Essential Peer-Reviewed Reading in Kidney Cancer
The peer-reviewed articles summarized in this section were selected by the
Editor-in-Chief, Robert A. Figlin, MD, for their timeliness, importance, relevance,
and potential impact on clinical practice or translational research.
Clinicopathologic features associated with survival
after cytoreductive nephrectomy for nonclear cell
renal cell carcinoma. Silagy AW, Flynn J, Mano R, et
al. Urol Oncol. 2019 Sep 12. pii: S1078-1439(19)30287-
X. doi: 10.1016/j.urolonc.2019.07.011. Epub ahead of
print
Summary: Resultd are based on a prospectively maintained
database for patients who underwent CN for
nccRCC between 1989 and 2018. Histology was reviewed
by an expert genitourinary pathologist, and
nccRCC tumors were subdivided into papillary, unclassified,
chromophobe, and other histology. Baseline
clinicopathology, treatments, and survival outcomes
were recorded. Preoperative hematological parameters
including the neutrophil-to-lymphocyte ratio (NLR)
were analyzed. Significant univariate predictors of OS
were tested in a multivariate model. There were 100
nccRCC patients treated with CN. Median age was 61
years and 65% were male. There were 79 patient deaths
with a median OS of 13.7 months (10.8-27.2).
Estimated 2- and 5-year survival was 40.1% and 12.2%,
respectively. Median follow-up of survivors was 13
months. On multivariate analysis, increasing NLR
(hazard ratio HR 1.27; 95% confidence interval CI
1.14-1.40, P < 0.001) and sarcomatoid features (HR
2.18; 95% CI 1.19-3.97, P = 0.014) conferred worse OS
and the presence of papillary features were a favorable
prognostic feature (HR 0.37; 95% CI 0.21-0.65,
P < 0.001).
Conclusion: OS outcomes in patients with nccRCC
who underwent a CN were consistently modest throughout
the study period. Patients with papillary features
and a lower preoperative NLR may be better candidates
for a CN.
64 Kidney Cancer Journal
The impact of corticosteroid use during anti-PD1
treatment. Pan EY, Merl MY, Lin K et al. J Oncol Pharm
Pract. 2019 Sep 7:1078155219872786. doi: 10.1177/
1078155219872786. Epub ahead of print
Summary: Anti-PD1 therapy has the potential to cause
immune-related adverse events (irAEs), which can be
treated with corticosteroids if severe. The clinical implications
of concomitant immunotherapy and systemic
steroids remain unclear, as short courses of steroids do
not significantly suppress T-cell function. The primary
objective of this study is to determine if the use of
concomitant steroids impacts the efficacy of anti-PD1
therapy. This retrospective, single-center study
reviewed adult patients who received at least four
cycles of nivolumab or pembrolizumab for the treatment
of melanoma, non-small cell lung cancer
(NSCLC), or renal cell carcinoma from November 2014
to February 2016. Patients who received steroids (prednisone
equivalent >10 mg) during anti-PD1 therapy
were divided into two main cohorts based on the duration
of steroid administration of ≤2 weeks or >2 weeks.
Time to disease progression, overall response, and overall
survival were assessed. Twenty-seven of 55 patients
(13 melanoma, 11 NSCLC, 3 renal cell carcinoma)
required steroids during anti-PD1 therapy. In patients
who received steroids, median time to disease progression
was 5.6 months for melanoma, 5.8 for NSCLC,
and 2.0 for renal cell carcinoma. The overall response
rate (ORR) was 3/13 (23%) for melanoma, 6/11 (54%)
for NSCLC, and 1/3 (33%) for renal cell carcinoma.
Median overall survival was 11.9 months for
melanoma, 9.9 for NSCLC, and not reached for renal
cell carcinoma. Thirteen patients who had received
steroids expired; 11 of these patients had received
prednisone >10 mg/day for >2 weeks.
Conclusion: High-dose steroids for long durations
during anti-PD1 therapy may be associated with poorer
survival outcomes.
Angiogenic Factor and Cytokine Analysis among
Patients Treated with Adjuvant VEGFR TKIs in
Resected Renal Cell Carcinoma. Xu W, Puligandla M,
Manola , et al. Clin Cancer Res. 2019 Aug 30. doi:
10.1158/1078-0432.CCR-19-0818. Epub ahead of
print
Summary: The use of VEGFR TKIs for the adjuvant
treatment of renal cell carcinoma (RCC) remains
controversial. This study investigated the effects of
adjuvant VEGFR TKIs on circulating cytokines in the
ECOG-ACRIN 2805 (ASSURE) trial. Patients with
resected high-risk RCC were randomized to sunitinib,
sorafenib, or placebo. Plasma from 413 patients was
analyzed from post-nephrectomy baseline, 4 weeks,
and 6 weeks after treatment initiation. Mixed effects
and Cox proportional hazards models were used to test
for changes in circulating cytokines and associations
between disease-free survival (DFS) and cytokine levels.
VEGF and PlGF increased after 4 weeks on sunitinib
or sorafenib (P < 0.0001 for both) and returned to
baseline at 6 weeks on sunitinib (corresponding to
the break in the sunitinib schedule) but not sorafenib
(which was administered continuously). sFLT-1
decreased after 4 weeks on sunitinib and 6 weeks on
sorafenib (P < 0.0001). sVEGFR-2 decreased after both 4
and 6 weeks of treatment on sunitinib or sorafenib
(P < 0.0001). Patients receiving placebo had no significant
changes in cytokine levels. CXCL10 was elevated
at 4 and 6 weeks on sunitinib and sorafenib but not on
J O U R N A L C L U B
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