Kidney Cancer Journal 111
with unfavorable pathology.24 While these hypothesisgenerating
data warrant validation, the number of positive
growth periods may be a new reasonable parameter
for malignant potential in patients undergoing AS for
SRMs and could be utilized to initiate delayed intervention.
Lastly, it is essential to recognize that the growth
rate cutoff of >0.5 cm/year was based on retrospective
data; as such, a more relevant biological threshold may
exist and differ than this. Alternatively, a growth rate
threshold could be used to trigger a biopsy, biomarker, or
novel imaging modality parameter, rather than surgical
intervention.
Renal Mass Biopsy
The role of percutaneous renal mass biopsy (RMB) in AS
patients with SRMs remains debatable. While RMB exhibits
excellent positive performance characteristics (sensitivity,
specificity, and positive predictive value above
90%)25,26, it is not uniformly performed in patients enrolling
in AS programs. Its clinical utility has been limited
by concerns about its safety and the lack of perceived impact
on clinical management in most cases given its inability
to reliably detect high-grade disease due to intra-
tumoral grade heterogeneity (40-60%), its significant
non-diagnostic rate (14%), and its poor negative predictive
value (68.5%).27-29
Despite the general belief in potential morbidity, RMB
has been demonstrated to be a safe procedure with exceedingly
low risk of serious complications – less than 1%
of patients develop serious bleeding requiring blood
transfusion and only 5% experience a hematoma. Moreover,
tumor seeding does not occur with modern techniques
of biopsy.26 RMB has also been shown to alleviate
disease-related anxiety and depression in select patients.
In a prospective DISSRM analysis of quality of life using
the SF12 questionnaire, a significant improvement (p =
0.04) in the mental component score of AS patients was
noted after RMB.30 It is important to emphasize, however,
that overall quality of life is primarily driven by perceived
differences in physical health and not mental health domains30;
as such, while RMB can promote the emotional
wellbeing of patients with SRMs managed by AS, its impact
on overall quality of life is less profound.
RMB is not a requisite for safe AS. Nevertheless, it can
provide valuable information for patients and providers
when used appropriately. RMB can be offered initially if
surveillance strategies will be tailored to tumor histology
and perceived biology. Given the uncertainties surrounding
a “benign” biopsy and poor grade concordance for
high-grade RCC, we follow a similar surveillance strategy
regardless of RMB histology and therefore recommend
the use of RMB in patients in whom the findings may
alter treatment decision. Baseline risk stratification of patients
based on clinical predictors of metastatic potential
and death of competing causes should ideally dictate
if/when RMB is useful. For example, younger and healthier
patients who can tolerate a minimally-invasive partial
nephrectomy should be alarmed by the significant negative
predictive value and still consider surgery even if
biopsy shows benign or low-grade tumor due to heterogeneity
of SRMs.
On the other hand, elderly patients with multiple comorbidities
and limited life expectancy who are poor surgical
candidates would preferably be better off if managed
with AS regardless of RMB result, especially given the excellent
cancer-specific survival of SRMs mentioned earlier.
Patients in whom the decision to choose AS or surgery is
less clear, or patients in whom the role of nephron-sparing
approaches versus radical nephrectomy is uncertain,
may benefit from RMB and, thus, are the ones in whom
RMB should be performed. Moreover, as reported previously
in this review, RMB may be useful in growing SRMs,
particularly those demonstrating elevated growth rate
within the first year of AS, as a diagnosis of high grade
RCC would prompt timely intervention.
The frequency of RMB in the DISSRM registry has increased
from being done in approximately 5% of patients
per year to 20% in the most recent update.12 As our understanding
of the role of RMB in the management of
SRMs matures and with increasing follow-up in DISSRM,
we expect to see an even greater proportion of patients
electing biopsy.
Active Surveillance and Chest Imaging
Lung metastases are common in patients with RCC.
Given this metastatic potential, yearly chest imaging is
currently widely accepted as standard follow-up for patients
managed by AS for SRMs suspicious for clinically
localized RCC. However, as noted previously in this review,
metastatic progression of SRMs while on AS is significantly
rare.8 Moreover, all patients with progression
to metastatic RCC in the AS literature either had a baseline
tumor diameter of 3 cm or greater, experienced significant
growth of their SRM on surveillance and were
upstaged to cT1b, and/or were lost to follow-up for a significant
period of time.31 As such, routine chest imaging
is unlikely to detect pulmonary metastases in patients
with SRMs that do not progress by size. Yearly chest imaging
can, on the other hand, potentially lead to an increased
rate of incidental findings that are unrelated to
RCC and result in unnecessary and costly work-up for patients
on AS.
An analysis of chest imaging data in the DISSRM registry
was recently performed to support these hypotheses;
while the actual manuscript including the results of that
analysis is currently still under review for publication, a
brief summary of the findings is presented here. The DISSRM
AS protocol recommends chest imaging – either
chest x-ray (CXR) or computed tomography (CT) scan –
at enrollment and annually thereafter.10 Available chest
imaging reports were examined to identify patients with
abnormal findings, and abnormal findings were then determined
to be actionable or non-actionable based on receipt
of further work-up and/or procedures. Of 268 AS
patients included in the analysis, 51 (19%) were found to
have abnormal baseline chest images. Of these 51 initially
abnormal chest imaging reports, 22 (43%) were or eventually
became actionable, and 29 (57%) were non-actionable.
Of the 217 patients with normal baseline chest
images, 23 (11%) showed abnormal findings on subsequent
follow-up chest imaging; abnormal findings were
actionable in 10 (43%) of these 23 patients.
Actionable findings included pulmonary nodule 5
mm (single or multiple) concerning for lung malignancy