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Page 10 of 14 Atmaja et al. J Cancer Metastasis Treat 2021;7:xx https://dx.doi.org/10.20517/2394-4722.2021.66

On-treatment predictive markers
The paucity of predictive biomarkers in mRCC renders it difficult for a clinician to foresee treatment
response. In recent years, it has become apparent that on-treatment predictive markers are important in
determining response to therapy.

VEGF-targeted therapies e.g., Sunitinib, have common adverse effects which have been identified as
[75]
potential biomarkers of clinical efficacy. These include hypertension, neutropenia and hypothyroidism .
Treatment-related hypertension occurs in approximately one third of patients on Sunitinib . In a large,
[76]
retrospective study by Rini et al. , patients with a systolic blood pressure of ≥ 140 mmHg had a
[76]
significantly improved ORR to Sunitinib, when compared with patients without systolic hypertension. PFS
and OS were also longer. Further research suggests that the higher the blood pressure, the greater the
systemic VEGF receptor blockade, which in turn, increases the treatment efficacy . However, there is
[77]
insufficient outcome data to justify changes in ongoing treatment based on these clinical biomarkers only.

Oligometastatic renal cell carcinoma
The most common sites of metastatic disease in RCC are the lung (45%), bone (30%), lymph nodes (22%)
and liver (20%) .
[78]
Sites of metastatic disease can be targeted using local therapies; this can include surgical resection
(metastasectomy) and radiotherapy. These local therapies form an important part of an individualized
management plan for patients with mRCC. Evidence suggests that a metastatectomy with curative intent is
associated with a good long-term survival rate, particularly in younger patients with a long disease-free
interval and a solitary site of metastasis .
[79]
Stereotactic radiation therapy and cryotherapy are two non-invasive local therapies that are increasingly
being used for oligometastatic RCC. They are also beneficial when utilized after systemic therapy to
[81]
suppress residual masses . Aoun et al. concluded that cryoablation is a safe and effective procedure in
[80]
the management of RCC. Additionally, a study by Wang et al. reported that 1-year local control rates of
[80]
extracranial metastatic sites were > 90% post stereotactic radiation therapy.
Emerging data from clinical trials suggests that there may be a direct and abscopal response observed when
a combination of immunotherapy and ablative therapy is used to treat mRCC . However, systemic therapy
[82]
is yet to be proven beneficial following complete resection of metastatic disease; the ongoing ECOG 2810
research study has, thus far, found that treatment with Pazopanib for one year after surgery does not
[83]
improve chances of survival .

CONCLUSION
The development of several novel therapies over recent years has revolutionized the treatment of metastatic
RCC. The use of ICIs and TKIs, and their combinations, across multiple lines of therapy, have significantly
improved the overall survival of patients. However, it is now becoming increasingly important for us to
establish a more individualized treatment plan for mRCC, using both clinical and biological prognostic
factors to guide us.

The IMDC, a clinical prognostic tool, is routinely used in practice worldwide; the model stratifies risk into
three groups: favorable, intermediate and poor. Nevertheless, there is a distinct paucity of research that
demonstrates any reliable predictors to therapy response. Advances in tumor genomic profiling have