Avoid common mistakes on your manuscript.
Upper urinary tract urothelial carcinoma, UTUC, is a rare potentially lethal malignancy with increasing incidence. Since 2017, the EAU guidelines recommend radical nephroureterectomy (NU) in organ-confined high-risk UTUC, and that kidney sparing treatment (KST) is considered in all low-risk cases [1]. The high risks associated with nephron loss, expanding options for KST and the corresponding disease specific survival (DSS) rates of KST being as good as after NU have urged this evolvement. However, KST requires life-long follow-up with ureterorenoscopies.
With expanding treatment options, it is crucial to identify patients having true high-risk disease. To aid treatment choices, the EAU guidelines group in 2015 suggested dividing UTUC into high- and low-risk UTUC. Data to support this was mainly based on retrospective studies, defining preoperative findings associated with high and low risk of disease progression. The guidelines have evolved over the years. Some prognostic factors are considered robust (grade and stage) whereas others (tumour size and multifocality) are debated. The newly updated AUA guidelines [2] have taken this into account and primarily divide UTUC into low- and high-risk disease based on tumour grade in biopsy specimens, whereas other findings as radiographic signs of invasiveness and multifocality are secondary and considered unfavorable if present. The risk classification is relevant. When low-risk patients are treated organ sparingly the long-term results are as least as good as after NU. High-grade UTUC has a poor prognosis (five-year DSS of < 50%) whereas patients with low-risk UTUC have five-year DSS in the range 80–90% irrespective of treatment modality [3, 4]. Accordingly, a diagnostic work-up to distinguish low-risk from high-risk UTUC is mandatory.
According to the EAU guidelines the diagnostic work-up should include cystoscopy to rule out urinary bladder tumour, voided urinary or selective urine cytology and imaging, and if these investigations are not sufficient for accurate diagnosis or risk classification a ureterorenoscopy with diagnostic sample collection should be performed. As for diagnostic imaging, the method of choice of today is multiphase CT-scan (3 or 4 phases). Voided urinary cytology as well as selective urinary cytology has poor sensitivity and URS with focal samples (biopsies and cytology) is often needed, not only for diagnosis but for accurate risk classification.
A problem though is that despite proper diagnostics and radical treatment of organ confined disease, approximately 50% of the patients in the high-risk group will recur and even die from the disease. Also, patients in the low-risk group will recur and die from UTUC, but to a much lesser extent. Thus, current diagnostic methods have limitations, especially for prognostication. Identifying which patients who is at risk for recurrence and progression is crucial for targeted treatment choices and follow-up programs. Hence, there is an urgent need for diagnostic and prognostic markers to identify true high-risk tumours.
To explore difficulties in diagnostics and prognostication in UTUC, we invited experts in Europe and USA to participate in the “Consultation on UTUC 2022”, where strengths and limitations of current diagnostic tools and possible new prognostic markers were discussed.
Numerous markers have been investigated. Gene mutations in tumour tissue [5, 6] and in liquid biopsies [7], analysis of pathway proteins, endosomes and cytochines in urine, focal barbotages and plasma [8, 9]and volumetric 3D-microscopy imaging of tumour tissue [10] are all subject to research, although most of them have primarily been tested for urothelial carcinoma of the bladder (UCB). However, such data cannot be immediately extrapolated to UTUC, since UTUC in several ways differs from UCB, and there is a need to further evaluating such markers specifically in UTUC.
The experts were assigned different topics within the field. They prepared presentations according to the standards for a scoping review by scanning the literature using Pubmed, Embase, Web of Science and their own experience within the research field. The meeting took place at the Nobel Forum in Stockholm, September 2022 and extended over two days where the first day was a closed meeting for the experts, where all presentations were presented, discussed, challenged, and adjusted accordingly. The second day was an open meeting where the adjusted presentations were presented and discussed to an audience with participants from all over Europe. The meeting has resulted in two review papers [11, 12] covering diagnosis and follow-up of UTUC as we know of today and possible additional diagnostic and prognostic markers in the future.
Data availability
Not applicable.
References
Rouprêt M, Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM et al (2020) (2020) European Association of urology guidelines on upper tract urothelial carcinoma: 2020 update. Eur Urol. https://doi.org/10.1016/j.eururo.2020.05.042
Coleman JA, Clark PE, Bixler BR, Buckley DI, Chang SS, Chou R, Hoffman-Censits J, Kulkarni GS, Matin SF, Pierorazio PM, Potretzke AM, Psutka SP, Raman JD, Smith AB, Smith L (2023) Diagnosis and management of non-metastatic upper tract urothelial carcinoma: AUA/SUO guideline. J Urol 209(6):1071–1081. https://doi.org/10.1097/JU.0000000000003480. (Epub 2023 Apr 25 PMID: 37096584)
Grasso M, Fishman AI, Cohen J, Alexander B (2012) Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma: a 15-year comprehensive review of 160 consecutive patients. BJU Int 110(11):1618–1626. https://doi.org/10.1111/j.1464-410X.2012.11066.x. (Epub 2012 Mar 28 PMID: 22458598)
Seisen T, Peyronnet B, Dominguez-Escrig JL, Bruins HM, Yuan CY, Babjuk M, Böhle A, Burger M, Compérat EM, Cowan NC, Kaasinen E, Palou J, van Rhijn BW, Sylvester RJ, Zigeuner R, Shariat SF, Rouprêt M (2016) 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 70(6):1052–1068. https://doi.org/10.1016/j.eururo.2016.07.014. (Epub 2016 Jul 28 PMID: 27477528)
Sfakianos JP, Cha EK, Iyer G, Scott SN, Zabor EC, Shah RH, Ren Q, Bagrodia A, Kim PH, Hakimi AA, Ostrovnaya I, Ramirez R, Hanrahan AJ, Desai NB, Sun A, Pinciroli P, Rosenberg JE, Dalbagni G, Schultz N, Bajorin DF, Reuter VE, Berger MF, Bochner BH, Al-Ahmadie HA, Solit DB, Coleman JA. Genomic Characterization of Upper Tract Urothelial Carcinoma. Eur Urol. 2015 Dec;68(6):970–7. doi: https://doi.org/10.1016/j.eururo.2015.07.039. Epub 2015 Aug 14. PMID: 26278805; PMCID: PMC4675454.
Grahn A, Eisfeldt J, Malm C, Foroughi Asl H, Jaremko G, Tham E, Brehmer M (2022) Genomic profile - a possible diagnostic and prognostic marker in upper tract urothelial carcinoma. BJU Int 130(1):92–101. https://doi.org/10.1111/bju.15566. (Epub 2021 Aug 29 PMID: 34375486)
Fujii Y, Sato Y, Suzuki H, Kakiuchi N, Yoshizato T, Lenis AT, Maekawa S, Yokoyama A, Takeuchi Y, Inoue Y, Ochi Y, Shiozawa Y, Aoki K, Yoshida K, Kataoka K, Nakagawa MM, Nannya Y, Makishima H, Miyakawa J, Kawai T, Morikawa T, Shiraishi Y, Chiba K, Tanaka H, Nagae G, Sanada M, Sugihara E, Sato TA, Nakagawa T, Fukayama M, Ushiku T, Aburatani H, Miyano S, Coleman JA, Homma Y, Solit DB, Kume H, Ogawa S (2021) Molecular classification and diagnostics of upper urinary tract urothelial carcinoma. Cancer Cell 39(6):793-809.e8. https://doi.org/10.1016/j.ccell.2021.05.008.PMID:34129823;PMCID:PMC9110171
Vollmer T, Schlickeiser S, Amini L, Schulenberg S, Wendering DJ, Banday V, Jurisch A, Noster R, Kunkel D, Brindle NR, Savidis I, Akyüz L, Hecht J, Stervbo U, Roch T, Babel N, Reinke P, Winqvist O, Sherif A, Volk HD, Schmueck-Henneresse M. The intratumoral CXCR3 chemokine system is predictive of chemotherapy response in human bladder cancer. Sci Transl Med. 2021 Jan 13;13(576):eabb3735. doi: https://doi.org/10.1126/scitranslmed.abb3735. PMID: 33441425.
Hiltbrunner S, Mints M, Eldh M, Rosenblatt R, Holmström B, Alamdari F, Johansson M, Veerman RE, Winqvist O, Sherif A, Gabrielsson S (2020) Urinary exosomes from bladder cancer patients show a residual cancer phenotype despite complete pathological downstaging. Sci Rep 10(1):5960. https://doi.org/10.1038/s41598-020-62753-x.PMID:32249794;PMCID:PMC7136268
Tanaka N, Kaczynska D, Kanatani S, Sahlgren C, Mitura P, Stepulak A, Miyakawa A, Wiklund P, Uhlén P. Mapping of the three-dimensional lymphatic microvasculature in bladder tumours using light-sheet microscopy. Br J Cancer. 2018 Apr;118(7):995–999. doi: https://doi.org/10.1038/s41416-018-0016-y. Epub 2018 Mar 8. PMID: 29515257; PMCID: PMC5931093.
Sydén F, Baard J, Bultitude M et al (2023) Consultation on UTUC II Stockholm 2022: diagnostics, prognostication, and follow-up—where are we today? World J Urol. https://doi.org/10.1007/s00345-023-04530-9
Grahn A, Coleman JA, Eriksson Y et al (2023) Consultation on UTUC II Stockholm 2022: diagnostic and prognostic methods—What’s around the corner? World J Urol. https://doi.org/10.1007/s00345-023-04597-4
Calleris G, Rouprêt M, Seisen T et al (2023) Design and rationale of a single-arm phase II study of neoadjuvant Durvalumab and Gemcitabine associated with Cisplatin or Carboplatin for upper urinary tract urothelial cancer: the iNDUCT trial (NCT04617756). World J Urol. https://doi.org/10.1007/s00345-023-04596-5
Mu N, Jylhä C, Axelsson T et al (2023) Patient-specific targeted analysis of circulating tumour DNA in plasma is feasible and may be a potential biomarker in UTUC. World J Urol. https://doi.org/10.1007/s00345-023-04583-w
Figaroa, O.J.A., Hendriks, N., Kamphuis, G.M. et al. Positioning the role of urine cytology within the diagnostic pathway for UTUC: supportive but inconclusive. World J Urol (2023). https://doi.org/10.1007/s00345-023-04689-1
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Brehmer, M., Osther, P. Consultation on UTUC Stockholm 2022. World J Urol 41, 3393–3394 (2023). https://doi.org/10.1007/s00345-023-04693-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00345-023-04693-5