Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history

Abstract

Superficial "non-muscle-invasive" bladder tumors represent a heterogeneous group of cancers, including those that are (1) papillary in nature and limited to the mucosa, (2) high grade and flat and confined to the epithelium, and (3) invasive into the submucosa, or lamina propria. The goal of treatment is 2-fold: (1) to reduce tumor recurrence and the subsequent need for additional therapies and the morbidity associated with these treatments and (2) to prevent tumor progression and the subsequent need for more aggressive therapy. This update reviews important contemporary concepts in the etiology, molecular mechanisms, classification, and natural history of superficial bladder cancer.

Keywords: Bladder neoplasms; Genitourinary tumors; Molecular mechanisms; Non-muscle-invasive tumor; Transitional cell carcinoma.

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Figure 1

Model depicting potential pathways for urothelial tumorigenesis and progression. This model includes some key molecular events that occur during bladder tumorigenesis and demonstrates how the less aggressive papillary carcinomas generally differ in their origin from the more aggressive carcinoma in situ. Most papillary noninvasive carcinomas do not progress to an invasive phenotype but are more prone to recurrences. Those that do, however, usually accumulate more genetic abnormalities. *Activating mutations; †Inactivating mutations; FGFR3, fibroblast growth factor receptor 3; HRAS, transforming protein p21/H-RAS-1 (Harvey murine sarcoma virus oncogene).