Liver metastases, compared with metastases at other anatomic sites, predict worse outcomes in patients treated with immune checkpoint inhibitors (ICIs) for advanced genitourinary (GU) cancers, according to a recent study.

In addition, patients who experience a greater frequency and higher grades of immune-related adverse effects (irAEs) are more likely to have better rates of response to ICI therapy, a finding consistent with other studies.

In a retrospective cohort study of 160 patients with metastatic or unresectable renal cell carcinoma (RCC, 88 patients) or urothelial carcinoma (UC, 72 patients) treated with ICIs, liver metastases were significantly associated with worse objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with other sites of metastasis.

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For the study population overall, the complete response rate to ICI therapy was 8.3%, but it varied by metastasis site: 0% for patients with liver metastases, 5.3% for those with lymph node metastases, 9.4% for those with central nervous system (CNS) and/or bone metastases, and 19.2% for those with lung and other metastases, Vincent T. Ma, MD, of the Division of Hematology and Oncology at the University of Michigan in Ann Arbor, Michigan, and colleagues reported in Urologic Oncology.

On multivariable analysis, liver metastases were significantly associated with approximately 3.0- 2.5-, and 2.5-fold increased risks for progression and 3.1-, 3.8-, and 2.0-fold increased risks for death compared with lymph node metastases only, lung metastases, and CNS and/or bone metastases, respectively.

In other findings, the study demonstrated that median PFS and OS were lower in the UC group compared with the RCC group (2.8 vs 5.0 months for PFS and 9.6 vs 23.6 months for OS, respectively). Increased frequency and higher grades of irAEs were significantly associated with better treatment ORR rate with ICI therapy. The proportion of patients with a complete response was 18.8% for those who experienced 2 or more irAEs compared with 5.2% and 4.8% of those who had 0 or 1 irAE, respectively, according to the investigators. The complete response rate was 18.8% among patients with an irAE grade toxicity of 3 or higher compared with a 5.2% rate for those with a grade toxicity of 0.

“Our study supports a growing body of literature suggesting the presence of irAEs as a good correlative marker of anti-tumor response to ICI across a variety of cancer types,” the authors wrote.

Overall, the study population had a median age of 65.6 years. The median ages in the RCC and UC groups were 61.3 and 70.9 years, respectively. The median follow-up duration was 10.8 months. In all, 70 patients received nivolumab, 53 received pembrolizumab, 24 received atezolizumab, and 13 combination ipilimumab/nivolumab.

“These findings may help to guide immunotherapy decisions in patients with advanced stage GU malignancies, although larger cohort studies are warranted to confirm our reported associations,” Dr Ma and colleagues concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Ma VT, Su CT, Hu M, et al. Characterization of outcomes in patients with advanced genitourinary malignancies treated with immune checkpoint inhibitors. Published online January 23, 2021. Urol Oncol. doi:10.10166/j.urolonc.2021.01.006