In the past decade, cancer research has delved into the biologic factors driving cancer growth — but while there have been impressive successes in finding novel and effective therapies, there has not been as much success in finding the biomarkers in renal cell carcinoma (RCC) that can successfully predict for response or clinical outcomes with specific agents. But that time is coming, according to experts.

“Individualized care using predictive biomarkers is central to the treatment of other advanced malignancies,” according to Jeffrey Graham, MD, and coauthors of a recent article entitled “Personalized Management of Advanced Kidney Cancer,” which was published in the 2018 American Society of Clinical Oncology Educational Book.1 “The elucidation of predictive factors is an unmet need in metastatic RCC and an area of active research.”

The “biggest asset in targeted therapy” has been the improved efficacy, said Ulka Vaishampayan, MD, of the Karmanos Cancer Center in Detroit, Michigan, who was corresponding author of the article. “With newer agents, there is a broader application and better efficacy, a higher response rate, and, overall, we’re now hitting more targets within the tumor.”

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Prognostic Models

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is “routinely used for prognostication in clinical practice,” the authors wrote; it identifies six variables as having prognostic significance.1 Since its initial validation, the model has also shown prognostic stratification in both second- and third-line settings, the authors noted.

Factors associated with a poor prognosis are key to tackling challenging cases, but equally important is identifying factors that do not influence outcomes, Dr Vaishampayan said. In metastatic RCC, age is one of those factors that should not automatically be used as an absolute contraindication to targeted therapy — overall comorbidity risk score should be considered, she said.

Deferred Systemic Therapy

RCC is a highly heterogeneous disease (with clear cell RCC comprising more than 75% of cases) and one that has a varying natural history. Biopsies in RCC tumors “may reveal only a minority of the genetic alterations within the entire tumor” and genomic differences can be noted within a single tumor as well as between primary and metastatic sites.1 For some patients with metastatic RCC, there seems to be a less aggressive and more indolent pattern of progression. Those patients may benefit from deferred systemic therapy with active surveillance, the authors noted.

Localized therapy to sites of metastatic disease will continue to be an important component in the personalized management of RCC; these can include surgical resection, definitive radiotherapy, and other ablative procedures. However, the role of systemic therapy after complete resection of metastatic disease remains unclear.

The role of nephrectomy in the presence of metastatic disease is also changing with contemporary effective therapy. For instance, at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, the CARMENA study (a phase 3 randomized study of patients with metastatic RCC) showed median overall survival for people who received only the targeted therapy sunitinib was 18.4 months, which was noninferior when compared with 13.9 months for those who received surgery followed by sunitinib, the current standard of care.2

“What this found is that for patients with metastatic disease that is progressing or [for those] who are symptomatic, we should not wait and perform surgery, but we should consider initiating systemic therapy first,” Dr Vaishampayan said. “We’ve been doing that for most of our patients who we thought were symptomatic from their cancer and would benefit from immediate systemic therapy, but that may not have been happening routinely. But CARMENA demonstrates that clinicians should consider systemic therapy first in patients with bulky metastatic disease so the nephrectomy time and procedure does not compromise patient care.”