Genitourinary malignancies represent heterogeneous group of diseases linked by anatomical and physiological function but different in almost every aspect of pathophysiology, molecular biology, prognosis and treatment of metastatic disease. Prostate cancer is by far the most common of genitourinary malignancies; it is characterized by relatively indolent behavior, propensity for bone metastases and reliance on androgen‑androgen receptor pathway that is exploited therapeutically with considerable success. Kidney cancer is probably one of the most unpredictable tumors, prototypical “internist’s disease” associated with multiple paraneoplastic, metabolic and hormonal syndromes that frequently accompany metastatic process. Renal carcinoma is driven by derangements in VEGF and mTOR pathways and compounds inhibiting signaling through these pathways bestow significant therapeutic benefit that improved the prognosis and outcomes in patients with metastatic disease. Testicular cancer is largely curable with cisplatin‑based combination chemotherapy and cures are common even in circumstances of widely disseminated disease with visceral multi‑organ involvement. This represents one of the remarkable achievements of modern oncology and somewhat of a mystery since the same therapy is not nearly as effective in any other solid tumor type.
Urothelial cancers unfortunately represent the subset of neoplasms with relatively limited progress in therapeutic options for metastatic disease although rare patients can be cured with combination chemotherapy especially in the setting of low volume metastases limited to lymph nodes or lungs. In this chapter we describe the basic aspects of biology and therapy of four most common cancers of genitourinary origin: kidney, prostate, bladder/urothelium and testicular germ cell tumors focusing on unique aspects of each disease and recent therapeutic advances.