF, Lane BR, Capitanio U, Mehrazin R, Bradshaw AW, Noyes 
S, et al. Comparison of renal functional outcomes of active surveillance 
and partial nephrectomy in the management of oncocytoma. World J 
Urol. 2021;39(4):1195-1201. doi:10.1007/s00345-020-03299-5

54. Miller BL, Mankowski Gettle L, Van Roo JR, Ziemlewicz TJ, Best 
SL, Wells SA, et al. Comparative analysis of surger y, thermal 
ablation, and active surveillance for renal oncocytic neoplasms. 
Urology.2018;112:92-97. doi:10.1016/j.urology.2017.09.016

55. Flack CK, Calaway AC, Miller BL, Picken MM, Gondim DD, Idrees 
MT, et al. Comparing oncologic outcomes in patients undergoing 
surgery for oncocytic neoplasms, conventional oncocytoma, and 
chromophobe renal cell carcinoma. Urol Oncol.2019;37(11):811.e17-811.
e21. doi:10.1016/j.urolonc.2019.06.002

56.  Winters BR, Gore JL, Holt SK, Harper JD, Lin DW, Wright JL. Cystic 
renal cell carcinoma carries an excellent prognosis regardless 
of tumor size. Urol Oncol.2015;33(12):505.e9-13. doi:10.1016/j.
urolonc.2015.07.017

57. Chandrasekar T, Ahmad AE, Fadaak K, Jhaveri K, Bhatt JR, Jewett 
MAS, et al. Natural history of complex renal cysts: clinical evidence 
suppor ting active sur veillance. J Urol. 2018;199(3):633-6 4 0. 
doi:10.1016/j.juro.2017.09.078

58. Sun M, Becker A, Tian Z, Roghmann F, Abdollah F, Larouche A, et 
al. Management of localized kidney cancer: calculating cancer-
specific mortality and competing risks of death for surgery and 
nonsurgical management. Eur Urol.2014;65(1):235-241. doi:10.1016/j.
eururo.2013.03.034

59. Kutikov A, Egleston BL, Wong YN, Uzzo RG. Evaluating overall 
survival and competing risks of death in patients with localized 
renal cell carcinoma using a comprehensive nomogram. J Clin 
Oncol.2010;28(2):311-317. doi:10.1200/JCO.2009.22.4816

60. Patel HD, Kates M, Pierorazio PM, Allaf ME. Balancing cardiovascular 
and cancer death among patients with small renal mass: modification 
by cardiovascular risk. BJU Int.2015;115(1):58-64. doi:10.1111/bju.12719

61. Sotimehin AE, Patel HD, Alam R, Gorin MA, Johnson MH, Chang 
P, et al. Selecting patients with small renal masses for active 
surveillance: a domain based score from a prospective cohort study. 
J Urol.2019;201(5):886-892. doi:10.1097/JU.0000000000000033

62. Jacobs BL, Tan HJ, Montgomery JS, Weizer AZ, Wood DP, Miller DC, et 
al. Understanding criteria for surveillance of patients with a small renal 
mass. Urology.2012;79(5):1027-1032. doi:10.1016/j.urology.2011.12.052

63. Daskivich TJ, Tan HJ, Litwin MS, Hu JC. Life expectancy and variation 
in treatment for early stage kidney cancer. J Urol.2016;196(3):672-677. 
doi:10.1016/j.juro.2016.03.133

64. Cho H, Klabunde CN, Yabroff KR, Wang Z, Meekins A, 
L a n s d o r p - Vo g e l a a r  I ,  e t  a l .  C o m o r b i d i t y - a d j u s t e d  l i f e 
expectancy: a new tool to inform recommendations for optimal 
screening strategies. Ann Intern Med.2013;159(10):667-676. 
doi:10.7326/0003-4819-159-10-201311190-00005

65. Sammon JD, Abdollah F, D’Amico A, Gettman M, Haese A, Suardi N, et 
al. Predicting life expectancy in men diagnosed with prostate cancer. 
Eur Urol.2015;68(5):756-765. doi:10.1016/j.eururo.2015.03.020

66. Altok M, Menon A, Aly A, White T, Gaybriella J, Xu B, et al. 
Pd15-09 [Abstract] Updated outcomes for active sur veillance 
recommended to all small renal mass patients lacking progression 
criteria for intervention. J Urol.2022;207(Suppl 5):e266. doi:10.1097/
JU.0000000000002547.09

67. Danzig MR, Ghandour RA, Chang P, et al. Active surveillance is superior 
to radical nephrectomy and equivalent to partial nephrectomy for 
preserving renal function in patients with small renal masses: results 
from the DISSRM Registry. J Urol.2015;194(4):903-909. doi:10.1016/j.
juro.2015.03.093

434 SIUJ  •  Volume 3, Number 6  •  November 2022 SIUJ.ORG

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68. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C yuan. Chronic 
kidney disease and the risks of death, cardiovascular events, and 
hospitalization. N Engl J Med.2004;351(13):1296-1305. doi:10.1056/
NEJMoa041031

69. Rodríguez Faba O, Boissier R, Budde K, Figueiredo A, Fraser Taylor, C, 
Hevia V, et al. European Association of Urology Guidelines on renal 
transplantation: update 2018. Eur Urol Focus.2018;4(2):208-215. 
doi:10.1016/j.euf.2018.07.014

70. Rebez G, Pavan N, Mir MC. Available active surveillance follow-
up protocols for small renal mass: a systematic review. World J 
Urol.2021;39(8):2875-2882. doi:10.1007/s00345-020-03581-6

71. Marconi L, Dabestani S, Lam TB, Hofmann F, Stewart F, Norrie J, 
et al. Systematic review and meta-analysis of diagnostic accuracy 
of percutaneous renal tumour biopsy. Eur Urol.2016;69(4):660-673. 
doi:10.1016/j.eururo.2015.07.072

72. Patel HD, Johnson MH, Pierorazio PM, Sozio SM, Sharma R, Lyoha 
E, et al. Diagnostic accuracy and risks of biopsy in the diagnosis of a 
renal mass suspicious for localized renal cell carcinoma: systematic 
review of the literature. J Urol.2016;195(5):1340-1347. doi:10.1016/j.
juro.2015.11.029

73. Schiavina R, Borghesi M, Dababneh H, Bianchi L, Longhi B, Diazzi D, et 
al. Small renal masses managed with active surveillance: predictors 
of tumor growth rate after long-term follow-up. Clin Genitourin 
Cancer.2015;13(2):e87-e92. doi:10.1016/j.clgc.2014.08.006

74. Ajami T, Sebastia C, Corominas D, Ribal MJ, Nicolau C, Alcaraz A, et al. 
Clinical and radiological findings for small renal masses under active 
surveillance. Urol Oncol.2021;39(8):499.e9-499.e14. doi:10.1016/j.
urolonc.2021.04.010

75. Whelan EA, Mason RJ, Himmelman JG, Matheson K, Rendon RA. 
Extended duration of active surveillance of small renal masses: a 
prospective cohort study. J Urol.2019;202(1):57-61. doi:10.1097/
JU.0000000000000075

76. Bertelli E, Palombella A, Sessa F, Baldi I, Morelli N, Verna S, et al. 
Contrast-enhanced ultrasound (CEUS) imaging for active surveillance 
of small renal masses. World J Urol.2021;39(8):2853-2860. doi:10.1007/
s00345-021-03589-6

77. Dorin R, Jackson M, Cusano A, Haddock P, Kiziloz H, Meraney A, et 
al. Active surveillance of renal masses: an analysis of growth kinetics 
and clinical outcomes stratified by radiological characteristics at 
diagnosis. Int Braz J Urol.2014;40(5):627-636. doi:10.1590/S1677-
5538.IBJU.2014.05.07

78. Gupta M, Alam R, Patel HD, Semerjian A, Gorin MA, Johnson MH, et al. 
Use of delayed intervention for small renal masses initially managed 
with active surveillance. Urol Oncol.2019;37(1):18-25. doi:10.1016/j.
urolonc.2018.10.001

79. Paterson C, Yew-Fung C, Sweeney C, Szewczyk-Bieda M, Lang S, Nabi 
G. Predictors of growth kinetics and outcomes in small renal masses 
(SRM ≤4 cm in size): Tayside Active Surveillance Cohort (TASC) Study. 
Eur J Surg Oncol.2017;43(8):1589-1597. doi:10.1016/j.ejso.2017.03.006

80. Rasmussen RG, Xi Y, Sibley RC, Lee C, Cadeddu JA, Pedrosa I. 
Association of clear cell likelihood score on MRI and growth kinetics 
of small solid renal masses on active sur veillance. AJR Am J 
Roentgenol.2021 July 21.ePub. doi:10.2214/AJR.21.25979

81. Brunocilla E, Borghesi M, Schiavina R, Mora LD, Dababneh H, La 
Manna G, et al. Small renal masses initially managed using active 
surveillance: results from a retrospective study with long-term 
follow-up. Clin Genitourin Cancer.2014;12(3):178-181. doi:10.1016/j.
clgc.2013.11.011

82. Mason RJ, Abdolell M, Trottier G, Pringle C, Lawen JG, Bell DG, et al. 
Growth kinetics of renal masses: analysis of a prospective cohort of 
patients undergoing active surveillance. Eur Urol.2011;59(5):863-867. 
doi:10.1016/j.eururo.2011.02.023

83. Kato M, Suzuki T, Suzuki Y, Terasawa Y, Sasano H, Arai Y. Natural history 
of small renal cell carcinoma: evaluation of growth rate, histological 
grade, cell proliferation and apoptosis. J Urol.2004;172(3):863-866. 
doi:10.1097/01.ju.0000136315.80057.99

84. Lee SW, Sung HH, Jeon HG, Jeong BC, Jeon SS, Lee HM, et al. Size and 
volumetric growth kinetics of renal masses in patients with renal cell 
carcinoma. Urology.2016;90:119-124. doi:10.1016/j.urology.2015.10.051

85. Li Z, Zhang J, Zhang L, Yao L, Zhang C, He Z, et al. Natural history 
and growth kinetics of clear cell renal cell carcinoma in sporadic and 
von Hippel-Lindau disease. Transl Androl Urol.2021;10(3):1064-1070. 
doi:10.21037/tau-20-1271

86. Zhang L, Yin W, Yao L, Li X, Fang D, Ren D, et al. Growth pattern 
of clear cell renal cell carcinoma in patients with delayed surgical 
inter vention: fast grow th rate correlates with high grade and 
may result in poor prognosis. Biomed Res Int.2015;2015:598134. 
doi:10.1155/2015/598134

87. Jewett MAS, Rendon R, Lacombe L, Karakiewicz PI, Tanguay S, 
Kassouf W, et al. Canadian guidelines for the management of the small 
renal mass (SRM). Can Urol Assoc J.2015;9(5-6):160-163. doi:10.5489/
cuaj.2969

88. Crispen PL, Viterbo R, Boorjian SA, Greenberg RE, Chen DYT, Uzzo 
RG. Natural history, growth kinetics and outcomes of untreated 
clinically localized renal tumors under active sur veillance. 
Cancer.2009;115(13):2844-2852. doi:10.1002/cncr.24338

89. Parker PA, Alba F, Fellman B, Urbauer DL, Li Y, Karam JA, et al. 
Illness uncertainty and quality of life of patients with small renal 
tumors undergoing watchful waiting: a 2-year prospective study. Eur 
Urol.2013;63(6):1122-1127. doi:10.1016/j.eururo.2013.01.034

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90. O’Connor KM, Davis N, Lennon GM, Quinlan DM, Mulvin DW. Can 
we avoid surgery in elderly patients with renal masses by using 
the Charlson comorbidity index? BJU Int.2009;103(11):1492-1495. 
doi:10.1111/j.1464-410X.2008.08275.x

91. Campi R, Sessa F, Corti F, Carrion DM, Mari A, Amparore D, et al. 
Triggers for delayed intervention in patients with small renal masses 
undergoing active surveillance: a systematic review. Minerva Urol 
Nefrol.2020;72(4):389-407. doi:10.23736/S0393-2249.20.03870-9

92. Suss NR, Bruha MJ, Monaghan TF, Robins D, Flores V, Agudelo CW, 
et al. Assessing the role of race in pathological upstaging of renal 
cell carcinoma: results from the National Cancer Database. Int J Clin 
Pract.2021;75(4):e13818. doi:10.1111/ijcp.13818

93. Chevinsky M, Imnadze M, Sankin A, Winer A, Mano R, Jakubowski C, 
et al. Pathological stage T3a significantly increases disease recurrence 
across all tumor sizes in renal cell carcinoma. J Urol.2015;194(2):310-
315. doi:10.1016/j.juro.2015.02.013

94. Crispen PL, Viterbo R, Fox EB, Greenberg RE, Chen DYT, Uzzo RG. 
Delayed intervention of sporadic renal masses undergoing active 
surveillance. Cancer.2008;112(5):1051-1057. doi:10.1002/cncr.23268

95. Rais-Bahrami S, Guzzo TJ, Jarrett T W, Kavoussi LR, Allaf ME. 
Incidentally discovered renal masses: oncological and perioperative 
outcomes in patients with delayed surgical inter vention. BJU 
Int.2009;103(10):1355-1358. doi:10.1111/j.1464-410X.2008.08242.x

96. Syed JS, Nawaf CB, Rosoff J, Bryson C, Nguyen KA, Suarez-Sarmiento, 
et al. Adverse pathologic characteristics in the small renal mass: 
implications for active surveillance. Can J Urol.2017;24(2):8759-8764.  

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