Perform genomic profiling in small renal masses to assess risk
Key Takeaways
A single biopsy with genomic characterization may be feasible in small renal tumors (less than 4 cm) that are candidates for active surveillance, according to study results presented here at the Sixteenth International Kidney Cancer Symposium, in Miami, FL.
Based on previous studies, renal cancer has been believed to have tumor heterogeneity. These previous studies, however, have been based on findings in large invasive metastatic tumors that were surgically removed.
Small renal tumors now comprise nearly one-half of all newly diagnosed renal masses, according to epidemiological studies, that are primarily based on incidental diagnosis during abdominal imaging.
“The incidence of kidney cancer is four times higher than it previously was, and a lot of that is due to incidental detection. The majority of these tumors that we are finding are generally between 2 to 4 cm, and many are destined to not cause harm. Many patients die with the tumor, rather than from the tumor,” explained lead researcher Brian M. Shuch, MD, assistant professor of urology and radiology, Yale School of Medicine, New Haven, CT. “Our study was designed to understand the genomic heterogeneity of those multiple regions in the small tumors versus large tumors. “
He added that at Yale, they have implented a clinical protocol to facilitate active surveillance and non-operative interventions in patients. Tumors are biopsied to better understand the genomic profile.
“The one criticism we have had is that people have said, citing the prior studies—one in New England Journal of Medicine and the other one in Nature Genetics—that a single biopsy is insufficient to characterize the complexity of the tumor,” said Dr. Shuch. “We would argue that we don’t know because it hasn’t been done in small renal tumors.”
For this study, Dr. Shuch and colleagues included 100 consecutive patients in whom they performed partial radical nephrectomy. Those deemed to be small tumors (less than 4 cm and clinical T1A) were compared to large tumors (greater than 7 cm and T2 or greater).
Upon excision, three to five separate regions of the tumor were captured and snap frozen for later analysis. He reported that their initial analysis of copy number events in small tumors were much less genetically complex, with fewer driver alterations. In addition, when assessing subclonal or shared regions, Dr. Shuch and fellow researchers found that genetic changes were generally shared throughout the small tumors. In large tumors, however, they found three to four times greater numbers of subclonal events.
In studying their genomic profiles for transcriptomic signaling and cell cycle progression scores, which are mRNA-based signatures, they also found greater correlation between all regions in small tumors. The correlation of these genes was very similar in small tumors, with over 90% correlation between all regions.
“And if you compare the genomic and transcriptomic signatures together, you clearly see that the tumors [that] are very heterogeneous in terms of their transcriptomic signature had a lot of subclonal events,” added Dr Shuch.
“As we move forward to do a biomarker-driven approach where we would actually define risk and dictate the treatment based on the genomic risk, this type of profiling prior to treatment seems very feasible and heterogeneity does not seem to be a barrier for this group of patients,” he concluded.