ASCO GU 2019: The UCLA Histo-Genetic Risk Classification (U-HGRC) to Predict Outcomes of Localized Clear Cell Renal Cell Carcinoma

San Francisco, CA (UroToday.com) Up to 30% of patients with clinically localized renal cell carcinoma (RCC) will eventually experience recurrence.  For this reason, multiple clinical trials with targeted agents have been performed to determine if adjuvant systemic therapy can reduce this risk in high-risk patients. While some trials suggested these agents did not confer any benefit, sunitinib is currently approved for adjuvant use in patients who are considered to be high-risk. There are several current risk stratification systems that are currently being used to help predict the risk of recurrence, however these systems may misclassify some patients. At the Localized Kidney Cancer Session at the 2019 Genitourinary Cancers Symposium in San Francisco, Dr. Cedric Michel Lebacle presented on the UCLA Histo-Genetic Risk Classification (U-HGRC) model, which is aimed at more accurately predicting an individual patient’s risk of recurrence of RCC after surgical resection.

He and his group evaluated 646 patients who underwent either nephron-sparing surgery or radical nephrectomy at UCLA for clinically-localized clear cell RCC who had tumor and cytogenetic analysis performed on their tissue post-operatively. Histopathologic features included in this analysis included T stage, tumor size, and presence of sarcomatoid features.  They found specific cytogenetic abnormalities, including gain of chromosome 5q, loss of chromosome 10q, and loss of X or Y chromosomes provided additional prognostic information.  Patients were stratified into U-HGRC groups 1 (low), 2 (intermediate), and 3 (high) based on the combination of their histopathologic and cytogenetic features.  At a median follow-up of 55 months, they found that a patient’s U-HGRC group was strongly correlated with individual recurrence risk, particularly for the high-risk group. The risk of recurrence at 5 years for group 1 was 9%, group 2 was 25%, and group 3 was 62% (median disease-free survival of 47 months).  These findings were then internally validated with two other random samples of patients and were again found to be statistically significant.

The U-HGRC model was also predictive of overall survival, with group 1 patients having a 4% risk of death at 5 years, group 2 patients having a 9% risk at 5 years, and the group 3 patients having a 22% risk of death at 5 years.  The addition of the cytogenetic information provided additional accuracy of recurrence prediction over prior models that took into account histopathologic factors alone.

Dr. Lebacle concluded that the U-HGRC integrates cytologic alterations with clinical and pathologic features, and that this model allows for better risk-stratification of recurrence and overall survival over prior models.  He believes that more accurate prognostication could help to better identify those patients who may benefit from enrollment into adjuvant clinical trials.

Presented by: Cedric Michel Lebacle, MD

Written by: Brian Kadow, MD. Society of Urologic Oncology Fellow, Fox Chase Cancer Center at the Annual ASCO GU meeting 2019, San Francisco, CA, Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA