EURURO Vol. 71 No. 5

E139 844

Letter to the Editor
Re: Brian I. Rini, Tanya B. Dorff, Paul Elson, et al. Active
Surveillance in Metastatic Renal-cell Carcinoma:
A Prospective, Phase 2 Trial. Lancet Oncol Lancet
2016;17:1317–24
Active Surveillance in Metastatic Renal Cell Carcinoma:
Option or Exception?
The study by Rini and colleagues is the first prospective
observational study of asymptomatic patients with meta-
static renal cell carcinoma (mRCC) who undergo an initial
period of surveillance before starting systemic therapy.
Virtually all the patients (n = 47/48) underwent previous
nephrectomy showing optimal performance status (Kar-
nofsky 90–100 in n = 45/48) and favourable/intermediate
(n = 47/48) International Metastatic Database Consortium
risk score The authors concluded that in this specific
scenario, some mRCC patients might safely undergo
observation before starting targeted therapy.
The study is of outstanding importance, since it confirms
the clinical feeling that a very select cohort of asymptomatic
patients with favourable disease do not show clinical or
radiologic progression in the first months after surgery,
even in the absence of subsequent systemic therapy.
Moreover, these findings are of overwhelming importance
considering the potential toxicity and costs related to
targeted therapy. However, the authors’ postulation that ‘‘in
a subset of patients with mRCC surveillance does not clearly
compromise the benefit of systemic therapy when initiated’’
is still premature.
First, this is not a comparative trial between active
surveillance and immediate systemic therapy. Therefore, it
cannot be determined whether active surveillance is
equally or less effective than an immediate multimodal
approach (surgery + systemic therapy).
Second, the inclusion criteria are too heterogeneous:
although the majority of patients underwent prior nephrec-
tomy, the report has not considered the effect of surgical
debulking and its extent on the natural history of the
disease. Indeed, patients who were included had mainly
lung or lymph node metastases, with most having only one
metastatic organ and a low tumour burden at baselin
In daily clinical practice, these favourable characteristics
frequently allow consideration of the indication, besides
nephrectomy, for upfront surgical metastasectomy or
retroperitoneal lymph node dissection or bone radiation
as well. Although its effect on cancer control is debatable,
this multimodal approach might at least mitigate the extent
of progression and postpone the initiation of systemic
therapy . Although their level of evidence is limited,
previous published data have indeed shown a benefit of
metastasectomy for mRCC patients who have been selected
for favourable characteristics and low metastatic tumour
burden Therefore, it is possible that patients who
might be candidates for surveillance before starting
systemic therapy might be those who receive the greatest
extent of debulking on initial management.
In conclusion, this study does represent an important
milestone in the setting of mRCC management. However,
the dilemma still persists as to whether cancer control is
compromised among patients who undergo an initial period
of observation in comparison to immediate systemic
therapy, and how critical the extent of initial debulking is.
Conflicts of interest: The authors have nothing to disclose.
References
[1] Rini BI, Dorff TB, Elson P, Rodriguez CS, Shepard D. Active surveil-
lance in metastatic renal-cell carcinoma: a prospective, phase
2 trial. Lancet Oncol 2016;17:1317–24.
.
[2] Capitanio U. FRCS PFM. Renal cancer. Lancet 2016;387:894–906.
.
[3] Dabestani S, Marconi L, Hofmann F, Stewart F. Local treatments for
metastases of renal cell carcinoma: a systematic review. Lancet
2014;15:e549–61.
.
[4] Zaid HB, Parker WP, Safdar NS, et al. Outcomes following complete
surgical metastasectomy for patients with metastatic renal cell
carcinoma: a systematic review and meta-analysis. J Urol 2017;
197:44–9. .
[5] Capitanio U, Abdollah F, Matloob R, et al. Effect of number and
location of distant metastases on renal cell carcinoma mortality in
candidates for cytoreductive nephrectomy: implications for multi-
modal therapy. Int J Urol 2013;20:572–9.
ava ilable at
journal homepage:
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.