Related Experiment Video
Updated: Dec 20, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell
Carlotta Palumbo1, Elio Mazzone2, Francesco A Mistretta3
1Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Urology Unit, ASST Spedali Civili of Brescia, Department of Medical and Surgical Specialties, Radiological Science and Public Health, University of Brescia, Brescia, Italy.
Background:
Tyrosine kinase inhibitor-based adjuvant therapy showed no survival benefits for patients with high-risk nonmetastatic renal cell carcinoma (nmRCC). Five randomized immune-oncology checkpoint inhibitor trials are ongoing. We assessed the effect of stage, grade, and histologic type on cancer-specific mortality (CSM) in candidates for 1 of the 4 North American ongoing immune-oncology checkpoint inhibitor trials of high-risk nmRCC.
Patients And Methods:
From the Surveillance, Epidemiology, and End Results database (2001-2015), we identified patients who had undergone surgery for nmRCC and had met the inclusion criteria for the PROSPER RCC (nivolumab in treating patients with localized kidney cancer undergoing nephrectomy), CheckMate 914 (a study comparing the combination of nivolumab and ipilimumab versus placebo in participants with localized renal cell carcinoma), KEYNOTE-564 [safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy], or IMmotion010 [a study of atezolizumab as adjuvant therapy in participants with renal cell carcinoma (RCC) at high risk of developing metastasis following nephrectomy] trials. Kaplan-Meier and multivariable Cox regression models were used to assess the 10-year CSM rates in the overall cohort according to stage, grade, and histologic characteristics, and in 4 generated random samples according to the eligible patients for each of the 4 trials.
Results:
Of 116,750 patients who had undergone surgery for nmRCC, 18,559 (15.9%) had fulfilled the inclusion criteria for 1 of the 4 trials. The greatest proportion of higher stage and grade combinations and sarcomatoid histologic features would have qualified for IMmotion010, followed by KEYNOTE-564, CheckMate 914, and PROSPER RCC. Multivariable Cox regression models demonstrated the most unfavorable prognosis for stage N1 grade 3/4 (hazard ratio [HR], 11.5; P < .001), stage T4N0 grade 3/4 (HR, 9.8; P < .001), and sarcomatoid histologic features (HR, 5.5; P < .001). Among the 4 random samples, the difference in the qualifying criteria resulted in the greatest versus progressively lower CSM rates in the IMmotion010, KEYNOTE-564, CheckMate 914, and PROSPER RCC trials, respectively (P < .001).
Conclusions:
Our findings indicate that participation in adjuvant immunotherapy trials should be predominantly encouraged for patients with high-grade stage T3, T4, and N1 and patients with any stage with sarcomatoid pathologic features.
Insights
Adjuvant immunotherapy trials for high-risk nonmetastatic renal cell carcinoma (nmRCC) are ongoing. Patients with high-grade stage T3, T4, N1, or sarcomatoid features benefit most from these trials.
Area of Science:
- Urology
- Oncology
- Clinical Trials
Background:
- Adjuvant tyrosine kinase inhibitor therapy offers no survival benefit for high-risk nonmetastatic renal cell carcinoma (nmRCC).
- Several randomized immune-oncology checkpoint inhibitor trials are underway for nmRCC.
- This study evaluates prognostic factors for cancer-specific mortality (CSM) in nmRCC patients eligible for these trials.
Purpose of the Study:
- To assess the impact of tumor stage, grade, and histology on CSM in high-risk nmRCC.
- To identify patient subgroups most likely to benefit from adjuvant immunotherapy clinical trials.
Main Methods:
- Utilized the Surveillance, Epidemiology, and End Results database (2001-2015) for nmRCC patients meeting inclusion criteria for four major adjuvant immunotherapy trials.
- Employed Kaplan-Meier and multivariable Cox regression models to analyze 10-year CSM rates.
- Generated random samples to simulate patient eligibility for each specific trial.
Main Results:
- 15.9% of 116,750 surgically treated nmRCC patients met trial inclusion criteria.
- IMmotion010 trial had the highest proportion of patients with advanced stage, high grade, and sarcomatoid features.
- Multivariable analysis identified stage N1 grade 3/4 (HR 11.5), stage T4N0 grade 3/4 (HR 9.8), and sarcomatoid features (HR 5.5) as indicators of unfavorable prognosis.
- CSM rates varied significantly across the four trial cohorts, with IMmotion010 showing the highest rates.
Conclusions:
- Patients with high-grade stage T3, T4, N1 nmRCC, or any stage with sarcomatoid features, should be prioritized for adjuvant immunotherapy trials.
- These findings help stratify patients for optimal participation in ongoing clinical trials.
More Related Videos
Related Concept Videos
01:21Cancer Survival Analysis
01:27Tumor Immunotherapy