Therapie des high-risk Urothelkarzinoms des oberen Harntraktes

Zusammenfassung

Das Urothelkarzinom des oberen Harntrakts („upper tract urothelial carcinoma“, UTUC) stellt eine seltene Tumorerkrankung dar, die häufig erst in fortgeschrittenen Stadien diagnostiziert wird. Die Diagnostik basiert auf einer CT-Urografie, Spülzytologie aus dem oberen Harntrakt und einer Ureterorenoskopie (URS). Die Risikostratifizierung in eine Low- und High-Risk-UTUC dient als Grundlage für die Therapieentscheidung. Beim High-Risk-UTUC stellt die radikale Nephroureterektomie (RNU) mit Blasenmanschettenresektion den operativen Standard dar, wobei in selektionierten Fällen auch nierenerhaltene Verfahren erwogen werden können. Da die RNU einen signifikanten Rückgang der Nierenfunktion mit sich bringt und erste prospektive Daten eine gute radiologische und pathologische Remissionsrate zeigen, wird die neoadjuvante Chemotherapie beim UTUC zunehmend diskutiert. Der Behandlungsstandard hingegen für Tumoren im pT2–pT4-Stadium oder bei einem positiven Lymphknotenstatus (pN+) ist die adjuvante platinbasierte Kombinationschemotherapie, sofern diese nicht bereits als neoadjuvante Therapie erfolgt ist. Die adjuvante Immuntherapie mit Nivolumab zeigte in der UTUC-Kohorte im Vergleich zum Harnblasenkarzinom keinen signifikanten Therapievorteil und sollte nur Patienten im Tumorstadium ≥pT3 und/oder pN+ (oder ≥ypT2 und/oder ypN+ nach neoadjuvanter Chemotherapie) angeboten werden, die für eine platinbasierte Kombinationschemotherapie ungeeignet sind oder diese ablehnen.

Abstract

Upper tract urothelial carcinoma (UTUC) is a rare malignancy that is frequently diagnosed at an advanced stage. The diagnostic methods include CT urography, cytology of the upper urinary tract, and ureterorenoscopy (URS). Treatment decisions are guided by risk stratification into low- and high-risk UTUC. In cases of high-risk UTUC, radical nephroureterectomy with bladder cuff excision is considered the surgical gold standard. However, organ-sparing procedures may also be considered in selected cases. Due to the significant reduction in kidney function following RNU and recent prospective data showing favourable radiological and pathological remission rates, the importance of neoadjuvant chemotherapy is being increasingly discussed. For tumours classified as pT2 to pT4 or those with positive lymph node involvement (pN+), adjuvant platinum-based combination chemotherapy is recommended, provided that neoadjuvant chemotherapy has not already been administered. Adjuvant immunotherapy with nivolumab demonstrated no significant therapeutic benefit in the UTUC cohort compared with its use for the treatment of bladder cancer. It should only be considered for patients with tumours ≥pT3 and/or pN+ (or≥ypT2 and/or ypN+ after neoadjuvant chemotherapy) who are either ineligible for or decline platinum-based combination chemotherapy.

Schlüsselwörter

Urothelkarzinom des oberen Harntrakts - high-risk UTUC - Nephroureterektomie - perioperative Systemtherapie

Keywords

Upper tract urothelial carcinoma - high-risk UTUC - nephroureterectomy - perioperative systemic therapy

• Literatur

• 1 Masson-Lecomte A. et al. AU Guidelines on Upper Urinary Tract Urothelial Cell Carcinoma. Edn. presented at the EAU Annual Congress Paris 2024. Arnhem, The Netherlands: EAU Guidelines Office; ISBN: 978-94-92671-23-3 https://uroweb.org/guidelines
• 2 Dickman KG, Fritsche H-M, Grollman AP. et al. Epidemiology and Risk Factors for Upper Urinary Urothelial Cancers. In: Shariat SF, Xylinas E. , Hrsg. Upper Tract Urothelial Carcinoma. New York, NY: Springer New York; 2015: 1-30
• 3 Lonati C, Moschini M, Simeone C. et al. Lynch syndrome in urological practice: diagnosis, therapeutic strategies, and screening for upper tract urothelial carcinoma. Curr Opin Urol 2022; 32: 40-47
• 4 Herout R, Baunacke M, Flegar L. et al. Upper tract urothelial carcinoma in Germany: epidemiological data and surgical treatment trends in a total population analysis from 2006 to 2019. World J Urol 2023; 41: 127-133
• 5 Doeveren T van, Mark M van der, Leeuwen PJ van. et al. Rising incidence rates and unaltered survival rates for primary upper urinary tract urothelial carcinoma: a Dutch population-based study from 1993 to 2017. BJU Int 2021; 128: 343-351
• 6 Baard J, Cormio L, Cavadas V. et al. Contemporary patterns of presentation, diagnostics and management of upper tract urothelial cancer in 101 centres: the Clinical Research Office of the Endourological Society Global upper tract urothelial carcinoma registry. Curr Opin Urol 2021; 31: 354-362
• 7 Janisch F, Shariat SF, Baltzer P. et al. Diagnostic performance of multidetector computed tomographic (MDCTU) in upper tract urothelial carcinoma (UTUC): a systematic review and meta-analysis. World J Urol 2020; 38: 1165-1175
• 8 Zhao Y, Deng F-M, Melamed J. et al. Diagnostic role of urine cytology and ureteroscopic biopsies in detection of high grade upper tract urothelial carcinoma. Am J Clin Exp Urol 2021; 9: 221-228
• 9 Foerster B, Shariat SF, Klein JT. et al. Biopsy techniques in the upper urinary tract for the diagnosis of urothelial carcinoma: systematic review. Urologe A 2019; 58: 14-21
• 10 Subiela JD, Territo A, Mercadé A. et al. Diagnostic accuracy of ureteroscopic biopsy in predicting stage and grade at final pathology in upper tract urothelial carcinoma: Systematic review and meta-analysis. Eur J Surg Oncol 2020; 46: 1989-1997
• 11 Klein JT, John A, Bohnert L. et al. Improving the Quality of Human Upper Urinary Tract Specimens by Cryobiopsy. Front Oncol 2022; 12: 810367
• 12 Bus MTJ, Bruin DM de, Faber DJ. et al. Optical diagnostics for upper urinary tract urothelial cancer: technology, thresholds, and clinical applications. J Endourol 2015; 29: 113-123
• 13 Kriegmair MC, Hein S, Schoeb DS. et al. Enhanced imaging in urological endoscopy. Urologe A 2021; 60: 8-18
• 14 Müller-Lisse M, Hocaoglu Y, Püls M. et al. Grundsätzliche Eignung der Katheter-gestützten optischen Kohärenztomographie (OCT) für die Darstellung der menschlichen oberen Harnwege in vivo. Rofo 2008; 180: VO_302_3
• 15 Peyronnet B, Seisen T, Dominguez-Escrig J-L. et al. Oncological Outcomes of Laparoscopic Nephroureterectomy Versus Open Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An European Association of Urology Guidelines Systematic Review. Eur Urol Focus 2019; 5: 205-223
• 16 Kondo T, Hashimoto Y, Kobayashi H. et al. Template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract: impact on patient survival. Int J Urol 2010; 17: 848-854
• 17 Peyrottes A, Califano G, Ouzaïd I. et al. Lymph Node Dissection During Radical Nephro-Ureterectomy for Upper Tract Urothelial Carcinoma: A Review. Front Surg 2022; 9: 852969
• 18 O’Brien T, Ray E, Singh R. et al. 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: 703-710
• 19 Yamamoto S, Sakamoto S, Imamura Y. et al. Intravesical irrigation might prevent bladder recurrence in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma. Int J Urol Off J Japanese Urol Assoc 2019; 26: 791-796
• 20 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: 581-587
• 21 Huang Z, Zhang X, Zhang X. et al. Segmental Ureterectomy is Acceptable for High-risk Ureteral Carcinoma Comparing to Radical Nephroureterectomy. J Investig Surg 2019; 32: 746-753
• 22 Kato T, Nakayama R, Haba T. et al. Oncological and renal outcomes of segmental ureterectomy vs. radical nephroureterectomy for upper tract urothelial carcinoma. Oncol Lett 2018; 16: 6861-6867
• 23 Powles T, Catto JWF, Galsky MD. et al. Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer. N Engl J Med 2024; 391: 1773-1786
• 24 Birtle A, Johnson M, Chester J. et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet (London, England) 2020; 395: 1268-1277
• 25 Birtle AJ, Jones R, Chester J. et al. Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial. J Clin Oncol 2024; 42: 1466-1471
• 26 Bajorin DF, Witjes JA, Gschwend JE. et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med 2021; 384: 2102-2114