Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype. Available research describes its frequency across age and demographic groups, recurring chromosome and gene alterations, and outcomes reported in clinical trials of advanced renal cell carcinoma treatments. The figures below retain each study’s population, comparison, and measurement context.
Contents
- How common ccRCC is
- Incidence patterns in United States data
- Chromosome-level findings
- Genes and molecular subtypes
- Tumor evolution and study populations
- Treatment outcomes in first-line studies
- Later-line and historical treatment outcomes
How common ccRCC is
The National Cancer Institute (NCI) Clear Cell Renal Cell Carcinoma page reports that ccRCC makes up about 80% of all renal cell carcinoma cases. The same NCI source reports that ccRCC represents 2% to 6% of childhood and young adult kidney cancer cases. These percentages describe the subtype’s share within kidney cancer populations, not a person’s individual risk.
The NCI Clear Cell Renal Cell Carcinoma Study page gives a higher proportion for a particular genomic research population: approximately 92% of analyzed renal cell carcinoma cases in The Cancer Genome Atlas (TCGA) were clear cell carcinoma. The difference between about 80% and approximately 92% reflects different source populations and study contexts.
That NCI study page estimated that 58,240 Americans were expected to be diagnosed with kidney cancer in 2010 and that 13,040 Americans were expected to die of kidney cancer in 2010. These are 2010 United States estimates and are not current forecasts. They concern kidney cancer overall rather than ccRCC alone.
Incidence patterns in United States data
A SEER analysis titled Frequency, incidence and survival outcomes of clear cell renal cell carcinoma in the United States from 1973 to 2014 found that ccRCC incidence was 1.94 times higher in males than in females. In the same analysis, the incidence comparison for Whites, Blacks, and others was 1:0.79:0.91. This ratio is a relative comparison within that SEER analysis, not a percentage distribution.
The SEER analysis also reported a right-to-left incidence ratio of 1:0.96. In other words, the recorded incidence on the right side was compared with the left side using that ratio. Incidence peaked among people aged 60 to 79 years in the analysis.
These findings describe patterns in United States SEER data collected from 1973 through 2014. They should be read as population-level observations from that measurement period, rather than as a forecast of incidence in a later year or as an explanation of why the differences occurred.
Chromosome-level findings
The study Genomic copy number alterations in clear cell renal carcinoma reported 763 ccRCC patients. Of those patients, 412 provided frozen biopsies, equal to 54% of the 763-patient group. The copy-number findings below come from that study population.
| Copy-number finding | Reported share of ccRCC cases |
|---|---|
| 3p loss | 92.2% |
| 5q gain | 60.2% |
| 14q loss | 46.8% |
| 7q gain | 39.6% |
| 8p loss | 38.1% |
| 4q loss | 35.4% |
| 9p loss | 32.3% |
| 9q loss | 31.8% |
| 7p gain | 30.6% |
| 6q loss | 30.8% |
Additional losses reported in the same study were 3q loss in 29.4% of cases, 10q loss in 25.7%, 13q loss in 24.5%, and 1p loss in 23.5%. Additional gains were 5p gain in 26.5%, 20q gain in 25.5%, 12q gain in 24.8%, and 12p gain in 22.8%.
Another review, Chromosome 3p Loss-Orchestrated VHL, HIF, and Epigenetic Deregulation in Clear Cell Renal Cell Carcinoma, reports that chromosome 3p loss occurs in more than 90% of sporadic ccRCCs. The two 3p figures come from different reported sources: 92.2% in the copy-number study and more than 90% in the review’s description of sporadic disease.
Genes and molecular subtypes
The same chromosome 3p review reports that VHL is altered in about 80% of ccRCC. It gives alteration ranges of 29% to 46% for PBRM1, 6% to 19% for BAP1, and 8% to 30% for SETD2. These ranges indicate variation among cited studies and should not be treated as a single universal rate.
The paper Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma reports that biallelic VHL defects occur in approximately 75% of sporadic clear-cell RCC. A separate study, Mutational profile of primary clear cell renal cell carcinoma predicts recurrence and potential candidacy for adjuvant immune checkpoint inhibition, reported mutations in 51% of primary ccRCC tumors for VHL, 27% for PBRM1, 13% for BAP1, and 13% for SETD2. In that study, KDM5C, ATM, and MTOR were each mutated in 5% of primary tumors, while PTEN was mutated in 3%.
The results differ because the sources describe different measures and study populations: altered genes, biallelic defects, or mutations in a particular primary-tumor series. A percentage from one study cannot be used to calculate an individual patient’s genetic result.
In Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma, targeted next-generation sequencing analyzed 83 ccRCC samples. In that series, loss of nuclear PBRM1 expression was seen in 68% of samples, loss of BAP1 expression in 40%, and loss of H3K36me3 expression in 47%. These are expression findings in that 83-sample series, not interchangeable with mutation frequencies from other studies.
Tumor evolution and study populations
The multiregion sequencing study Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing sampled 10 individuals with ccRCC. Its tumors included 2 stage T2 tumors, 7 stage T3 tumors, and 1 stage T4 tumor. The study identified 73% to 75% of ccRCC driver aberrations as subclonal.
The sample structure matters when interpreting that 73% to 75% finding: it came from multiregion analysis in 10 individuals and from tumors distributed across the reported T2, T3, and T4 stages. It is a measurement of tumor evolution in that research group, not a population-wide percentage for every ccRCC diagnosis.
Another genomic study, Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma, found PBRM1 truncating mutations in 41% of 227 ccRCC cases. This 227-case result and the 83-sample expression study use different endpoints and sample sizes, so their percentages should be kept separate.
The chromosome 3p review reports a 5-year survival rate of 10% to 20% for metastatic ccRCC. That is a survival range for metastatic disease described in the review, not a survival estimate for localized ccRCC and not a prediction for an individual patient.
Treatment outcomes in first-line studies
The following trial results are reported in FDA labels. They describe the enrolled study populations and their stated comparison arms; they do not establish that one result applies to every person with ccRCC.
In CLEAR, 355 patients received lenvatinib plus pembrolizumab and 357 received sunitinib. Median progression-free survival (PFS) was 23.9 months versus 9.2 months, with a PFS hazard ratio of 0.39. Deaths occurred in 80 patients (23%) versus 101 patients (28%), and median overall survival (OS) was not reached in either arm at the data cutoff. The OS hazard ratio was 0.66. Confirmed objective response rate (ORR) was 71% versus 36%; complete response was 16% versus 4%, and partial response was 55% versus 32%.
KEYNOTE-426 enrolled 432 patients on pembrolizumab plus axitinib and 429 on sunitinib. At the reported cutoff, deaths occurred in 59 patients (14%) versus 97 patients (23%). The 12-month OS rate was 90% versus 78%, and median PFS was 15.1 versus 11.0 months. ORR was 59% versus 36%, including complete response rates of 6% versus 2% and partial response rates of 53% versus 34%.
CHECKMATE-9ER enrolled 323 patients on nivolumab plus cabozantinib and 328 on sunitinib. Median PFS was 16.6 versus 8.3 months, with a PFS hazard ratio of 0.51. Deaths occurred in 67 patients (21%) versus 99 patients (30%), and the OS hazard ratio was 0.60. Confirmed ORR was 55.7% versus 27.1%, including complete response rates of 8% versus 4.6% and partial response rates of 48% versus 23%. Median duration of response was 20.2 versus 11.5 months.
Later-line and historical treatment outcomes
FDA labeling for Study 205 reports 51 patients receiving lenvatinib plus everolimus and 50 receiving everolimus alone. Median PFS was 14.6 versus 5.5 months, with a PFS hazard ratio of 0.37. Median OS was 25.5 versus 15.4 months, with an OS hazard ratio of 0.67. Confirmed ORR was 37% versus 6%; complete response was 2% versus 0%, and partial response was 35% versus 6%.
FDA SUTENT labeling reports two studies in cytokine-refractory RCC. Study 4 enrolled 106 patients and reported an ORR of 34.0%; its median duration of response was not reached. Study 5 enrolled 63 patients and reported an ORR of 36.5%, with a median duration of response of 54 weeks.
The Study 205 and SUTENT figures come from their respective labeled study populations and treatment settings. Median duration of response reported as “not reached” is different from a measured number of weeks or months; it means the stated median had not been reached at the relevant analysis.