G. Bratslavsky

H Miyake

H Wunderlich

K Junker

M Sorbellini

M. Sorbellini

ML Blute

O Yossepowitch

S Sudarshan

T Kinouchi

WC Huang

English

PubMed

Springer - Publisher Connector

EDITORIAL
Renal Cell Carcinoma and Prognostic Factors Predictive
of Survival
M. Sorbellini, MD and G. Bratslavsky, MD
Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
We congratulate Haferkamp et al.1 for their work trying
to identify prognostic factors predictive of survival for
patients with renal cell carcinoma (RCC) who undergo
nephron-sparing surgery for imperative indications.
Although in the past decade, there has been a trend to move
from radical nephrectomy to nephron preservation, many
renal units are still lost unnecessarily. Identifying those
patients at a higher risk for metastatic disease and those
who are likely to fail local therapy is of paramount
importance.
In the present study, the authors excluded patients with
von Hippel-Lindau (VHL) syndrome, because these
patients are prone to develop bilateral multifocal recurrent
clear cell renal carcinomas. However, the reader should be
aware that there are other hereditary syndromes besides
VHL that predispose to the development of bilateral and/or
multifocal renal cell carcinoma. These include patients
with hereditary papillary renal carcinoma (HPRC) who
develop bilateral papillary type 1 RCC, hereditary leio-
myomatosis RCC (HLRCC) patients who tend to form
aggressive papillary type 2 RCC, Birt-Hogg-Dube’ (BHD)
patients who may develop a whole spectrum of tumors
from benign oncocytomas to chromophobe RCC to
aggressive clear cell RCC, and several other less-recog-
nized syndromes, such as tuberous sclerosis and succinate-
dehydrogenase-B deficiency.2 The above-mentioned syn-
dromes may have multifocal RCC as a sole manifestation
or as a constituent of a complex multiorgan involvement.
Therefore, caution should be used in evaluating a study that
excludes only VHL patients but not other hereditary forms
of RCC. Additionally, there is a great variability of
aggressiveness of lesions in patients with multifocal RCC.
Unfortunately, the authors fail to delineate the type of
patients who fit in the category of ‘‘imperative indica-
tions.’’ Were there patients with solitary renal units due to
contralateral nephrectomy or congenital absence of the
contralateral kidney? If the contralateral kidney was lost
due to cancer, which pathological variables were analyzed?
Predicting cancer-specific survival from resection of a T1
renal mass from a solitary kidney may not be driving the
oncologic outcome if the same patient had a contralateral
nephrectomy for a T3 disease. Because 50% of the cohort
had bilateral disease, pathological information about con-
tralateral kidney would be of great value and could provide
additional predictors of poor outcome. Perhaps, a surpris-
ing finding of similar cancer-specific survival between T1,
T2, and T3 groups may be explained by the confounding
effects of contralateral pathology.
The authors also evaluated the effect of multifocality in
their analysis. It has been shown that multifocal RCC is
much more prevalent than originally believed, and ranges
from 5–25% in the literature.3,4 The problem with the study
of multifocal RCC is our current inability to determine
whether a second renal tumor in the same or the contra-
lateral kidney is indeed part of multifocal disease or simply
a recurrence or metastasis from a previously operated
tumor. Without a specific genetic study designed to eval-
uate the clonal origin of each mass found, it is impossible
to determine whether patients have multifocal, recurrent, or
metastatic disease.5–7 Had recurrences been counted as
multifocality, the assignment of patients to the different
groups in the study may have affected the statistical anal-
ysis. The opposite also could be true. Because
approximately 20% of lesions are missed by current
imaging techniques both preoperatively and intraopera-
tively, patients assigned to the unifocal group may have
actually had multifocal disease. This would have influ-
enced the assignment of patients into various groups being
analyzed and ultimately accounted for the lack of statistical
 Society of Surgical Oncology 2009
Published Online: 12 November 2009
G. Bratslavsky, MD
e-mail: bratslag@mail.nih.gov
Ann Surg Oncol (2010) 17:362–363
DOI 10.1245/s10434-009-0817-6
significance between unifocal vs. multifocal groups and
unilateral vs. bilateral groups.
Although the present study evaluates patients spanning
almost three decades, one of the major drawbacks is the
fact that it may not have enough events to achieve statis-
tical power.1 This is evident by the fact that well-known
prognostic factors for cancer-specific survival (CSS), such
as clinical stage (Tables 2, 3, 4), did not achieve statistical
significance in this study. Therefore, it is likely that a type
II error is present in evaluating the variables responsible for
CSS. Furthermore, the authors attempted to perform mul-
tivariate analyses of variables that were not significant on
univariate analysis and the statistical validity of this anal-
ysis is questionable.
Finally, the authors found a ‘‘tendency’’ toward unfa-
vorable prognosis in the case of positive surgical margins.
Had there been more events, this tendency may have
become statistically significant or completely disappeared.
Moreover, the authors suggest doing everything in one’s
hands to avoid having positive surgical margins, including
radical nephrectomy. Although we also strongly advocate
appropriate surgery with negative surgical margins, the
reader should be aware of recent data showing that posi-
tive surgical margins do not jeopardize survival outcomes
in patients who undergo nephron-sparing surgery.8 In
addition, loss of nephrons and its consequent renal
insufficiency subjects patients to an increased risk for
cardiovascular disease and death.9,10 Thus, we encourage
surgeons to attempt nephron-sparing techniques whenever
feasible.
ACKNOWLEDGEMENT This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
REFERENCES
1. Haferkamp A, Kurosch M, Pritsch M, et al. Prognostic factors
influencing long-term survival of patients undergoing nephron-
sparing surgery for nonmetastatic renal-cell carcinoma (RCC)
with imperative indications. Ann Surg Oncol. 2010. doi:10.1245/
s10434-009-0812-y
2. Sudarshan S, Linehan WM. Genetic basis of cancer of the kidney.
Semin Oncol. 2006;33(5):544–51
3. Wunderlich H, Schlichter A, Zermann D, et al. Multifocality in
renal cell carcinoma: a bilateral event? Urol Int. 1999;63(3):160–3.
4. Kinouchi T, Mano M, Saiki S, et al. Incidence rate of satellite
tumors in renal cell carcinoma. Cancer. 1999;86(11):2331–6.
5. Miyake H, Nakamura H, Hara I, et al. Multifocal renal cell car-
cinoma: evidence for a common clonal origin. Clin Cancer Res.
1998;4(10):2491–4.
6. Junker K, Thrum K, Schlichter A, et al. Clonal origin of multi-
focal renal cell carcinoma as determined by microsatellite
analysis. J Urol. 2002;168(6):2632–6.
7. Blute ML, Itano NB, Cheville JC, et al. The effect of bilaterality,
pathological features and surgical outcome in nonhereditary renal
cell carcinoma. J Urol. 2003;169(4):1276–81.
8. Yossepowitch O, Thompson RH, Leibovich BC, et al. Positive
surgical margins at partial nephrectomy: predictors and onco-
logical outcomes. J Urol. 2008;179(6):2158–63.
9. Huang WC, Elkin EB, Levey AS, et al. Partial nephrectomy
versus radical nephrectomy in patients with small renal tumors:
is there a difference in mortality and cardiovascular outcomes?
J Urol. 2009;181(1):55–62.
10. Sorbellini M, Kattan MW, Snyder ME, et al. Prognostic nomo-
gram for renal insufficiency after radical or partial nephrectomy.
J Urol. 2006;176(2):472–6.
Renal Cell Carcinoma and Prognostic Factors 363


Renal Cell Carcinoma and Prognostic Factors Predictive of Survival

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Clonal origin of multifocal renal cell carcinoma as determined by microsatellite analysis.

Genetic basis of cancer of the kidney. Semin Oncol.

Incidence rate of satellite tumors in renal cell carcinoma.

Multifocal renal cell carcinoma: evidence for a common clonal origin. Clin Cancer Res.

Partial nephrectomy versus radical nephrectomy in patients with small renal tumors: is there a difference in mortality and cardiovascular outcomes?

Positive surgical margins at partial nephrectomy: predictors and oncological outcomes.

Prognostic factors inﬂuencing long-term survival of patients undergoing nephronsparing surgery for nonmetastatic renal-cell carcinoma (RCC) with imperative indications. Ann Surg Oncol.

Prognostic nomogram for renal insufﬁciency after radical or partial nephrectomy.

The effect of bilaterality, pathological features and surgical outcome in nonhereditary renal cell carcinoma.

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Renal Cell Carcinoma and Prognostic Factors Predictive of Survival

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