The validation cohort, the second cohort, included 257 patients: 177 primary tumors and 80 metastases. Analysis of these tumors showed no difference in the frequency of mutations or mutational burden between primary and metastatic tumors. In the second cohort the researchers also compared the frequency of gene mutations in primary tumors in patients who developed metastatic disease and those with localized disease; there was no difference in mutational frequency observed.
According to Dr McGregor, while these results are neither good nor bad news for patients, they are important. This study did not look at paired biopsies from primary tumors and metastases in the same patient, meaning that they do not provide information on how the same tumor may evolve. In addition, the study does not show how RCC treatments may affect genomic alterations of tumors.
For example, in a study published last year, Dr McGregor and colleagues looked at changes in the genomic profile of metastatic RCC from prior to first-line therapy to post-first-line therapy and found that the majority of patients had “clinically and biologically relevant genomics alterations.”3
Instead the study simply demonstrates that there was no identifiable mutation that allowed the RCC tumor to metastasize.
“If we had seen that only certain genes were altered in metastatic sites that weren’t altered in the primary site we may have been able to say that there was a potential target we could look at to help treat it more effectively,” Dr McGregor
- de Velasco G, Wankowicz SA, Madison R, et al. Targeted genomic landscape of metastases compared to primary tumours in clear cell metastatic renal cell carcinoma [published online April 20, 2018]. British Journal of Cancer. doi: 10.1038/s41416-018-0064-3
- Stankiewicz E, Mao X, Mangham DC, et al. Identification of FBXL4 as a metastasis associated gene in prostate cancer. Sci Rep. 2017;7:5124. doi: 10.1038/s41598-017-05209-z
- Pal SK, Sonpavde G, Agarwal N, et al. Evolution of circulating tumor DNA profile from first-line to subsequent therapy in metastatic renal cell carcinoma. Eur Urol. 2017;72:557-564. doi: 10.1016/j.eururo.2017.03.046