and ALT than metastases in other organs. It is expected that
the correlation between the presence, number, and volume of
metastasis and De Ritis ratio in mRCC patients will be clari-
ﬁed in the near future. Another point of interest regarding the
De Ritis ratio in mRCC is whether it is clinically useful as a
biomarker for representing the effectiveness of systemic ther-
apy. To clarify this point, the impact of the change in De
Ritis ratio during treatment on predicting its outcome should
be assessed. For instance, in C-reactive protein, a change in
its serum level is associated with the effectiveness of sys-
temic therapy, as well as the progression of a disease or prog-
Further studies are expected to assess the impact of
the kinetics of the De Ritis ratio in clinical practice for
patients with mRCC.
and Akio Matsubara
Department of Urology, Graduate School of Biomedical and
Health Science, Hiroshima University, Hiroshima, Japan
Conﬂict of interest
1 Kang M, Yu J, Sung HH et al. Prognostic impact of the pretreatment aspartate
transaminase/alanine transaminase ratio in patients treated with ﬁrst-line sys-
temic tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma. Int.
J. Urol. 2018; 25: 596–603.
2 Teishima J, Kobatake K, Hayashi T et al. Prognostic signiﬁcance of C-reactive
protein in patients with intermediate-risk metastatic renal cell carcinoma treated
with molecular targeted therapy. Oncol. Lett. 2014; 8: 881–5.
3 Tanaka N, Mizuno R, Yasumizu Y et al. Prognostic value of neutrophil-to-
lymphocyte ratio in patients with metastatic renal cell carcinoma treated with
ﬁrst-line and subsequent second-line targeted therapy: a proposal of the modi-
ﬁed-IMDC risk model. Urol. Oncol. 2017; 35: 39.e19–28.
4 McKay RR, Kroeger N, Xie W et al. Impact of bone and liver metastases on
patients with renal cell carcinoma treated with targeted therapy. Eur. Urol.
2014; 65: 577–84.
5 Teishima J, Kobatake K, Kitano H et al. The impact of change in serum C-reac-
tive protein level on the prediction of effects of molecular targeted therapy in
patients with metastatic renal cell carcinoma. BJU Int. 2016; 117(6B): E67–74.
Editorial Comment from Dr Yuasa to Prognostic impact of the pretreatment aspartate
transaminase/alanine transaminase ratio in patients treated with ﬁrst-line systemic
tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma
A better understanding of molecular biology has led to major
breakthroughs in medical treatment for patients with metastatic
renal cell cancer (RCC). Vascular endothelial growth factor,
platelet-derived growth factor and mechanistic target of rapa-
mycin signaling pathways have been recognized as rational
targets for targeted therapy.
Furthermore, nivolumab (Optivo;
Ono Pharmaceutical, Osaka, Japan; Bristol-Myers Squibb,
Tokyo, Japan), which selectively inhibits the programmed
death 1 immune checkpoint molecule, was launched in 2016
and has been rapidly introduced into clinical practice for meta-
static RCC in Japan.
As various treatment options become
available, identiﬁcation of biomarkers to predict therapy
response and side-effects is urgently required.
Liver enzymes, which include the aminotransaminases
aspartate transaminase (AST) and alanine transaminase
(ALT), are released from liver cells into the blood. AST and
ALT levels are commonly requested as a part of liver func-
tion tests. Recently, the AST-to-ALT ratio (De Ritis ratio)
was shown to be an independent predictor of patient survival
in metastatic RCC. Ishihara et al. reported that the preopera-
tive De Ritis ratio is an independent predictive biomarker for
both cancer-speciﬁc survival (CSS) and overall survival (OS)
in patients with metastatic RCC who undergo cytoreductive
In this issue of the International Journal of Urology, Kang
et al. showed the usefulness of the De Ritis ratio as a
predictive marker in metastatic RCC patients who received
ﬁrst-line systemic targeted therapy.
Patients with a higher
pretreatment De Ritis ratio (≥1.2) had worse CSS and OS
outcomes, compared with those with a lower De Ritis ratio
(<1.2). A higher De Ritis ratio (≥1.2) was identiﬁed as an
independent predictor of both CSS (hazard ratio 1.49) and
OS outcomes (hazard ratio 1.67). Additionally, a potential
advantage of the De Ritis ratio was suggested in this study.
Clinical factors in metastatic RCC patients already include
two well-known criteria: the Memorial Sloan Kettering Can-
cer Center criteria and the International Metastatic RCC Data-
base Consortium criteria.
A potential weak point of these
criteria is that a relatively high number of patients are classi-
ﬁed into the intermediate-risk group. The application of the
De Ritis ratio, using stratiﬁcation by above or below 1.2
(AST/ALT), resulted in populations with distinctly separate
CSS and OS outcomes in the intermediate-risk group,
although no signiﬁcant effect was found on survival outcome
among the patients in the favorable and poor risk groups.
The AST and ALT levels can be easily evaluated and moni-
tored routinely without invasive procedures. This novel and
simple biomarker can be a useful predictor of the prognosis
of patients with metastatic RCC in clinical practice.
Department of Urology, Cancer Institute Hospital, Japanese
Foundation for Cancer Research, Ariake, Tokyo, Japan
© 2018 The Japanese Urological Association
M KANG ET AL.