Kidney Cancer Journal 57
sition the role of CN within the framework of a stepwise
approach, Choueiri and Motzer24 presented an algorithm
in their paper on the use of systemic therapy. Published
in 2017 this report touts the advantages offered by combinatorial
strategies, including the use of immunotherapy
combinations. Nevertheless, the algorithm favors
consideration of CN as the initial step in management.
Other recent papers have more directly addressed the
utilization of CN as they evaluated utilization rates and
examined the survival benefit of CN compared with non-
CN patients treated with targeted therapy. Using the National
Cancer Data Base to identify patients with mRCC
treated in the targeted therapy era, Hanna et al3 unpacked
data from information gathered on 15,390 patients. Highlights
from their results:
• As might be expected, patients who were younger, privately
insured, treated at an academic center, and had
a lower tumor stage and cN0 disease were more likely
to undergo CN.
• CN use was stable between 2006 and 2012; performance
was relatively seldom in approximately 3 of 10
patients with mRCC treated with targeted therapy.
• Significantly, the median OS of CN vs non-CN patients
was 17.1 vs 7.7 months.
• In an adjustment analysis to consider other covariates,
CN patients had a lower risk of any death (hazard
ratio, 0.45, P<.001).
Lower Rate of CN Is Worrisome
In parsing their data, and observing some distinctions between
their results and other papers, Hanna et al3 suggest
some disturbing trends in utilization of CN. One observation
was that the overall rate of CN observed in their
study (approximately 30%) was lower than the overall
rate reported from centers of excellence (approximately
58% to 85%). If one extrapolates the data further, there is
additional reason for concern, especially because the
NCDB data are based on a sample of patients treated by
cancer-accredited programs with a minimum threshold
of 100 cases per year. The worrisome aspect, the authors
suggest, is due to the disparity in rates that may be inferred
from the academic setting to what is being utilized
in the general population. It may be that the underuse of
CN in the community setting may be even greater than
ment and accrual was slow over an 8-year interval but
nonetheless, there was statistically significant improvement in
overall clinical benefit in patients who did not undergo
nephrectomy. This is the second of two highly anticipated
randomize controlled trials of timing of cytoreductive
nephrectomy (CN) in the targeted therapy (TT) era.4 Both
study trials failed to achieve original estimated enrollment.
This is mainly due to patient non-compliance to randomization.
5
These randomized control trials have proven to be in contrast
to large data sets that seem to demonstrate an overall
survival benefit to multimodal therapy. For instance, in a recent
national cancer data base study of over 15,000 patients.,
more patients completed multimodal therapy with initial CN
and achieved significantly improved overall survival compared
with patients who had initial TT.6 However, patients
who underwent initial targeted therapy and subsequent cytoreductive
nephrectomy appeared to have comparable
overall survival outcomes. The current CARMENA trial is remarkable
for inclusion of the highest risk groups, i.e. 55% Memorial
Sloan Kettering (MSK) intermediate risk and 44% MSK
poor risk. In addition, 70% of the nephrectomy/sunitinib
group was tumor stage T-3 or T-4 vs 51% of the sunitinib alone
group. In addition, 30% of the nephrectomy/sunitinib group
had cN+ designation versus only 19% of the sunitinib alone
group. MSKCC poor risk grouping, clinical T3 or 4 disease and
evidence of lymphadenopathy are all identified as poor selection
factors for patients to undergo CN.
According to the MD Anderson Cancer Center, low albumin,
high lactate dehydrogenase, tumor stage-clinical T3 or
T4, nodal stage cN+, symptoms at presentation, and liver
metastasis aide in identifying patients that will profit the most
from cytoreductive nephrectomy.7 Specifically, patients with
three or fewer adverse prognostic factors based on each of
these stratifications are likely to draw greater benefit from cytoreductive
nephrectomy. The indication for surgical treatment
in metastatic renal cell cancer remains a difficult
decision. The potential for survival benefit must be measured
against the morbidity of an aggressive surgical procedure. It
is clear that metastatic risk group stratification is important
and close attention to adverse prognostic findings would
seem to mean that patients with poor risk features should not
receive initial cytoreductive nephrectomy. Patients with excellent
performance and low volume metastasis remain candidates
for CN followed by surveillance, TT or judicious consideration
for metastasectomy.
References
1. You D, Jeong IG, Ahn JH, et al. The value of cytoreductive nephrectomy for
metastatic renal cell carcinoma in the era of targeted therapy. J Urol.
2011;185:54-59.
2. Choueiri TK, Xie W, Kollmansberger C, et al. The impact of cytoreductive
nephrectomy on survival of patientswith metastatic renal cell carcinoma receiving
vascular endothelial growth factor targeted therapy. J Urol.
2011;185:60-66.
3. Méjean AR, Ravaud S, Thezenas SC, et al. Sunitinib Alone or after Nephrectomy
in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018 Jun 3. doi:10.
1056/NEJmoa1803675.
4. Bex A, Mulders P, Jewett MAS, et al. Immediate versus deferred cytoreductive
nephrectomy (CN) in patients with synchronous metastatic renal cell
carcinoma mRCC) receiving Sunitinib (EORTV 30073 SURTIME). Eur Urol. Suppl
2018;17L2):e1-e2. Abstract.
5. Steward GD, Aitchison J, Bex A, et al. Cytoreductive Nephrectomy in the
Tyrosine Kinase Inhibitor Era: A Question That May Never Be Answered. European
Urol. 2017;71:845-7. doi:10.1016/j.eururo.2016. 10.029.
6. Bhindi B, Habermann EB, Mason RJ, et al. Comparative Survival Following
Initial Cytoreductive Nephrectomy Versus Initial Targeted Therapy for
Metastatic Renal Cell Carcinoma. J Urol. 2018. Doi:10.1016/j. juro.2018. 03.077.
7. Culp SH, Tannir NM, Abel EJ, et al. Can we better select patients with
metastatic renal cell carcinoma for cytoreductive nephrectomy? Cancer.
2010;116:3378-88. doi:10.1002/cncr.25046