Evidence date · 2021-05-08 · Research note 1 of 3
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Among people with metastatic renal cell carcinoma—a form of kidney cancer that has spread beyond the kidney—removing the primary tumor was more strongly associated with overall survival in immunotherapy cohorts than in targeted-therapy cohorts. That was the central finding of a systematic review published May 8, 2021. The comparison raises a useful question: whether the treatment given alongside surgery changes how the observed survival association should be understood.
An operation in a changing treatment landscape
Cytoreductive nephrectomy means removing the primary kidney tumor when cancer has already spread. The operation had a role when paired with interferon after earlier trials reported a survival benefit. As systemic treatments changed, the authors asked whether the association between surgery and survival differed according to the treatment approach.
The review focused on targeted therapy and immunotherapy. These are different approaches to treating cancer throughout the body. The paper’s question was not simply whether surgery was associated with survival, but whether that association looked different across cohorts receiving these treatments.
How the review compared the cohorts
The authors systematically identified studies of cytoreductive nephrectomy in patients receiving targeted therapy or immunotherapy. They extracted multivariable-adjusted hazard ratios for overall survival, then combined estimates using a random-effects model. In everyday terms, the analysis summarized the surgery-associated survival estimates while allowing for variation among the studies.
The authors also tested whether the association differed by treatment approach. They compared the surgery-related hazard ratios between the targeted-therapy and immunotherapy groups. This test addresses a difference between observed associations; it does not make the underlying treatment groups equivalent or turn the comparison into a randomized test of surgery.
What the hazard ratios show
The authors identified three comparisons. The targeted-therapy pool included two cohorts and reported a hazard ratio of 0.52 (95% confidence interval 0.46–0.59; I² = 80%). The immunotherapy pool also included two cohorts and reported a hazard ratio of 0.28 (95% confidence interval 0.16–0.49; I² = 21%). The authors reported a stronger surgery–survival association in the immunotherapy group, with p = 0.01 for the comparison between treatment approaches.
A hazard ratio below 1 indicates a lower relative hazard of death associated with surgery, compared with patients who did not have the operation in those cohorts. The lower value in the immunotherapy pool therefore represents a stronger relative association than the value in the targeted-therapy pool. It is not a percentage of patients saved or an estimate of how many months an operation might add. The confidence intervals describe statistical uncertainty around the estimates.
The I² figures describe variation among the study estimates. At 80%, variation was greater in the targeted-therapy pool than in the immunotherapy pool, where I² was 21%. The pooled number for targeted therapy therefore summarizes results that differed considerably across its two cohorts; it should not be read as a single, uniform association across all patients or settings.
Why the comparison cannot decide who should have surgery
These estimates came from observational cohorts, not a new randomized trial assigning patients to kidney surgery or no surgery alongside immunotherapy. Statistical adjustment can account for measured differences included in the underlying studies, but it cannot rule out other differences that affected both who had surgery and how long people lived. Patient selection or residual confounding could contribute to the observed associations.
The comparison also cannot show that the drug approach caused the difference between the two pooled estimates. Each estimate summarizes surgery-associated outcomes within separate treatment cohorts; it does not compare otherwise identical patients receiving different drugs. The figures alone cannot establish an absolute survival gain, weigh the harms and tradeoffs of surgery, or identify which individual patients would benefit.
Where kidney surgery might fit alongside immunotherapy
If comparative evidence confirms which patients gain survival after accounting for selection into surgery and the operation’s tradeoffs, care teams could make better decisions about adding removal of the primary kidney tumor to immunotherapy for metastatic kidney cancer. That more specific treatment choice was a possibility to investigate from the 2021 perspective, not a conclusion this review could settle.
Key Sources
- Primary source: Association between cytoreductive nephrectomy and survival among patients with metastatic renal cell carcinoma receiving modern therapies: a systematic review and meta-analysis examining effect modification according to systemic therapy approach.
DOI or Journal Page · Review or Meta-Analysis · 2021-05-08