Factors Influencing Survival

On multivariate analysis, treatment in the targeted era was associated with a 13% decreased risk of death compared with treatment in the cytokine era.

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Clear-cell histology was associated with a 24% decreased risk of death compared with other histologic subtypes. Patients who underwent cytoreductive nephrectomy had a 57% decreased risk of death compared with those who did not.

The researchers acknowledged some study limitations. For example, they did not have available granular information, which portends mRCC prognosis. “Therefore, we cannot account for performance status, key laboratory values, or sites and burden of metastatic disease volume.”

In addition, as a result of increased use of imaging during the targeted therapy era, patients treated in this era may have been diagnosed earlier in the course of their disease than those treated in the cytokine era.

The researchers said the difference in overall survival between their study and trial data may relate to the more stringent selection criteria for inclusion in clinical trials compared with population-based SEER data. “SEER captures a heterogeneous health care delivery system and patients with disparate access to new agents and decision making,” they wrote.

“Many cases may be treated without histologic information, predisposing patients to care with less beneficial agents.”

Eric A. Singer, MD, MA, assistant professor of surgery and director of the Kidney Cancer Program at the Rutgers Cancer Institute of New Jersey in New Brunswick, who was not involved in the new study, commented that the investigation by Dr. Macleod’s group is important but has some weaknesses, such as the exclusion of the 2 most recently approved drugs for treating mRCC (pazopanib in 2009 and axitinib in 2012). “It illustrates that this study is limited by the time period it is examining,” Dr. Singer said, adding that pazopanib often is used as first-line therapy.

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“However, I suspect even with the inclusion of pazopanib and axitinib in the study, if we could examine data through 2015, we would still see shorter survival compared to the published clinical trials.” This most likely would be due to differences between the study populations and the general population.