Spectrum of tumor mutational load (TML) in genitourinary cancers (GU CA).

Abstract

4535 Background: Immunotherapy (IO) is now standard of care for bladder and kidney cancer (CA) and is investigational in other GU CA such as prostate and germ cell CA. Tumor mutational load (TML) has correlated with response to IO in several tumor types. Herein, we explore TML across different histological subtypes in GU CA. In addition, we also assess the correlation between TML and PD-L1 status. Methods: 544 GU specimens were identified: bladder, 145; kidney, 164; prostate, 221; penile, 2; testicular, 12. TML was calculated using somatic non-synonymous missense mutations from a 592-gene panel (Illumina NextSeq). A high TML was > 17 mutations/MB. PD-L1 (SP142) was done depending tumor availability. Results: High TML was more prevalent in bladder CA (14.5%, 21/145) compared to other GU CA. Urothelial carcinomas had a noticeably high TML while squamous histology had a pronounced PD-L1 expression (Figure 1). A comparison of TML-high (n=15) versus TML-low (n=76) urothelial bladder CA showed the following differences (Figure 2). TML was rare in kidney CA (1.8%, 1/57); PD-L1 was high in sarcomatoid (33.3%, 5/15), CDC/RMC (28.6%, 2/7). Prostate adenocarcinoma had few TML-high (2.3%, 5/219) or PD-L1 expressing tumors (1.4%, 3/208). Tumors of penile or testicular origin lacked high TML and PD-L1 expression. No correlation was found between a high TML and PD-L1 expression. Conclusions: TML varied considerably amongst GU CA. As in other CA, TML-high scores did not predict PD-L1 expression and vice versa. Comprehension of the underlying biology may assist in determining which CA may respond better to IO. [Table: see text] [Table: see text]