open access: Nature Reviews: Key Advances in Medicine

P = 0.03). When the analysis was limited to
patients with histologically confirmed renal
cell carcinoma, these differences in overall
survival were less pronounced.
The findings of this study must be placed
in context of its limitations. Designed to
recruit 1,300 patients, the trial was closed
early due to poor accrual, and did not
achieve the target sample size chosen to
identify a 3% difference in 5-year survival.
In addition, there were differences
in baseline comorbidities and considerable
crossover between treatment arms (5.6%
of patients randomized to radical nephrectomy
underwent partial neph rectomy,
and 14.6% of patients randomized to partial
nephrectomy underwent radical nephrectomy),
which may have influenced the
reported survival outcomes. Despite these
limitations, the findings raise important
questions regarding the relative contributions
of preserved renal function and competing
risks from pre-existing comorbidities
to overall survival following surgical resection
for localized renal tumors. Although
these results are thought-provoking, further
study is necessary to determine which
patients stand to benefit the most from
nephron-sparing surgery.
The benefit of renal function preservation
in nephron-sparing surgery must
be weighed against the increased risk of
postoperative complications compared
with radical nephrectomy. 2 However, a
lack of standardized reporting methods
has resulted in a body of literature with
limited generalizability that is challenging
to interpret. In 2011, investigators at
Fox Chase Cancer Center attempted to
address these issues by rigorously evaluating
the complica tions associated with
partial neph rectomy in their institutional
database 4 using the Clavien-Dindo
classifica tion system (CCS). 5 Aiming to
provide a benchmark for comparative
studies between institutions, patients were
stratified using the nephrometry scoring
system 6 to investigate the relationship
between tumor complexity (low complexity
score 4–6; intermediate complexity score
7–9; high complexity score 10–12) and risk
of postoperative complications. The study
cohort consisted of 390 patients with available
imaging data for review, who underwent
partial neph rectomy between 2007
and 2010; 109 (28%), 217 (55.6%), and
64 (16.4%) patients underwent nephron-
sparing surgery for low, intermediate, and
high complexity lesions, respectively. The
overall proportion of patients incurring
minor (CCS I–II) and major (CCS III–V)
complications were 26.7% and 11.5%,
respectively. No significant differences were
observed in minor complications between
complexity groups, but patients with highly
complex lesions were more likely to develop
a major complication requiring secondary
intervention than intermediate and low
complexity tumors (22% versus 11% versus
6%; P = 0.001). Controlling for demographic
and clinical characteristics, patients with
highly complex renal tumors were 5.4 times
(95% CI 1.2–24.2) more likely to sustain a
major complication compared to those with
low complexity lesions. Although this study
was limited by its retrospective methodology
and lack of external validation, these
findings highlight two important points: the
rigorous reporting of complications using
standardized reporting methodology is
essential for comparing outcomes between
institutions, and the benefit of nephron
preserva tion in highly complex tumors
comes with the attendant risk (>20%) of a
major post operative complication.
Recent evidence suggests that a substantial
proportion of the rapidly rising
number of incidentally diagnosed small
renal masses represents indolent disease
Key advances
■ In a recent phase III randomized trial, 3
partial nephrectomy demonstrated
equivalent cancer-specific survival to
radical surgery for tumors ≤5 cm, but did
not demonstrate the expected overall
survival benefit
■ The benefit of nephron preservation
in highly complex tumors comes with
the attendant risk (>20%) of a major
postoperative complication 4
■ A large proportion of small renal masses
under observation grow slowly, and
the short-term risks of progression or
metastasis under active surveillance are
low 9
UROLOGY
that may not require treatment. 7 As a
result, much attention has been directed
towards describing the natural history of
untreated renal tumors in an effort to identify
which lesions are safe to observe and
which require early definitive intervention. 8
In 2011, Jewett et al. 9 reported the results
of a multicenter prospective phase II trial
investigating the growth kinetics and progression
rates of 209 incidentally diagnosed
cT1a lesions under observation in
patients deemed unfit for surgery owing
to advanced age, comorbidity, or refusal
of other treatment. 9 In this cohort of 178
patients (mean age 73 years, mean tumor
size 2.3 cm), the authors defined tumor progression
as growth to ≥4 cm, tumor volume
doubling time ≤12 months, or progression
to metastatic disease. Notably, 99 patients
(56%) underwent renal biopsy and 127
patients (151 masses) were followed up for
>12 months (mean 28 months). Important
study findings include an average growth
rate of 0.13 cm per year, documented progression
(as defined above) in 27 patients
(15%), and only two patients (1.1%) developing
evidence of metastatic disease.
Furthermore, there was no difference in
growth rate between biopsy-proven malignant
and benign disease (0.14 cm per year
versus 0.17 cm per year; P = 0.8), and 36% of
biopsy-proven renal cell carcinomas showed
either no evidence of growth or a decrease
in size. Although limited by lack of central
pathology review, elevated nondiagnostic
biopsy rate (33%), and short duration of
follow-up, this study should be commended
for its rigorous eligibility criteria, use of protocol
renal mass biopsy, and strict definition
of tumor progression. These findings add
significantly to the growing body of literature
documenting that a large proportion of
small renal masses under observation grow
slowly, and that short-term risks of progression
or metastasis under active surveillance
are low. 8,10
In the absence of level 1 evidence, physicians
are increasingly challenged to manage
risk on a patient by patient basis. Although
the list of unanswered questions remains
long, the studies described above each
provide evidence to improve risk communication
and enable tradeoff decisions
when counseling patients diagnosed with
localized renal tumors. Until the ability to
match treatment to tumor biology has been
achieved, urologists must continue to vigilantly
evaluate and challenge contemporary
management strategies, objectify tradeoff
risks, and individualize treatment strategies.
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