Therapeutic side effects may also be used as biomarkers. For example, mTOR inhibitors (mTORi), such as everolimus and temsirolimus—which are frequently used in RCC—have a significant side effect profile, including nausea, diarrhea, mucositis, skin rash lymphopenia, elevated cholesterol and triglycerides, anemia, and pulmonary toxicity.9 Pneumonitis is, interestingly, a “biomarker” for better clinical outcomes among patients receiving everolimus and temsirolimus.

To further evaluate the role of toxicities as a potential biomarker for disease response, one group retrospectively reviewed data from 75 patients with metastatic RCC receiving an mTORi. Patients with the highest onset rate of hyperglycemia and hypophosphatemia had the highest progression-free survival. Progression-free survival was lower among those patients with the quicker onset of lymphopenia. Other studies showed that patients who develop hypertension and hypothyroidism while receiving bevacizumab or sunitinib have better overall RCC outcomes.

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As the world of biomarkers in RCC continues to develop, there is no consensus among the urologic and oncology societies on which biomarker(s), if any, should be routinely ordered. The American Urological Association even recommended against the routine use of biomarkers (such as Ki-67, p-53 and VEGF) in a 2013 guideline.10 The European Society of Medical Oncology (ESMO) does not mention biomarkers at all in their 2016 guidelines.11 These guidelines could lead to either under-utilization or a “shotgun” approach, where a multitude of biomarkers are unnecessarily ordered.

As more data regarding biomarkers accumulate, there may be a way to combine several biomarkers into one “panel” that could provide the best outcomes data for patients. One research group derived a biomarker panel that consisted of 5 specific biomarkers (N- and E-cadherin, Ki-67, Cyclin D1, and p-4EB1) that provided prognostic information for a subgroup of patients.12

Despite the efforts and research to date regarding biomarkers in RCC, it would currently be difficult to replace a thorough clinical assessment with any biomarker. But biomarkers will undoubtedly continue to be an important component of determining patient prognosis, identifying the best treatments for each individual patient, and assisting in monitoring how patients respond to treatment.

RELATED: Dalantercept and Axitinib in Renal Cell Carcinoma

New and old biomarkers should be included in clinical trials to help build a database from which oncologists can draw sound clinical recommendations.


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