EURURO Vol. 72 No. 6

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resistance to therapy are a priority. There are no
clinically validated biomarkers, but a number of
candidates have been identified, including loss-of-
function mutations in VHL and TSC1; differences in
host genetics such as single nucleotide polymorphisms
in VEGF, HIV-1a, and IL-8; mutations in the tumor
suppressor genes BAP-1 and SETD-2; and a composite
score of circulating biomarkers such as IL-18 [18_TD$DIFF] [19_TD$DIFF]
4 Development and evaluation of new immunothera-
pies for the treatment of kidney cancer, including
immune biomarkers of patient and tumor character-
istics and response.
Immune-oncology (IO) is an exciting new field that
includes checkpoint inhibitors and immune modulators,
cancer vaccines, adoptive cell therapy, monoclonal
antibodies, and cytokines [20_TD$DIFF] Novel IO combina-
tions and sequences with tyrosine kinase inhibitors (IO-
TKI) have the potential to improve outcomes. Results
from ongoing and future trials will help to inform future
strategies. The newly approved but expensive check-
point inhibitor nivolumab, with improved overall
survival [21_TD$DIFF] , is being studied in combination with
cabozantinib, a new small-molecule TKI
(NCT02496208), and ipilimumab, a CTLA4 inhibitor
(NCT02231749). One-third of patients derive no benefit
from PD-1–directed therapy, so we need a biomarker to
avoid ineffective treatment. PD-L1 immunohistochem-
istry may not be reliable [22_TD$DIFF] [23_TD$DIFF] [24_TD$DIFF] .
5 Identification and validation of novel indicators or
biomarkers that can be used to predict the develop-
ment and progression of metastatic kidney cancer.
See above.
6 Assessment of supportive care needs and appropriate
supportive care interventions for patients with
kidney cancer and their families.
This and the next priority might not have been
identified by expert clinicians alone, despite studies
documenting unmet informational and supportive care
needs and suggesting that the treatment of kidney
cancer can impact negatively on physical and psycho-
social functioning [25_TD$DIFF] [26_TD$DIFF] Supportive care inter-
ventions have the potential to improve patient
outcomes [27_TD$DIFF] .
7 Development of decision-making tools for patients
and health care providers to help in guiding
treatment decisions in all stages of kidney cancer.
Decision aids compared to usual care improve
engagement in decision-making, knowledge of options,
and accurate risk perceptions, and reduce decisional
conflict related to feeling uninformed and unclear about
personal values [28_TD$DIFF] . No decision aids have been
developed or evaluated in kidney cancer [29_TD$DIFF]
[30_TD$DIFF] . Patients face a range of complex decisions regarding
surgical alternatives for early-stage cancer or second- or
third-line treatments for metastatic disease. Informa-
tion is frequently presented in inaccessible, academic
formats. Often there is no ‘‘best’’ treatment choice, but
rather a personal decision that incorporates individual
values and preferences. Aids could be developed for
decisions on cytoreductive nephrectomy for newly
diagnosed metastatic disease and on management for
small renal masses (SRMs) [2_TD$DIFF]
8 Defining the role and criteria for using biopsy in the
management of kidney cancer.
Owing to concerns regarding overtreatment of SRMs,
renal tumor biopsy (RTB) has been proposed for
identification of benign SRMs to decrease unnecessary
surgical procedures and possibly delay intervention for
cancers considered to have low metastatic potential
[3_TD$DIFF] [4_TD$DIFF] . There is renewed interest in RTB for assessing
pretreatment tumor histology in metastatic RCC in
order to individualize and personalize therapy [5_TD$DIFF] . The
role of RTB will almost certainly expand to facilitate
personalization of care [6_TD$DIFF] .
9 Evaluation of the impact of differences in regional
funding and access to treatment on patient outcomes
in kidney cancer.
Timely access to quality care and new agents is a
common concern in many countries. There is also
documented variation in practice patterns, whereby
rural residents are less likely to undergo partial
nephrectomy compared to their urban counterparts
[7_TD$DIFF] . Odisho et al [8_TD$DIFF] also found that direct access to a
urologist resulted in a 8–14% reduction in kidney cancer
mortality when compared to patients who have to travel
[8_TD$DIFF] . Future research is needed so that improvement
strategies can be implemented [9_TD$DIFF]
10 Identification of risk factors and cause(s) of kidney
cancer.
Like other cancers, the etiology and risk (and
protective) factors of kidney cancer are not completely
understood. The increase in the incidence of RCC and
other kidney tumors may be in part due to rises in
hypertension and obesity [10_TD$DIFF] Lifestyle and health
behaviors such as physical activity, smoking, and alcohol
consumption may also play a role [11_TD$DIFF] There is also
interest in the role of genetics in the pathogenesis of RCC
[12_TD$DIFF] . While rare, personalized approaches to the care of
mutation carriers can be implemented [13_TD$DIFF] other more
common genetic variants and their interaction with
environmental exposures may influence RCC risk in
nonheritable forms. To date, the majority of studies have
been based on genome-wide association studies, but
results have been mixed [14_TD$DIFF] Advances in next-
generation sequencing will allow more comprehensive
evaluations of common genetic variations [11_TD$DIFF] .
While these top ten uncertainties and resulting research
priorities should not be the sole drivers of the research
agenda, we believe that they should receive careful
consideration by funders and researchers alike. Each of the
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