Angiogenesis, Lymphangiogenesis and Lymphovascular Invasion: Prognostic Impact for Bladder Cancer Patients

Bladder cancer is the second most common tumor of the urogenital tract. Urothelial carcinoma is the most frequent histologic type, being unique among epithelial carcinomas in its divergent pathways of tumorigenesis. Surgery continues to have a predominant role in the management of urothelial bladder cancer (Kaufman et al., 2009). However, the debate about the best treatment approach for T1G3 and muscle invasive tumors continually challenges all urologic surgeons and oncologists. This debate involves several aspects. First, a significant number of T1G3 tumors recurs and progresses rapidly after transurethral resection and BCG treatment (Wiesner et al., 2005). Second, half of patients with invasive tumors have a dismal outcome despite an effective treatment by radical cystectomy (Sternberg et al., 2007). Third, the extension of lymphadenectomy remains an issue of controversy, although clinical evidence suggests that an extended lymph node dissection may not only provide prognostic information, but also a significant therapeutic benefit for both lymph node-positive and lymph node-negative patients undergoing radical cystectomy (May et al., 2011). In muscle invasive bladder cancer, the presence of tumor foci in lymph nodes is an early event in progression, and the lymphatic vessels within or in the proximity to the primary tumor serve as the primary conduits for tumor dissemination (Youssef et al., 2011). Fourth, although urothelial bladder cancer is a chemo-sensitive tumor (Kaufman et al., 2000; von der Maase et al., 2000), adjuvant systemic chemotherapy does not reveal benefits (Walz et al., 2008), and neoadjuvant chemotherapy is not yet accepted as the best approach in invasive bladder cancer (Clark, 2009). Therefore, in order to solve the aforementioned problems, it is crucial to improve the knowledge about tumor microenvironment, regulation of cancer metabolism and neovascularization.