the upfront CN group of intermediate-risk mRCC patients
of CARMENA.9 Instead, the median OS of those
receiving nephrectomies in ADAPT was more comparable
to the poor-risk group of patients receiving upfront
CN in CARMENA. It is important to note that this would
be a cross-study comparison with inherent limitations
and that Rocapuldencel-T is different from conventional
ICIs that have been established in the first-line treatment
of mRCC. Nevertheless, ADAPT provides initial glimpses
into the outcomes of mRCC patients receiving nephrectomies
and immunotherapy-based regimens in the more
current era.
Although evidence seeking to address the role of CN
in mRCC in the immunotherapy era is starting to be
published, further investigation in ideally large, prospective
settings are certainly warranted. It is worthwhile to
mention that ongoing phase III studies of CN and ICIbased
regimens in mRCC are evaluating the impact of
deferred CN (Table), whereby induction with standard
ICI-based therapies are performed and if there is absence
of PD, then randomization to CN takes place. In
NORDIC-SUN, having >3 IMDC risk factors at the time
of assessment is deemed not suitable for CN. The study
designs of SWOG-1931 and NORDIC-SUN are likely reflective
of growing acknowledgement that deferred CN
is becoming the preferred approach allowing for a period
of assessment of disease response and biology to systemic
therapy prior to advancing to CN even in the contemporary
immunotherapy era in mRCC.
Conclusion
In patients with mRCC deemed candidates for CN, the
initial treatment approach and optimal sequencing of
CN and systemic therapy has yet to be definitively established.
However, a growing consensus is that nonselective
use of CN to treat clear cell mRCC is unlikely to
provide a meaningful survival benefit. Selection of candidates
for CN should be performed in a multidisciplinary
team-based setting incorporating conventional risk
or prognostic stratification systems. Based on recent seminal
studies of CN in mRCC patients treated with VEGFTKIs,
there is evidence to support that response to
presurgical systemic therapy and upfront systemic therapy
should be prioritized over surgery. This is reflected
in modern phase III study designs whereby the impact
of deferred CN is being evaluated in mRCC patients
treated with current immunotherapy-based combinations.
Results from these ongoing studies are eagerly anticipated
as the role of CN in the immunotherapy era
remains undefined.
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