SAN FRANCISCO – Only selected patients with synchronous metastases from renal cell carcinoma derive a survival benefit from a cytoreductive nephrectomy, a retrospective cohort study showed.
Researchers studied more than 1,600 patients from the International mRCC (metastatic renal cell carcinoma) Database Consortium who developed metastases while their primary tumor was still in place.
Dr. Daniel Heng
The main analyses showed that as a whole, patients who underwent cytoreductive nephrectomy lived longer than their counterparts who did not have this surgery.
However, in stratified analyses, the surgery significantly prolonged survival only among patients who had a life expectancy exceeding 12 months and patients who had three or fewer risk factors by International mRCC Database Consortium (IMDC) criteria.
Risk factors include Karnofsky performance status less than 80%, an interval between diagnosis and treatment of less than 1 year, anemia, thrombocytosis, neutrophilia, and hypercalcemia
"Overall, I think we can say that cytoreductive nephrectomy may be beneficial in the age of targeted therapy. However, not all patients should have it," commented first author Dr. Daniel Y.C. Heng of the University of Calgary (Alta.).
"Patients with four or more IMDC risk factors and patients with limited life expectancy probably shouldn’t have a cytoreductive nephrectomy," he said. "Of course, there are probably exceptions to that rule; if patients are really symptomatic in the primary, for example, or have bleeding, maybe there are exceptions.
"But I think this is a very interesting and useful way to help select our patients for cytoreductive nephrectomy. Certainly, we are awaiting the CARMENA and SURTIME phase III randomized controlled trials to prospectively evaluate this, and hopefully, we will be able to look at the IMDC risk factors to see if they can aid in patient selection in a prospectively validated way," Dr. Heng said at the 2014 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.
Cytoreductive nephrectomy carries risks of morbidity and mortality, and some patients may be unable to go on to receive systemic therapy, noted invited discussant Dr. Daniel Canter of the Fox Chase Cancer Center, Philadelphia.
"What I take home as the most important point of this talk is that we need to make better choices and risk stratify these patients before surgery," he said.
A key question arising from the new data is whether the IMDC risk groups should be redefined, according to Dr. Canter; for example, patients with three risk factors are currently placed in the poor risk group, yet they derived significant benefit from surgery in this study. "So is there room for further refinement in this model?" he asked.
"With such a large cohort, I think that adding to this data with complication rates and perioperative mortality would certainly be important in terms of future treatment decision making," he commented.
Session attendee Dr. Adam Metwalli of the National Cancer Institute asked, "Are there specific risk factors that seem to disproportionately cluster among those who have four or five that would help to distinguish them from the ones who have zero to three?"
"By far, the most important prognostic factor is Karnofsky performance status, and that makes sense," Dr. Heng replied. "It’s partially the ‘look test’ and how you think a patient will fare. So, that by far has the biggest contribution."
Introducing the study, he noted that cytoreductive nephrectomy has previously been found to prolong survival by about 6 months in patients with metastatic renal cell carcinoma treated in the immunotherapy era.
"But of course now we are in the age of targeted therapy, with VEGF [vascular endothelial growth factor] inhibitors and mTOR [mammalian target of rapamycin] inhibitors. These are drugs that are much more active than in the era of old immunotherapy. So it begs the question, is cytoreductive nephrectomy still relevant?" Dr. Heng said.
The researchers studied 1,658 patients from 20 institutions who had mRCC with synchronous metastases, of whom 59% underwent cytoreductive nephrectomy.
They had a median age of 59 years, and about half were in the IMDC intermediate-risk group. The most common prior targeted therapy was sunitinib (Sutent), received by about three-fourths, reported Dr. Heng.
In unadjusted analyses, median overall survival was a significant 11 months longer for patients who underwent cytoreductive nephrectomy compared with their counterparts who did not (20.6 vs. 9.5 months). After adjustment for IMDC risk factors, the surgery was associated with a 40% reduction in the risk of death in the entire cohort (hazard ratio, 0.60; P less than .0001).
However, in analyses stratified by patient life expectancy, there was a significant survival benefit of cytoreductive nephrectomy only among patients expected to live 12-18 months (3.3-month incremental benefit; adjusted hazard ratio, 0.85; P = .049) or 18-24 months (5.2-month incremental benefit; adjusted hazard ratio, 0.72; P less than .0001).