EAU 2018: PD-L1 Expression is Associated with Tumor Progression and Poor Prognosis in Xp11.2 Translocation Renal Cell Carcinoma

Copenhagen, Denmark (UroToday.com) Xp11.2 translocation renal cell carcinoma (RCC) is a recent subtype of RCC that often has a more aggressive clinical course. They often present in younger patients. They are characterized by various translocations involving chromosome Xp11.2, all resulting in gene fusions involving the transcription factor E3 (TFE3) gene. It is a relatively rare subtype, making large studies difficult.

As with all solid malignancies, there has been increasing focus on the immune checkpoint cascades, and their potential utility in treating these advanced cases. With an approximately 20-30% durable response rate seen in most cancers, they hold promise for a select group of patients. However, selecting those patients likely to benefit from this costly treatment has been more difficult. IHC expression of the primary targets has had mixed responses, depending on malignancy.

In this study, the authors assess a relatively large series of patients with Xp11.2 translocation renal cell carcinoma for PD-L1 IHC expression, and then correlate it to clinical outcomes. Immunohistochemistry was conducted on formalin-fixed paraffin-embedded (FFPE) specimens from 42 adult Xp11.2 RCC patients who were histologically confirmed by FISH analysis.

Among 42 assessed Xp11.2 RCC patients, 13 (31.0%) patients showed “high” expression of PD-L1 and 29 (69.0%) patients showed “low” PD-L1 expression. However, they never define high or low expression – which varies significantly based on antibody and study. In their figure, they link “high” with positive staining.

They then correlated PD-L1 expression with clinical characteristics, and found that high PD-L1 expression was correlated with the presence of advanced tumor stage (P=0.001), regional lymph node metastasis (P<0.001) and distant metastasis (P<0.001). In the multivariate analysis, N stage (HR: 4.206, P = 0.035), M stage (HR: 14.311, P = 0.009) and high PD-L1 expression (HR: 4.617, P = 0.006) were independent prognostic factors of worse progression-free survival (PFS). Moreover, high PD-L1 expression (HR: 6.463, P = 0.007), along with distant metastasis (HR: 9.203, P = 0.017), was independent prognostic factors for worse OS after adjusting for covariates. Unfortunately, the MV analysis was not provided for further evaluation . 

However, it should be noted that in other studies and other malignancies, PD-L1 expression was not associated with response to immune checkpoint inhibitors. So, while it may be a prognostic indicator, it is not yet established as a predictor of therapy response. 


Presented by: Z. Yiping

Co-Authors: Qu Y-Y., Chang K., Xaio W-J., Wang H-K., Zhang H-L., Ye D-W.
Author Information: Fudan University Shanghai Cancer Center, Dept. of Urology, Shanghai, China

Written by: Thenappan Chandrasekar, MD Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark