Optimal Management of Upper Tract Urothelial Carcinoma: an Unmet Need
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Upper tract urothelial carcinoma (UTUC) is a rare genitourinary entity of the renal pelvis and the ureter characterized by a more aggressive disease phenotype when compared with urothelial carcinoma of the bladder (UCB) with more than half of UTUC cases presenting with invasive disease at diagnosis compared to 20% for bladder tumors. There is growing evidence suggesting that its distinct natural history from that of bladder cancer can be related to several genetic and epigenetic differences. Treatment of low-risk disease consists of kidney-sparing surgeries such as ureteroscopic and percutaneous treatments, segmental ureterectomy, and adjuvant topical and intracavitary chemo-immunotherapies. The standard of care for high-risk non-metastatic disease remains radical nephroureterectomy and bladder cuff excision with increasing utilization rates of minimally invasive approaches leading to reduced morbidity without compromising outcomes while the role of lymphadenectomy is still being investigated. The prognosis of UTUC has been stagnant over the past decade highlighting the need for further studies on the role of multimodal therapy (neoadjuvant/adjuvant chemotherapy, immunotherapy, targeted therapy) to optimize management and improve outcomes.
KeywordsUpper tract urothelial carcinoma Kidney-sparing surgery Radical nephroureterectomy Minimally invasive surgery Adjuvant chemo-immunotherapy Systemic therapy
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The authors declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 1.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.Google Scholar
- 4.••Sfakianos JP, Cha EK, Iyer G, Scott SN, Zabor EC, Shah RH, et al. Genomic characterization of upper tract urothelial carcinoma. Eur Urol. 2015;68(6):970–7. Using next-generation sequencing from 59 UTUC and 102 UCB patients, the authors identified similar mutations in both cancer types but at different frequencies indicating a potential need for unique management strategies.Google Scholar
- 6.•Campbell MT, Shah AY, Matin SF, Siefker-Radtke AO. Optimizing management of upper tract urothelial carcinoma. Urol Oncol. 2017;35(7):492–8.The authors present an interesting review of the current evidence for perioperative chemotherapy in UTUC as well as developments in the molecular classification of UTUC.Google Scholar
- 7.•Roupret M, Babjuk M, Comperat E, Zigeuner R, Sylvester RJ, Burger M, et al. European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2017 update. Eur Urol. 2018;73(1):111–22.This 2017 update of the EAU guidelines on UTUC offers a great overview of the present evidence-based recommendations for UTUC management.Google Scholar
- 9.•Seisen T, Peyronnet B, Dominguez-Escrig JL, Bruins HM, Yuan CY, Babjuk M, et al. Oncologic outcomes of kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel. Eur Urol. 2016;70(6):1052–68.In this systematic review by the EAU bladder cancer guidelines panel, the authors review the studies comparing kidney-sparing surgery vs. radical nephroureterectomy for UTC and found similar oncologic outcomes for low-risk tumors with ureteroscopic and percutaneous management. Selected patients with high-grade and invasive tumors could benefit from segmental ureterectomy.Google Scholar
- 15.Liu F, Guo W, Zhou X, Ding Y, Ma Y, Hou Y, et al. Laparoscopic versus open nephroureterectomy for upper urinary tract urothelial carcinoma: a systematic review and meta-analysis. Medicine (Baltimore). 2018;97(35):e11954.Google Scholar
- 19.Nazzani S, Preisser F, Mazzone E, Tian Z, Mistretta FA, Soulieres D, et al. Nephroureterectomy with or without bladder cuff excision for localized urothelial carcinoma of the renal pelvis. Eur Urol Focus. 2018.Google Scholar
- 22.•Matin SF, Sfakianos JP, Espiritu PN, Coleman JA, Spiess PE. Patterns of lymphatic metastases in upper tract urothelial carcinoma and proposed dissection templates. J Urol. 2015;194(6):1567–74.In this retrospective multi-institutional study from three NCI designated comprehensive cancer centers, the authors investigated the patterns of lymph node metastasis in 73 patients undergoing nephroureterectomy with lymphadenectomy and proposed a dissection templates according to laterality and location of the tumor within the upper urinary tract.Google Scholar
- 24.•Dominguez-Escrig JL, Peyronnet B, Seisen T, Bruins HM, Yuan CY, Babjuk M, et al. Potential benefit of lymph node dissection during radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review by the European Association of Urology Guidelines Panel on Non-muscle-invasive Bladder Cancer. Eur Urol Focus. 2017. https://doi.org/10.1016/j.euf.2017.09.015. In this systematic review by the EAU bladder cancer guidelines panel, the authors review the studies comparing nephrouretrectomy with or without lymphadenectomy and found that lymph node dissection improves survival in patients with high-stage renal pelvic tumors if performed in an anatomical template-based approach.
- 28.Novara G, De Marco V, Dalpiaz O, Galfano A, Bouygues V, Gardiman M, et al. Independent predictors of contralateral metachronous upper urinary tract transitional cell carcinoma after nephroureterectomy: multi-institutional dataset from three European centers. Int J Urol. 2009;16(2):187–91.PubMedGoogle Scholar
- 29.•Flaig TW, Spiess PE, Agarwal N, Bangs R, Boorjian SA, Buyyounouski MK, et al. NCCN Guidelines Insights: bladder cancer, version 5.2018. J Natl Compr Cancer Netw. 2018;16(9):1041–53.This 2018 update of the NCCN guidelines on bladder and upper tract cancer offers an overall review of the most recent studies and the present evidence-based recommendations for UTUC management.Google Scholar
- 38.Xylinas E, Colin P, Audenet F, Phe V, Cormier L, Cussenot O, et al. Intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinomas: predictors and impact on subsequent oncological outcomes from a national multicenter study. World J Urol. 2013;31(1):61–8.PubMedGoogle Scholar
- 39.O’Brien T, Ray E, Singh R, Coker B, Beard R, British Association of Urological Surgeons Section of O. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol. 2011;60(4):703–10.PubMedGoogle Scholar
- 40.Ito A, Shintaku I, Satoh M, Ioritani N, Aizawa M, Tochigi T, et al. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013;31(11):1422–7.PubMedGoogle Scholar
- 42.Lu DD, Boorjian SA, Raman JD. Intravesical chemotherapy use after radical nephroureterectomy: a national survey of urologic oncologists. Urol Oncol. 2017;35(3):113 e1–7.Google Scholar
- 44.•Leow JJ, Martin-Doyle W, Fay AP, Choueiri TK, Chang SL, Bellmunt J. A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma. Eur Urol. 2014;66(3):529–41.In this systematic review and meta-analysis, the authors demonstrated an overall survival and disease-free survival benefit for cisplatin-based adjuvant chemotherapy in UTUC. More trials are needed to confirm the utility of neoadjuvant systemic therapy.Google Scholar