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Complete surgical metastasectomy improves survival in late-stage renal cell carcinoma

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May 3, 2017

Patients with late-stage renal cell carcinoma who underwent complete surgical metastasectomy achieved longer OS than patients who underwent incomplete metastasectomy, according to a meta-analysis published in The Journal of Urology.

“The research found patients who had surgery to remove metastases were about half as likely to have died of their metastatic disease at every point in time after diagnosis,” Bradley C. Leibovich, MD, chair of the urology department at Mayo Clinic in Rochester, Minnesota, said in a press release.

Kidney cancer cases have escalated over the past 2 decades. The American Cancer Society estimates 63,990 new diagnoses and 14,400 deaths in 2017.

“With a lot of cancers, we know there’s a range of survival, but kidney cancer is notable for very significant variability in survival after finding spread of the disease, with some patients dying much sooner and some living much longer than expected,” Leibovich said.

No randomized clinical trials have evaluated the role of complete surgical metastasectomy in patients with late-stage renal cell carcinoma. Observational studies have shown a survival benefit with an aggressive surgical approach but may be limited by selection bias.

To compare the survival benefit of complete surgical metastasectomy with incomplete or no metastasectomy, Leibovich and colleagues performed a systematic review of data from eight cohort studies with a low or moderate potential for bias.

The analysis included only comparative studies that reported adjusted HRs for all-cause mortality of incomplete surgical metastasectomy vs. complete surgical metastasectomy. The researchers used the Newcastle-Ottawa Scale to assess risk for bias.

Median OS served as the primary endpoint.

The analysis included 2,267 patients, 958 of whom underwent complete surgical metastasectomy and 1,309 who had incomplete surgical metastasectomy.

Median OS ranged from 36.5 months to 142 months for those who underwent complete surgical metastasectomy compared with 8.4 months to 27 months for incomplete surgical metastasectomy (adjusted HR = 2.37; 95% CI, 2.03-2.87) with low heterogeneity (I2 = 0%).

Complete surgical metastasectomy remained independently associated with a reduction in mortality across a priori subgroup and sensitivity analyses, regardless of adjusted performance status.

With more than 10 renal cell carcinoma treatments approved by the FDA in the past 10 years, future research should address the interaction of complete surgical metastasectomy and treatments to determine if the combination further increases survival, according to Leibovich.

“In people who haven’t had complete removal of the metastases, drug therapy seems to benefit,” Leibovich said. “But in patients who have that surgery, drug therapy doesn’t seem to make a difference. ... If the drugs work for only a finite period, and if surgery can lengthen the time before we need to enter that period, then we think that’s potentially additive to OS.” – by Chuck Gormley

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Disclosure: NIH funded this study. The researchers report no relevant financial disclosures.

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PERSPECTIVE
Derek Raghavan, MD, PhD

Derek Raghavan

I find it surprising that this paper was published in Journal of Urology as a CME–accredited paper. The researchers claim they have attempted stringently to overcome bias in the selection of the cases for inclusion in this series. Even at a glance — and I read the paper and several supporting papers carefully — it is clear there is huge case selection or ascertainment bias, despite the honorable intent to clean up the series being evaluated. Irrespective of the statistical tricks that the researchers have used to overcome bias, the critically important bias is the unwritten influence in the management of each case due to clinical impression — namely, a surgeon considering resection of metastases will carefully consider his feelings about the patient’s robustness and ability to withstand major surgery in the face of extant life-threatening disease and sometimes prior, tough systemic therapy. The vast majority of cases considered for multiple metastasectomies had pulmonary involvement. Although it is reasonable to contend that this paper showed even distribution of benefit across different risk groups, the reality is that the researchers of most of the individual papers — and of this overview analysis — cannot really show that the choice to proceed with metastasectomy is anything more than a selection of the fittest patients most likely to withstand the rigors of surgery; thus, there is a conflation of the impact of metastasectomy with innate characteristics of each patient as perceived by the surgeon who considers the procedure. In addition, in their attempt to clean up their meta-analysis, the researchers have cited a tiny proportion of the cases reported in the literature, without actually having avoided the key bias. Surgeons who wish to claim benefit from their innovative work should subject their hypotheses to the same rigor as those who test novel systemic therapies — in other words, proving the point after exploratory phase 1 and phase 2 trials by conducting well-designed phase 3 studies. However, that would require them to admit fallibility and uncertainty!


Derek Raghavan, MD, PhD

HemOnc Today Chief Medical Editor for Oncology

Levine Cancer Institute

Carolinas HealthCare System

Disclosure: Raghavan reports no relevant financial disclosures.