• Pa ent and tumor reviewed by mul disciplinary team
• Staging confirmed including pathology and imaging
• Evalua on for metastectomy
Stage IV RCC Immunotherapy Treatment Algorithm
Surgical
candidate?
Diagnos
c
Workup
Pa
ent
Selec
on
Ini
al
Therapy
Treatment
Recommenda
ons
Refractory
Pa
ents
YES
Proceed with
metastectomy
Clear cell pathology Non-clear cell pathology
NO
Risk:
1
Good/Intermediate
Risk:
Poor/Sarcomatoid
features
Observa on:
2
1st: Clinical Trial
3
2nd: HD IL-2 or
An -VEGF TKI
4
1st: Clinical Trial
2nd: An -VEGF TKI
1st: Clinical Trial
2nd: An -VEGF TKI
5
Nivolumab
6
TKI, mTOR inhibitor, HD IL-2
1
"Risk" refers to prognos c risk group per Memorial Sloan Ke ering Cancer Center (MSKCC) and/or
Interna onal Metasta c Renal Cell Carcinoma Database Consor um (IMDC) classifica on.
2
For pa ents with small-volume, indolent metastases, an ini al period of observa on that accounts for
pa ent age/comorbidi es, pa ent preference, and toxicity of available therapy can be considered.
3
A clinical trial, including those that are immunotherapy-based, should be considered in all RCC
pa ents in all lines of therapy.
4
As noted in the manuscript, HD IL-2 should be considered and discussed with mRCC pa ents with
clear cell histology and good PS.
5
For pa ents with advanced non-clear cell RCC, a clinical trial is the preferred ini al treatment op on
if available, including trials of checkpoint inhibitors for which limited data exist regarding efficacy
in non-clear cell RCC. If unavailable, then a VEGFR TKI is preferred given results from two small
randomized trials showing a slight advantage over mTOR inhibitors in this se ng.
6
Given overall survival benefit and tolerability, nivolumab is an appropriate ini al recommenda on in
refractory RCC, in the absence of contraindica ons given the overall survival benefit and tolerability.
Other op ons (TKI, HD IL-2 and mTOR inhibitors) can be considered depending on pa ent PS,
comorbidi es, prior therapy received and preference. Figure adapted from Kaufman et al., Nat Rev
Clin Oncol. 2013;10(10):588–98.
