Advertisement

The Changing Landscape of Upper Tract Urothelial Carcinoma Management

      Upper tract urothelial carcinoma (UTUC) is a rare malignancy of the urinary system and comprise roughly 5%-10% of all urothelial cancers.
      • Rouprêt M
      • Babjuk M
      • Compérat E
      • et al.
      European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2017 update.
      Despite the rarity of this disease which makes large scale trials difficult to conduct, there have been significant advances recently in both treatment options and molecular characterization of UTUC. These advances today would likely not have been possible without historical studies that drew early interest in this rare malignancy and stimulated interest. One of these studies by Hall et al on the 30-year experience of a single academic center, published in Urology in 1998, has been cited over 500 times since it has been published.

      Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract : a 30-year experience in 252 patients. 1944;4295:1-8.

      This retrospective study examined the outcomes of 252 patients with UTUC that were treated by either radical nephroureterectomy (RNU; 77%) or parenchymal sparing surgery (PSS; 17%) consisting of distal ureterectomy/reimplant, segmental ureterectomy, open excision, and endoscopic ablation. Over a median follow-up of 64 months, the authors found a recurrence rate of 27% at a median time of 12 months with poor prognoses for patients with stage III disease (41% at 5 years) and a grim median survival of 6 months with stage IV disease. The only predictors of disease recurrence on multivariate analysis were primary tumor stage and RNU vs PSS. Given that PSS was a negative prognostic factor, the authors further examined the differences between the 2 cohorts. Despite having fewer patients with grade 3 tumors (grade 1 and 2 tumors were similar) in the PSS cohort, their 5-year disease specific survival was significantly lower (23% vs 49%) compared to RNU. This difference was primarily due to the poor outcomes of patients with grade 3 ureteral tumors who underwent distal ureterectomy/reimplant, of which 4/5 (80%) died from recurrent UTUC.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Rouprêt M
        • Babjuk M
        • Compérat E
        • et al.
        European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2017 update.
        Eur Urol. 2018; 73: 111-122https://doi.org/10.1016/j.eururo.2017.07.036
      1. Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract : a 30-year experience in 252 patients. 1944;4295:1-8.

        • Margulis V
        • Shariat SF
        • Matin SF
        • et al.
        Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration.
        Cancer. 2009; 115: 1224-1233https://doi.org/10.1002/cncr.24135
        • Bagrodia A
        • Kuehhas FE
        • Gayed BA
        • et al.
        Comparative analysis of oncologic outcomes of partial ureterectomy vs radical nephroureterectomy in upper tract urothelial carcinoma.
        Urology. 2013; 81: 972-978https://doi.org/10.1016/j.urology.2012.12.059
        • Xylinas E
        • Rink M
        • Margulis V
        • et al.
        Impact of renal function on eligibility for chemotherapy and survival in patients who have undergone radical nephro-ureterectomy.
        BJU Int. 2013; 112: 453-461https://doi.org/10.1111/j.1464-410X.2012.11649.x
        • Kaag MG
        • O'Malley RL
        • O'Malley P
        • et al.
        Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy.
        Eur Urol. 2010; 58: 581-587https://doi.org/10.1016/j.eururo.2010.06.029
        • Denker M
        • Boyle S
        • Anderson AH
        • et al.
        Chronic renal insufficiency cohort study (CRIC): overview and summary of selected findings.
        Clin J Am Soc Nephrol. 2015; https://doi.org/10.2215/CJN.04260415
        • Go AS
        • Chertow GM
        • Fan D
        • McCulloch CE
        • Hsu CY
        Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.
        N Engl J Med. 2004; 351: 1296-1305https://doi.org/10.1056/NEJMoa041031
        • Arancibia MF
        • Bolenz C
        • Michel MS
        • Keeley FX
        • Alken P
        The modern management of upper tract urothelial cancer: surgical treatment.
        BJU Int. 2007; 99: 978-981https://doi.org/10.1111/j.1464-410X.2007.06705.x
        • Tavora F
        • Fajardo DA
        • Lee TK
        • et al.
        Small endoscopic biopsies of the ureter and renal pelvis.
        Am J Surg Pathol. 2009; 33: 1540-1546https://doi.org/10.1097/PAS.0b013e3181aec42a
        • Hoffman-Censits J
        • Puligandla M
        • Trabulsi E
        • et al.
        LBA26 phase ii trial of neoadjuvant chemotherapy followed by extirpative surgery for patients with High Grade Upper Tract Urothelial Carcinoma (HG UTUC): results from ECOG-ACRIN 8141.
        J Urol. 2018; 199: e1166-e1167
        • Birtle AJ
        • Chester JD
        • Jones RJ
        • et al.
        Results of POUT: a phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC).
        J Clin Oncol. 2018; 36 (407-407)https://doi.org/10.1200/JCO.2018.36.6_suppl.407
        • Bellmunt J
        • De Wit R
        • Vaughn DJ
        • et al.
        Pembrolizumab as second-line therapy for advanced urothelial carcinoma.
        N Engl J Med. 2017; 376: 1015-1026https://doi.org/10.1056/NEJMoa1613683
        • Powles T
        • Durán I
        • van der Heijden MS
        • et al.
        Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial.
        Lancet. 2018; 391: 748-757https://doi.org/10.1016/S0140-6736(17)33297-X
        • Loriot Y
        • Necchi A
        • Park SH
        • et al.
        Erdafitinib in locally advanced or metastatic urothelial carcinoma.
        N Engl J Med. 2019; 381: 338-348https://doi.org/10.1056/nejmoa1817323
        • Petrylak D
        • de Wit R
        • Chi KN
        • et al.
        Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial.
        Lancet. 2017; 390: 2266-2277https://doi.org/10.1016/S0140-6736(17)32365-6
        • Bernardo C
        • Eriksson P
        • Marzouka N
        • Liedberg F
        • Sjödahl G
        • Höglund M
        Molecular pathology of the luminal class of urothelial tumors.
        J Pathol. 2019; https://doi.org/10.1002/path.5318
        • Knowles MA
        • Hurst CD
        Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity.
        Nat Rev Cancer. 2015; 15: 25-41https://doi.org/10.1038/nrc3817
        • Rouprêt M
        • Yates DR
        • Comperat E
        • Cussenot O
        Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (Lynch Syndrome) tumor spectrum.
        Eur Urol. 2008; 54: 1226-1236https://doi.org/10.1016/j.eururo.2008.08.008
        • Van Der Post RS
        • Kiemeney LA
        • Ligtenberg MJL
        • et al.
        Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers.
        J Med Genet. 2010; 47: 464-470https://doi.org/10.1136/jmg.2010.076992
        • Amira N
        • Rivet J
        • Soliman H
        • et al.
        Microsatellite instability in urothelial carcinoma of the upper urinary tract.
        J Urol. 2003; 170: 1151-1154https://doi.org/10.1097/01.ju.0000086551.22844.cd
        • Le DT
        • Durham JN
        • Smith KN
        • et al.
        Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
        Science (80-). 2017; 357: 409-413https://doi.org/10.1126/science.aan6733
        • Mateo J
        • Carreira S
        • Sandhu S
        • et al.
        DNA-repair defects and olaparib in metastatic prostate cancer.
        N Engl J Med. 2015; 373: 1697-1708https://doi.org/10.1056/NEJMoa1506859
        • Kleinmann N
        • Wirth G
        • Lin JS
        • et al.
        Thermo reversible hydrogel based delivery of mitomycin C (UGN-101) for treatment of upper tract urothelial carcinoma (UTUC).
        Bl Cancer. 2019; 5: 21-29https://doi.org/10.3233/BLC-180182
        • Kleinmann N
        • Matin S
        • Pierorazio P
        • et al.
        Lba-16 nephron-sparing management of low grade (Lg) utuc with ugn-101 (mitomycin gel) for instillation: the olympus trial experience.
        J Urol. 2019; 201: 2019https://doi.org/10.1097/01.ju.0000557508.23335.0a