Surgery with targeted therapy benefits metastatic renal cancer patients

Surgery with targeted therapy benefits metastatic renal cancer patients

21 Sep 2016

Survival in metastatic renal cell carcinoma (mRCC) can be doubled, or even more, in patients who had surgery combined with targeted therapy. This was the main outcome of a large retrospective study.

Patients who had a kind of surgery called "cytoreductive nephrectomy" had a median overall survival (OS) of 17.1 months compared with 7.7 months for patients who did not have surgery. Surgery added to survival across the range of patients who lived 6 months or less to those who lived as long as 2 years.

Patients who underwent surgery were younger, more likely to be treated at academic centers, and had less advanced disease, reported Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, and colleagues in the Journal of Clinical Oncology.


Surgery offers longer survival

"The survival advantage of patients who underwent surgical resection was not only maintained compared with non-cytoreductive nephrectomy patients but significantly augmented with increasing lengths of survival even after adjusting for all other covariates," the authors noted.

When feasible, cytoreductive nephrectomy may improve OS when combined with targeted therapy. However, careful patient selection remains warranted, they concluded.

Noting that only a third of the 15,000-plus patients in the study had surgery, the authors of an accompanying editorial questioned whether failure to use cytoreductive nephrectomy has contributed to poor survival in mRCC.

"The overall rate of cytoreductive nephrectomy observed in the study is significantly lower than that reported from centers of excellence (58% to 85%)," wrote Ana M. Molina, MD, Jim Hu, MD, and David M. Nanus, MD, of Weill Cornell Medicine in New York City.

Acknowledging limitations of the database used for the study, the editorialists said, "The data do suggest that the number of patients with mRCC who undergo cytoreductive nephrectomy is lower in the general population than indicated. This fact is alarming when considering the other analysis performed on these data, which examined the difference in overall survival between patients who did and did not undergo cytoreductive nephrectomy."

The FDA has approved several targeted therapies for mRCC since 2005. Widespread use of targeted agents to treat mRCC, combined with evidence of declining use of cytoreductive nephrectomy, might have blurred the role and potential benefits of surgery in mRCC, Choueiri and colleagues pointed out in their introduction. Nonetheless, clinical guidelines continued to identify a role for cytoreductive nephrectomy in combination with targeted therapy.

Research objectives

To add to the current paucity of data on the topic, the authors sought to examine utilization of cytoreductive nephrectomy in combination with targeted therapy as compared with targeted therapy alone for primary mRCC. They searched the National Cancer Data Base (NCDB) and identified patients who received at least one targeted therapy for treatment of mRCC during 2006 to 2013. Patients who also underwent cytoreductive nephrectomy were identified by associated ICD codes.

The primary objective was to determine how often cytoreductive nephrectomy was used in combination with targeted therapy for primary mRCC. Second, the authors wanted to compare survival in patients who had surgery in addition to targeted therapy versus those treated with targeted therapy alone.

Analysis and outcomes across 15,000+ patients

The analysis comprised 15,390 patients, of whom 5,374 (35%) underwent cytoreductive nephrectomy. Utilization of cytoreductive nephrectomy varied little throughout the study period.

As compared with patients who received only targeted therapy, the surgery group 

  • was significantly younger
  • was significantly more likely to be white
  • had private insurance
  • were treated at an academic center
  • had Fuhrman grade ¾
  • had clinical stage T1 disease and N0 nodal status
  • had less comorbidity

Of 12,995 patients included in the survival analysis, 10,882 patients died. The mean time to death from any cause was 32.5 months with cytoreductive nephrectomy and 14.9 months without. The median values were 17.1 and 7.7 months with and without cytoreductive nephrectomy, respectively. The 1-, 2-, and 3-year OS was 62.7%, 39.1%, and 27.7% with surgery plus targeted therapy and 34.7%, 17.1%, and 9.8% with targeted therapy alone.

An analysis limited to patients who had surgery compared survival with respect to the timing of cytoreductive nephrectomy (88.4% before targeted therapy, 11.6% afterward). Patients who had surgery first had OS of 61.2%, 37.8%, and 26.6% at 1, 2, and 3 years. That compared with 73,3%, 48.1%, and 35.3% among patients who received targeted therapy before surgery.

By multivariable regression analysis, cytoreductive surgery conferred more than a 50% reduction in the hazard for death from any cause.

The study had some limitations, including its retrospective nature and the fact that the NCDB only includes Commission on Cancer-accredited hospitals.


Source: MedPage Today

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