







































*Mortality Rate is calculated by:
Mortality Rate=(Estimated Deaths)/(Estimated New Cases)

Figure 1: Mortality rates among common genitourinary 
malignancies. Renal cell carcinoma has the greatest mortality 
rate (nearly 23%) among the common genitourinary cancers, 
followed by bladder cancer (approximately 21%), endometrial 
cancer (approximately 18%), and prostate cancer (nearly 18%). 
Figure is based on “Cancer Facts & Figures 2018” (American 
Cancer Society, 2018).

Abstract: Renal cell carcinoma is a malignancy of the kidney, and is among the most common and lethal cancers 
a!ecting the genitourinary tract in males and females. As the kidneys play a critical role in maintaining homeostasis 
in an organism (particularly by regulating excretion and reabsorption of solutes, in"uencing hormone release, and 
maintaining blood pressure), malignancies of these organs have several complex side e!ects. #e most common 
genetic de$ciency observed in renal cell carcinoma is inactivation or mutation of the von Hippel-Lindau (VHL) 
tumor suppressor gene, which is critical for hypoxia-induced angiogenesis and has generated several hypotheses on 
how to treat the malignancy.%A&er the initial surgery or radiation to the localized disease, systemic pharmacological 
agents are utilized to prolong survival once the cancer has metastasized. #e aim of this review is to present the 
evolution of pharmacological agents in managing renal cell carcinoma. In its three main sections, this review will 
explore cytokine immunotherapies utilized in the 1990s, vascular endothelial growth factor-tyrosine kinase inhibitor 
(VEGF-TKIs) systemic therapies devised in the 2000s, and $nally treatment with targeted immunotherapies. With 
the rapid pace of pharmaceutical development, the prognosis for renal cell carcinoma continues to improve.

Aisthesis      Volume 11,  20201

!e Past, Present, and Future of Renal Cell Carcinoma 
Treatment: A Systematic Review

by Nityam Rathi

Introduction
 Renal cell carcinoma is a malignancy of the kidney 
and is among the most common cancers a!ecting 
the genitourinary tract in males and females. While 
much progress has been made in the management 
and diagnosis of renal cell carcinoma, it remains one 
of the most lethal cancers, giving rise to more than 
140,000 cancer-related deaths yearly (Capitanio et 
al., 2019). Among the most common genitourinary 
malignancies (including renal cell, bladder, prostate, 
and endometrial cancers), renal cell carcinoma has 
the greatest mortality rate (Figure 1) (American 
Cancer Society, 2018). Because the kidneys play 
a critical role in maintaining homeostasis in an 
organism—particularly by regulating excretion and 
reabsorption of solutes, in"uencing hormone release, 
and maintaining blood pressure—malignancies of 
these organs have several complex side e!ects. #e 
hallmarks of kidney cancer include blood in the 
urine, chronic pain in the back, fever, fatigue, and 
ultimately death from metastasis. Common sites of 
metastasis include the lungs, bones, lymph nodes, 
liver, adrenal glands, and brain (Bianchi et al., 2012); 
as such, treating this cancer early on may prevent 
failure of other necessary organ systems. Over the 
last 30 years, the treatment landscape for renal cell 

carcinoma has changed drastically, as more has been 
learned about its development and progression. 
 Renal cell carcinoma can be inherited or sporadic. 
Patients who inherit mutations that give rise to 
renal cell carcinoma typically begin demonstrating 



!e Past, Present, and Future of Renal Cell Carcinoma Treatment

Aisthesis      Volume 11,  20202

numerous cancerous nodules in the kidney at around 
age 37, while the more common sporadic renal cell 
carcinoma presents as a solitary tumor at around 
age 61 (Pavlovich et al., 2003). Regardless of the 
age of onset or etiology pattern, the most common 
genetic de$ciency observed in renal cell carcinoma 
is inactivation or mutation of the von Hippel-Lindau 
(VHL) tumor suppressor gene (Latif et al., 1993). 
#e protein encoded by the VHL gene has numerous 
functions, but its role in angiogenesis (the creation 
of new blood vessels) in response to hypoxia has 
generated several hypotheses on how to treat the 
malignancy. #e question that I seek to answer is: 
how have the elucidation of the angiogenesis pathway 
and other discoveries on its pathology changed the 
treatment of renal cell carcinoma? 
 Whereas radiation and/or nephrectomy were 
the only defenses in the past, modern management 
of the cancer is more comprehensive. A&er the initial 
surgery or radiation—depending on whether the 
disease presents as metastasized or not—systemic 
pharmacological agents are utilized to prolong 
survival for both familial and sporadic cases of renal 
cell carcinoma. #e aim of this review is to present 
the evolution of pharmacological agents in managing 
renal cell carcinoma. In its three main sections, 
this review will explore cytokine immunotherapies 
utilized in the 1990s, vascular endothelial growth 
factor-tyrosine kinase inhibitor (VEGF-TKIs) 
systemic therapies devised in the 2000s, and $nally 
treatment with targeted immunotherapies. With 
the rapid pace of pharmaceutical development, 
the prognosis for renal cell carcinoma continues to 
improve.

1990s: !e Age of Cytokine Immunotherapies
 Between 1900 and 1987, sporadic cases of 
spontaneous regression of renal cell carcinoma 
were detected in patients who were simultaneously 
experiencing bacterial infections (Challis & Stam, 
1989). Clinicians hypothesized that such cases, 
although rare, may have arisen due to the activation 
of the patients’ immune system in response to the 
bacterial infection. Such hypotheses led to the 
labeling of renal cell carcinoma as “immunogenic.” 
Once engaged to combat the bacterial infection, the 
immune system likely discovered the cancerous cells 
in the body and generated an immune response that 

ultimately induced cancer regression. Scientists and 
clinicians subsequently tested this hypothesis by 
developing cytokine immunotherapies. In general, 
cytokine immunotherapies generate a widespread 
activation of immune cells in the body, such as B 
cells, T cells, and macrophages, that ultimately target 
the cancer.
 By the early 1990s, cytokine immunotherapies 
were primarily used in the post-surgery and/or 
metastatic renal cell carcinoma setting with the 
goal of reducing the intensity of the cancer. Two 
of the most signi$cant drugs developed were 
synthetic High Dose-Interleukin 2 (HD-IL2), and 
Interferon alfa-2', o&en denoted as IFN-' in the 
clinic. Mechanistically, these two therapies di!er. 
HD-IL2 induces the proliferation of immune cells 
and stimulates these cells to target the cancer, while 
IFN-' makes tumor cells more immunogenic. In 
murine models, a combination of HD-IL2 and IFN-' 
was found to be correlated with anti-tumor activity 
(Brunda et al., 1987). 
 To assess whether the same would hold in 
metastatic renal cell carcinoma patients, a phase II 
clinical trial was devised to compare survival and 
toxicities in patients treated with HD-IL2 alone or 
with the HD-IL2/IFN-' combination (Atkins et al., 
1993). Atkins et al. (1993) hypothesized that, given 
unequivocal evidence of anti-tumor activity of 
the HD-IL2/IFN-' combination in in vivo studies, 
similar trends would be seen in humans. In the 
phase II trial, Atkins et al. included 99 patients 
with metastatic renal cell carcinoma. 28 patients 
were administered the combination HD-IL2/IFN-' 
treatment, and 71 patients were administered HD-
IL2 treatment alone. Researchers then followed up 
with all patients for 26 months to track survival, 
encountered toxicities, and response. 
 It was found that, although median survival 
rates were nearly equal for the HD-IL2 and HD-IL2/
IFN-' arms (Figure 2; 15.5 months vs. 16 months, 
respectively), response rates were higher for the HD-
IL2 arm (17% vs. 11%, respectively). Furthermore, 
di!erences in toxicity were observed. Signi$cantly 
more neutropenia (low white blood cell count) and 
myocarditis/ischemia (reduced blood supply to 
the heart) were noted on the HD-IL2/IFN-' arm, 
while serum bilirubin was signi$cantly elevated (an 
indicator of liver damage) in patients on the HD-IL2 
arm. Nevertheless, improved response rates with 



Figure 2: Response to di"erent cytokine immunotherapy 
treatment regimens in renal cell carcinoma. Patients were giv-
en either (a) a combination of HD-IL2 and IFN-' (n=28), or 
(b) HD-IL2 exclusively (n=71) via bolus intravenous injection 
every 8 hours, days 1 to 5 and 15 to 19. HD-IL2 was given at a 
dosage of 0.8 mg/m2 and IFN-' at a dosage of 3 x 10(6) U/m2 in 
the combination arm, and HD-IL2 was given at a dosage of 1.33 
mg/m2 when given as a monotherapy. 
A) Survival conferred with the HD-IL2/IFN-' combination 
treatment. Mortality rate at 24 months is approximately 70%. B) 
Survival conferred with the HD-IL2 single treatment. Mortality 
rate at 24 months is approximately 70%. (Figure adapted from 
Atkins et al., 1993.) 

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Aisthesis      Volume 11,  20203

HD-IL2 therapy, in comparison with other cytokine 
immunotherapies, were observed in additional 
phase II trials (Fyfe et al., 1995).
 In the broader context of renal cell carcinoma 
treatment, this phase II trial led by Atkins et al. 
showed that cytokine immunotherapies confer a 
survival bene$t to metastatic renal cell carcinoma 
patients. Unlike the $ndings in murine models, 
therapy with HD-IL2 alone was found to produce 

meaningful and durable responses with manageable 
and reversible toxicity in renal cell carcinoma 
patients. A possible reason for the di!erences in 
outcomes of the two arms is that the HD-IL2/IFN-' 
arm may have over-activated the immune system. 
An excessive number of activated immune cells 
(such as B cells, T cells, and macrophages) may lead 
to scenarios of autoimmunity, in which the immune 
system erroneously identi$es normal cells in organs 
as dangerous, and subsequently attacks them. 
Although cytokine immunotherapy was approved 
by the FDA for treatment of renal cell carcinoma in 
1992, the need for more speci$c, targeted therapies 
to reduce toxicities and further improve survival was 
established.

2003-Present: Sunitinib and Other Targeted, 
Pathway-Speci#c VEGF-TKI !erapies
 While the pathogenesis of kidney cancer is quite 
complex, mutations in the VHL gene are known to 
play a role in cellular physiology by upregulating 
the expression of the vascular endothelial growth 
factor (VEGF) gene. #e protein encoded by VEGF 
plays a critical role in forming blood vessels that 
carry nutrient-rich blood to the site of the tumor. 
Ultimately, this leads to tumor growth and provides 
an escape path for malignant cells, which increases 
the probability of metastasis. #e angiogenesis 
pathway is initiated by the binding of VEGF to the 
VEGF Receptor (VEGFR), which conducts the 
signal via tyrosine-kinase activity. In all, there are 
three VEGFR to which the VEGF ligand can bind: 
VEGFR-1, VEGFR-2, and VEGFR-3. Ligand-receptor 
binding can result in one or more of three critical 
outcomes that yield angiogenesis: endothelial cell 
migration (the lining up of endothelial cells to form 
a blood vessel), a change in vascular permeability 
(the capacity of blood vessel to allow entry of 
nutrients to enrich the blood), and endothelial cell 
proliferation (the replication of endothelial cells that 
will ultimately line the blood vessel) (Morabito et al. 
2006). Upon discovery of VHL mutations and their 
consequences for the angiogenesis pathway, the novel 
idea of targeting such a speci$c cellular pathway with 
synthetic chemicals in hopes of mitigating cancer 
growth became popular. 
 Blocking angiogenesis with inhibitory 
pharmacological agents (known as VEGF-Tyrosine 
Kinase Inhibitors, VEGF-TKIs) revolutionized the 



Figure 3: Targets of di"erent VEGF-TKI therapies. 
Although VEGF-TKIs achieve the same result of preventing an-
giogenesis, each drug has a di!erent speci$city. Of the diverse 
TKIs shown above, Sunitinib, Axitinib, and Sorafenib are more 
widely utilized in treatment of renal cell carcinoma. Sunitinib 
and Axitinib each preferentially target both VEGFR-1 and 
VEGFR-2, and Sorafenib targets VEGFR-2 and MEK. Figure 
modi$ed from Morabito et al., 2006.

Figure 4: Progression-Free Survival (PFS) is Greater in Pa-
tients Treated with Sunitinib than IFN-$. A total of 750 pa-
tients were randomized in a 1:1 ratio to either the Sunitinib 
treatment arm or the IFN-' arm. Sunitinib was administered 
orally at a dose of 50 mg once daily, taken without regard to 
meals, in 6-week cycles consisting of 4 weeks of treatment fol-
lowed by 2 weeks without treatment. IFN-' was administered 
subcutaneously three times per week on nonconsecutive days at 
3 MU per dose during the $rst week, 6 MU per dose the sec-
ond week, and 9 MU per dose therea&er. PFS conferred with 
the Sunitinib treatment was approximately 11 months, while 
PFS conferred with the IFN-' treatment was approximately 5 
months (Motzer et al., 2007).

!e Past, Present, and Future of Renal Cell Carcinoma Treatment

Aisthesis      Volume 11,  20204

treatment of renal cell carcinoma. Drugs of this 
class include Sunitinib, Cabozantinib, Sorafenib, 
and Axitinib, among others (Figure 3), and 
each drug inhibits unique component(s) of the 
angiogenesis pathway. In mouse xenogra& models, 
Sunitinib was found to reduce tumor microvessel 
density, con$rming the drug’s potential to reduce 
angiogenesis and inhibit tumor growth (Mendel et 
al., 2003). 
 To assess whether Sunitinib could further 
improve survival bene$ts o!ered by cytokine 
immunotherapies in renal cell carcinoma, a phase 
III multicenter clinical trial was formulated. #is 
trial compared progression-free survival (PFS)—the 
time between treatment initiation and observation 
of cancer progression—in patients treated with 
Sunitinib or IFN-' (Motzer et al., 2007). Given 
pre-clinical evidence of Sunitinib’s anti-angiogenic 
properties and preliminary clinical data, Motzer et 
al. hypothesized that Sunitinib would yield superior 
outcomes when compared with IFN-'.  In the phase 
III trial, Motzer et al. included 750 patients with 
metastatic renal cell carcinoma randomized in a 
1:1 ratio to the Sunitinib or IFN-' treatment arms. 
Patients in both groups continued treatment until 
the occurrence of disease progression. 
 It was found that PFS was signi$cantly higher 
for the group treated with Sunitinib as compared to 
IFN-' (11 months vs. 5 months, respectively; Figure 

4). Furthermore, a greater percentage of patients 
treated with IFN-' had to discontinue treatment due 
to secondary medical consequences of the drug as 
compared to those treated with Sunitinib (13% vs. 
8%, respectively). However, the incidence of certain 
toxicities was greater in the Sunitinib arm than the 
IFN-' arm. 6.4% of patients on the Sunitinib arm 
experienced hypertension, as compared to 0.3% 
on the IFN-' arm, and 14.1% of patients on the 
Sunitinib arm experienced diarrhea, as compared to 
3.3% on the IFN-' arm. Similar $ndings of enhanced 
survival, coupled with cardiovascular toxicities 
during treatment with VEGF-TKIs have been noted 
in subsequent clinical studies (Schmidinger et al., 
2008; Catino et al., 2018).
 #e development of VEGF-TKIs was a major 
landmark in renal cell carcinoma treatment. #e 
phase III trial led by Motzer et al. showed that 
targeted inhibition of the angiogenesis pathway with 
Sunitinib could improve PFS and quality-of-life in 
patients with metastatic renal cell carcinoma. Yet, 
the upsurge of cardiovascular toxicities became of 
concern when prescribing Sunitinib. It is known that 
the same VEGF pathway is used by healthy cells, 
such as those in the cardiovascular system, to receive 



Figure 5: Nivolumab and Ipilimumab mechanism of action. 
A) Nivolumab is an antibody that binds to the PD-1. While 
PD-1 normally binds Programmed Death-Ligand 1 (PD-L1) 
expressed on tumor cells, ultimately resulting in death of the T 
cell, Nivolumab binds with greater a(nity, thereby preventing 
death of the T cell (Guo et al., 2017). B) Full activation of the T 
cell involves binding of the antigen from the Antigen-present-
ing cell (le&) and binding of co-receptor CD28 with a receptor 
(B7) on the Antigen-presenting cell. Normally, the second re-
ceptor on the Antigen-Presenting cell (B7) binds to CTLA-4, 
thereby hindering T cell activation. C) Ipilimumab (denoted as 
' CTLA-4) binds to the CTLA-4 receptor on the T cell, induc-
ing full activation of the T cell. B and C are adapted from Lipson 
& Drake, 2011.

!e Past, Present, and Future of Renal Cell Carcinoma Treatment

Aisthesis      Volume 11,  20205

nutrients from blood. Renal cell carcinoma patients 
who present with poor cardiovascular health are 
o&en administered Sunitinib in combination with 
drugs that moderate hypertension. If cardiovascular 
health is to the point that the safety of the patient 
would be compromised with VEGF-TKIs, Sunitinib 
is forgone completely.  Nevertheless, the e(cacy of 
Sunitinib in improving survival outcomes led to its 
establishment as a $rst-line of therapy for renal cell 
carcinoma in the post-surgery or radiation setting. 
#e revolutionary paradigm of targeted, pathway-
speci$c cancer therapies has since been explored in 
the immunological context.

2009-Present & Future: Targeted Immunotherapies: 
Stimulating the Immune System at a More Re#ned 
Level
 In an attempt to o!er further lines of treatment 
for metastatic renal cell carcinoma patients, 
investigators revisited the idea of renal cell 
carcinoma as “immunogenic” with the paradigm 
of targeted therapies. In 2004, it was $rst reported 
that T cells, particularly cytotoxic T cells, could 
be isolated in higher levels from patients with 
regressing metastatic kidney cancer (Takahashi et 
al., 2004). Subsequent studies revealed that increased 
expression of PD-L1 (Programmed-Death Ligand 
1) molecules on the cell surface of cancer cells over 
time is associated with a poor prognosis in renal 
cell carcinoma patients because PD-L1 binds to the 
PD-1 (Programmed Death Protein-1) receptors on 
the T cell, thereby inhibiting the T cell-mediated 
immune response (#ompson et al., 2006). By 
inducing death of the T cells, cancer cells could 
evade the host immune system. Together, these two 
discoveries created the basis for the clinical use of 
targeted immunotherapies that would block the PD-
L1/PD-1 interaction, thereby stimulating the T cell-
mediated immune response against cancerous cells 
in a more speci$c manner as compared to previous 
cytokine immunotherapies.
 Since 2009, two novel targeted immunotherapies 
have entered clinical trials. #e $rst is Nivolumab, 
an immune checkpoint inhibitor antibody that 
blocks the Programmed Death-1 (PD-1) receptor 
found on T cells, thereby preventing the PD-1/PD-
L1 interaction that results in death of the T cell. 
#e second is Ipilimumab, a T-cell potentiator that 
works by blocking cytotoxic T-lymphocyte antigen-4 

(CTLA-4), a receptor on the T cell that inhibits 
stimulatory signaling upon binding to its ligand. 
E!ectively, both therapies remove inhibitory signals 
and promote antitumor activity (Figure 5). A small 
phase I clinical trial showed that metastatic renal 
cell carcinoma patients treated with Nivolumab 
experienced manageable toxicities and durable 
responses that, in some cases, persisted a&er drug 
discontinuation (McDermott et al., 2015). Although 
not used as a monotherapy for renal cell carcinoma, 
Ipilimumab led to improved survival outcomes 
as compared to those treated with standard-of-
care glycoprotein peptide vaccine treatment (10.0 
months vs. 6.4 months) in metastatic melanoma 
patients (Hodi et al., 2010). Success of both of these 
treatments as monotherapies led to the hypothesis 
that these two drugs may have a synergistic e!ect 
when used in combination (Melero et al., 2015).
 In the CheckMate 0214 trial, a phase III clinical 
trial, approximately 850 intermediate or poor-risk 
renal cell carcinoma patients were enrolled and 



Figure 6: Overall Survival and Progression-Free Survival 
is greater for patients treated with Nivolumab + Ipilimum-
ab than with Sunitinib. A) Overall Survival is determined by 
calculating percentage of patients who have survived at a given 
time point (i.e: 12 months, as demarcated above) a&er initiating 
a treatment. Advanced renal cell carcinoma patients who re-
ceived Nivolumab and Ipilimumab demonstrated much higher 
survival rates than those who were treated with Sunitinib at any 
given time point. B) Progression-free Survival is determined by 
calculating percentage of patients who are not only surviving on 
a treatment, but also do not demonstrate any signs of worsening 
disease at a given time point. Advanced renal cell carcinoma pa-
tients who received Nivolumab and Ipilimumab demonstrated 
longer progression-free survival than those who were treated 
with Sunitinib (Motzer et al., 2018).

!e Past, Present, and Future of Renal Cell Carcinoma Treatment

Aisthesis      Volume 11,  20206

randomized to one of two treatment arms: Nivolumab 
and Ipilimumab (425 patients), or Sunitinib (422 
patients) (Motzer et al., 2018). Researchers followed 
up with these patients to track overall survival and 
progression-free survival to compare the e(cacies of 
the di!erent treatment arms.
 It was observed that patients on the Nivolumab 
+ Ipilimumab arm had superior survival outcomes 
than patients on the Sunitinib arm (Figure 6). 
Patients treated with the Nivolumab + Ipilimumab 
combination had a greater duration of overall 
survival (Not Reached vs. 26.0 months, respectively) 
and progression-free survival (11.6 months vs. 
8.4 months) than those treated with Sunitinib. 

Cardiovascular toxicities and other severe adverse 
events were signi$cantly lower for the Nivolumab 
+ Ipilimumab arm as compared to the Sunitinib 
arm. #ese $ndings provide support for the use of 
Nivolumab and Ipilimumab as a $rst-line of therapy 
for metastatic renal cell carcinoma. 
 #e phase III trial led by Motzer et al. has 
helped establish combination immunotherapy as 
a new approach to treating renal cell carcinoma. 
Stimulating the immune system more speci$cally 
than previous cytokine immunotherapies has 
reduced many of the side e!ects previously observed 
with cytokine immunotherapies, which induce 
extensive activation of the immune system. Current 
e!orts are geared toward evaluating the implications 
of treatment regimens, which include a combination 
of targeted immunotherapies and VEGF-TKIs to 
assess whether cross-talk between the drug actions 
may modulate toxicities previously observed with 
VEGF-TKIs (National Cancer Institute, 2018). 
Additionally, in an attempt to develop personalized 
treatment regimens, researchers are exploring gene 
expression levels, primarily of proteins found in the 
tumor microenvironment that may be predictive of 
adverse or positive responses to immune checkpoint 
inhibitors (Zhu et al., 2019).

Conclusion
 Over the last thirty years, our ability to treat 
patients with advanced renal cell carcinoma has 
greatly improved. Whereas nephrectomy and/
or radiation were once the only options available 
and were only su(cient to eradicate the cancer if 
detected early enough, it soon became clear that the 
use of pharmacological agents would be needed to 
manage more aggressive renal cell carcinoma. 
 #e 1990s saw an upsurge in the use of cytokine 
immunotherapies, such as HD-IL2 and IFN-', 
which activated various cells of the human immune 
system. Despite improving survival of metastatic 
renal cell carcinoma patients, treatment with HD-
IL2 and/or IFN-' o&en led to severe side e!ects 
as a result of an overactive immune system. Upon 
elucidation of key molecular pathways involved in 
the onset and progression of renal cell carcinoma, 
the early 2000s were characterized by the use of 
pathway-speci$c VEGF-TKIs such as Sunitinib. 
#ese drugs prevented cancer cells from receiving 
nutrients from the blood supply, but also adversely 
a!ected healthy cells, given that both use the 



!e Past, Present, and Future of Renal Cell Carcinoma Treatment

Aisthesis      Volume 11,  2020

same angiogenesis pathway. Nevertheless, the 
survival rates were unequivocally superior to those 
observed in cytokine immunotherapies, which led 
to the FDA-approval of VEGF-TKIs as a $rst line of 
treatment in the post-surgical and radiation setting. 
Recent pharmacological research has applied the 
concept of pathway-speci$c cancer therapies in 
developing targeted immunotherapies (Nivolumab 
and Ipilimumab) since the late 2000s. Targeted 
immunotherapies are devoted to activating the 
patient’s immune system in a more speci$c manner 
(as compared to cytokine immunotherapies) by 
blocking the PD-1/PD-L1 interaction that inhibits 
the immune response against cancer. #e ongoing 
CheckMate 0214 trial has shown that combining 
Nivolumab and Ipilimumab yields even better 
survival outcomes than VEGF-TKIs, indicating that 
immunotherapy agents may be superior in managing 
renal cell carcinoma.
 With the accumulation of several treatment 
options for renal cell carcinoma, we have entered into 
an exciting era of developing personalized treatment 
regimens for di!erent cohorts of patients. Can we 
predict who will respond well to immunotherapies? 
Does combining immunotherapies with other types 
of anti-cancer drugs confer even better survival 
outcomes? As the $ndings from new clinical trials 
are published, the treatment and management of 
renal cell carcinoma will continue to evolve.

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!e Past, Present, and Future of Renal Cell Carcinoma Treatment

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