Page 8 - Management of advanced kidney cancer: KCRNC

hotte et al

In patients with metastatic or advanced RCC with non- – Patients with mRCC who don’t fall within the two above
clear-cell histologies, enrolment in clinical trials should be categories should be offered initial treatment with sys-
encouraged whenever possible. Other options include suni- temic therapy, with consideration of cytoreductive
tinib, sorafenib, temsirolimus, and pazopanib (Table 3). 75-79 nephrectomy given to those with a significant clinical
Two phase 2 trials randomized patients to everolimus response.
vs. sunitinib as first-line therapy for non-clear-cell patholo- The recommendations for cytoreductive nephrectomy
gies with crossover allowed at progression. The ESPN trial come from a recent KCRNC consensus statement by Mason
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futility analysis resulted in early termination of the trial due and colleagues. These recommendations were based large-
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to inferior PFS and OS for everolimus. The ASPEN trial ly on two randomized, controlled studies published in 2018:
demonstrated sunitinib was superior to everolimus for PFS. 81 CARMENA and SURTIME. 87,88 It should be noted that these
Thus, sunitinib is the preferred first-line targeted treatment key pieces of evidence regarding cytoreductive nephrectomy
for non-clear-cell RCC. and systemic therapy are both from the VEGF-targeted era.
In patients with advanced or metastatic sarcomatoid or To what extent these are applicable in the era of immune
poorly differentiated RCC, options show modest responses and checkpoint inhibition has yet to be investigated.
include sunitinib, sorafenib, temsirolimus, and chemotherapy
(Table 3). 75-77,82 In a phase 2 study, the combination of sunitinib 2.4 Role of local therapy in oligometastases
and gemcitabine has been shown to be tolerable and the com-
bination may be more effective than either therapy alone. 83 – In select patients with a limited number of sites of
A recently presented post-hoc analysis of patients with sar- metastatic disease and stable clinical condition, local
comatoid mRCC randomized to immunotherapy or sunitinib therapy, such as resection and/or stereotactic body
in the CheckMate 214 study suggests significant efficacy of radiotherapy, to treat of all sites of metastatic disease
immunotherapy compared to sunitinib. The ORR was 56.7% may be a reasonable option.
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for immunotherapy compared to 19.2% for sunitinib, with CR
proportions of 18.3% vs. 0%. Median OS was 31.2 months 2.4.1 Metastatectomy
compared to 13.6, again favoring immunotherapy (HR 0.55; There are no randomized trials showing the benefit of metas-
95% CI 0.33–0.90; p<0.0155). Rini and colleagues also pre- tasectomy in RCC with oligometastatic disease. However,
sented a post-hoc analysis of similar patients, which showed an among patients with metachronous metastases after nephrec-
ORR rate of 59% compared to 31.5% with pembrolizumab + tomy, about one-third are eligible for metastasectomy and
axitinib compared to sunitinib. CR rate was 12% for the com- several large cohorts report 50% five-year survival follow-
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bination and 0% for sunitinib. PFS and OS were also improved. ing complete resection of metastases. 89,90 Based on avail-
able observational data, patients most likely to benefit from
2.3 Role of cytoreductive nephrectomy metastasectomy are those diagnosed with metastases after
at least a two-year disease-free interval, those with isolated
– Cytoreductive nephrectomy can be considered in metastases, and those with surgically favorable metastatic
appropriately selected patients presenting with de novo locations (e.g., lung, thyroid, and adrenal). A period of
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mRCC, ideally after a multidisciplinary discussion. This observation is reasonable to confirm that the metastatic
is based on expert consensus of this authorship group. disease is not rapidly progressing. In addition, patients on
o Patients with a good performance status (Eastern systemic therapy should be re-evaluated during their course
Cooperative Oncology Group [ECOG] ≤1 or of disease for the option of metastasectomy to render no
Karnofsky Performance Status [KPS] ≥80%), mini- evidence of disease (NED) either due to favorable response
mal symptoms related to metastases, a resectable or oligoprogression (see section 2.5). There is no defined
primary tumor, and a limited burden of metastatic role for adjuvant systemic therapy after metastasectomy if
disease should be offered upfront cytoreductive a patient is rendered NED.2.4.2 Stereotactic body radio-
nephrectomy followed by metastases-directed ther- therapy (SBRT)
apy, a period of surveillance, or systemic therapy. SBRT is another option for oligometastases. Unlike con-
o Patients with significant systemic symptoms from ventional radiotherapy, SBRT involves delivery of very con-
metastatic disease, active central nervous system formal, ultra-hypofractionated radiation over 1–5 fractions,
metastases, a limited burden of disease within the where the goal is to eradicate or provide long-term local
kidney relative to the cumulative extra-renal volume control of the treated tumor(s). In patients with medically
of metastases, rapidly progressing disease, a poor inoperable, early-stage RCC, SBRT to the primary tumou
performance status (ECOG >1 or KPS <80%), and/ results in very high local control rates. 92,93 Similar high local
or limited life expectancy should not undergo cyto- control rates of approximately 90% are observed when using
reductive nephrectomy. SBRT to treat RCC metastases in various body sites (thoracic,

350 CUAJ • October 2019 • Volume 13, Issue 10