Diagnosis and treatment of upper tract urothelial carcinoma

Introduction Upper tract urothelial carcinoma (UTUC) is an uncommon disease with little evidence-based data to guide clinical decision-making. Recently, the tools available for the diagnosis and management of UTUC have improved significantly, complementing a growing understanding of the biology of this disease. Upper tract urothelial carcinoma requires appropriate management at all stages, since both the cure rate and morbidity are very sensitive to nuances of treatment. Yet proper risk stratification remains a challenge owing to the difficulty of clinical staging. This chapter presents a compact overview on diagnosis and treatment of UTUC. Contents The chapter is divided in two main sections. The first deals with diagnosis of UTUC focusing on the symptoms, imaging and specimen acquisition. We address contemporary concepts and controversies, including the timely and accurate diagnosis of UTUC and the integration of pathologic and radiographic variables for appropriate risk stratification. In addition, we discuss the natural history of UTUC, the role of imaging and endoscopy in clinical decision-making, diagnosis, staging and follow-up. Up-to-date information regarding clinical staging of UTUC, boundaries of surgical resection, indications for and extent of lymphadenectomy, and the role of perioperative chemotherapy in patients with high risk UTUC are discussed. Recommendations are discussed for diagnosis, as well as radical and conservative treatment. Conclusion Diagnosis of UTUC is based on the initial symptoms, which most frequently presenting as hematuria, as well as imaging, based on CT or MRI scan and cystoscopy, to exclude concomitant bladder cancer. To verify the diagnosis of UTUC, an ureteropyeloscopy is performed, which offers the opportunity to biopsy encountered lesions for pathological confirmation. Biomarkers can contribute to the diagnosis, also. The standard treatment for nonmetastatic high grade UTUC with anticipated adequate renal functional reserve is open or laparoscopic radical nephrectomy, with complete distal ureterectomy with a bladder cuff. Lymphadenectomy, discussed here, is recommended for adequate tumor staging and possibly improves survival. Endoscopic therapeutic procedures are indicated in well-selected patients with low risk disease; a segmental resection of the ureter can be considered for tumors located in that part of the upper tract, when nephron sparing is indicated or if tumors cannot be removed by endoscopic means. Adjuvant chemotherapy mat be considered for patients with high risk UTUC. Based on encouraging preliminary results, one can consider neoadjuvant chemotherapy to improve outcomes for well-selected, carefully-staged patients.