Upper tract urothelial cancer (UTUC) genomic profiling and correlation regarding benefit of platinum-based chemotherapy

Abstract

Upper tract urothelial cancer (UTUC) are rare subsets of urothelial cancer, which typically present with more aggressive course. Molecular markers stratifying urothelial tumors as luminal subtype and non-luminal subtype tumors have been proposed to select patients who may have greater or lesser benefit from neoadjuvant systemic therapy in bladder cancer, though not yet evaluated in UTUC. Here, a single-institution study retrospectively obtained clinical and genomic information in patients with UTUC and evaluated four patient tumors using the Decipher Bladder^® assay and Foundation Medicine^® test. All four patients had non-luminal molecular subtype including basal (N = 4) and mixed basal/claudin-low (N = 2) subtypes. The best clinical response achieved was stable disease in a patient who had basal/claudin-low subtype with residual ypT3 after neoadjuvant chemotherapy. For the remaining three patients, all were treated with platinum-based chemotherapy for eventual metastatic disease but all three showed progressive disease with limited overall survival, highlighting their aggressive course. The non-luminal subtype and lack of FGFR alteration may partly explain the poor overall outcomes while the real-world benefit of next generation sequencing for clinical use in UTUC patients require further clarification in a larger cohort study.

Keywords: Decipher Bladder®; Upper tract urothelial cancers; molecular subtypes; neoadjuvant chemotherapy.

Figure 1

Bladder Decipher^® GRID. A. Pertains to clinical case 1; B. pertains to clinical case 2; C. pertains to clinical case 3; D. pertains to clinical case 4. Selected marker expression from the Bladder Decipher^® Grid which contains RNA expression values with the list of 48 genes grouped according to biological modules of luminal, basal, immune, epithelial-mesenchymal transition, stromal, and neuronal. The population rank refers to the percentage of tumor RNA profiles in the GRID Reference population. The bottom panel shows the genomic atlas or gene expression signatures that defines tumor biology

Figure 2

Pathological findings on H&E for clinical case 1. A. Clinical case 1 pathological staging ypT3 high grade urothelial carcinoma with glandular and focal squamous differentiation involving the renal pelvis (40× H&E); B. high grade urothelial carcinoma extending into peri pelvic adipose tissue (100× H&E)

Figure 3

Computed tomography (CT) scan findings of clinical case 2 with enlarging hilar mass at 30 mm × 37 mm size (arrows)

Figure 4

Pathologic findings on H&E for clinical case 3. A. Clinical case 3 pathological staging pT3 high grade papillary urothelial carcinoma of renal pelvis (40× H&E); B. high grade papillary urothelial carcinoma invades renal parenchyma (100× H&E)

Figure 5

Computed tomography (CT) scan of clinical case 3 showing liver metastases (red arrows) and largest size measuring 38 mm × 32.4 mm