Cytoreductive Nephrectomy Benefits Some Kidney Cancer Patients

Roxanne Nelson

February 03, 2014

SAN FRANCISCO — Cytoreductive nephrectomy (CN) has been a popular surgical option for patients with renal cell carcinoma (RCC), but its role in the era of targeted therapies has become unclear. However, a new study demonstrates that CN extends overall survival even when targeted therapies are used, but that not all patients derive the same benefit.

Those who stand to gain the most benefit are patients with synchronous metastases from RCC who have a longer life expectancy, said lead author Daniel Heng, MD, MPH, clinical associate professor and staff medical oncologist at the University of Calgary in Alberta, Canada.

Patients with 4 or more factors on the International Metastatic RCC Database Consortium (IMDC) prognostic model and limited life expectancy should probably not receive CN, he explained. Physicians should use "IMDC prognostic criteria to predict whether patients will gain benefit from cytoreductive nephrectomy," he told Medscape Medical News.

"If it looks like they will gain a month or less, with the recovery time factored in, you probably will decrease their quality of life and subject them to a procedure that, in the end, will offer little benefit to them," he noted. "Patients with long expected survival — less than 4 IMDC criteria — are expected to benefit the most."

Dr. Heng presented the results here at the 2014 Genitourinary Cancers Symposium.

Unclear in Targeted Therapy Era

Before the advent of targeted therapies, CN had a clear role in metastatic RCC, Dr. Heng explained. It became a popular surgical option after the publication of data in 2001 from 2 prospective randomized trials: one by the Southwest Oncology Group (SWOG) and the other by the European Organization for Research and Treatment of Cancer (EORTC). The use of this procedure increased from 41% of kidney cancer patients in 2000 to 49% in 2005.

Now that targeted therapy is being used increasingly in RCC, the role of CN has become unclear, Dr. Heng explained.

In the interferon era, research demonstrated a benefit for CN in patients with metastatic disease. In a combined analysis of the SWOG 8949 and EORTC 30947 trials, survival benefit was 5.8 months for those who received CN in addition to interferon therapy (P = .002).

In their study, Dr. Heng and colleagues examined whether this survival benefit would still be seen with targeted therapies.

The initial patient population consisted of 3245 metastatic RCC patients. Of the 2569 (79%) who had undergone nephrectomy, the 1587 patients who had undergone the procedure before their diagnosis of metastatic disease were excluded from the analysis.

Of the remaining patients, 982 (59%) had undergone CN and 676 (41%) had not. All received targeted therapy — the majority (72%) received first-line sunitinib, 15% received sorafenib, 5% received temsirolimus, 3% received bevacizumab, and 3% received pazopanib.

Most Benefit with Longer Survival Time

Median overall survival was better for patients who underwent CN than for those who did not (20.6 vs 9.5 months; P < .0001). When the data were adjusted for IMDC criteria to correct for imbalances, the hazard ratio for death was 0.60 (95% confidence interval, 0.52 - 0.69; P < .0001). The IMDC prognostic factors included a Karnofsky performance score below 80%, a diagnosis-to-treatment interval of less than 1 year, anemia, thrombocytosis, neutrophilia, and hypercalcemia.

The researchers found that the survival benefit of CN was better if the patient had a longer survival time.

Table 1. Incremental Survival Benefit With CN

Overall Survival (Months) Incremental Survival Benefit (Months) P Value
<24 5.2 <.0001
<18 3.3 <.0001
<12 2.2 <.0001
<9 1.0 .0027
<6 0.8 .0084
<3 0.1 .9429

 

Dr. Heng explained that CN can be beneficial in this population even after adjustment for prognostic factors, but patients whose survival was estimated to be less than 9 to 12 months had a marginal benefit, compared with those with longer estimated survival.

Table 2. Diminishing Benefit of CN With More Prognostic Factors

IMDC Prognostic Factors (n) Survival With CN (Months) Survival Without CN (Months) P Value
1 30.4 22.5 <.024
4 6.0 5.4 .1664

 

This study shows that CN appears to improve survival, but not all patient should receive it, said study discussant Daniel Canter, MD, from the Fox Chase Cancer Center in Philadelphia.

However, he noted, questions remain, particularly about the need for risk groups to be redefined. He suggested that there is "room for further refinement with this model."

He also pointed out that more data are needed on surgical complication rates.

Dr. Heng reports consulting and/or serving on advisory boards for Aveo, Bayer, BMS, Pfizer, and Novartis.

2014 Genitourinary Cancers Symposium (GUCS). Abstract 396. Presented February 1, 2014.

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