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Upper urothelial tract cancer and its surgical management Mr Charles Carey Core Surgical Trainee Learning objectives • Recognise how upper urothelial tract cancers (UTUC) may present • Understand which investigations are best for this condition • Evaluate how surgery can be used for both the diagnosis and management of UTUC • Understand how these patients are followed up and the complications they may experience 10/9/2024 Introduction • Malignancy within the lining of the renal calices, pelvis, ureteric and/or ureteric orifice urothelium • Relativeley rare • May be split into renal pelvicalyceal and ureteric disease • Almost always a transitional cell carciona (TCC) • CT urogram is often the initial gold standard operation of choice diagnostic • Many patients will require a ureteroscopy +/- biopsy • Kidney sparing and Neph-U represent radical methods of treatment 10/9/2024 Epidemiology • Represents around 5 – 10% of urothelial cancers and 10% of renal tumours • Estimated incidence = 2 per 100,000 person-years. • Peak incidence occurs between ages 70 – 90 years oMean age at diagnosis = 73 and had been rising • 40 – 50% present with NMID(pT1 or below) • 50 – 60% present with muscle invasive or more advanced disease (>/=pT2) • 25% present with metastases 10/9/2024idelines on Urothelial Carcinomasof the UpperUrinary Tract(UTUCs), 2024 guidelineson UrothelialCarcinomas of theUpper Urinary Tract (UTUCs), 2024;, Epidemiology, clinical presentation,and evaluation ofupper-tracturothelialcarcinoma - PMC(nih.gov) Epidemiology • Around 17% of patients with upper tract disease will also have bladder cancer • Those with bladder cancer or CIS are also more likely to develop an upper tract TCC • Many will seed TCC from the bladder to the upper tract • Patients with upper tract TCCs that are longer are at higher risk of bladder cancer recurrence 10/9/2024 Up to date; Yamashita, Ryo &Watanabe,Reiko & Ito, Ichiro & Shinsaka,Hideo & Nakamura, Masafumi& Matsuzaki, Masato & Niwakawa, Masashi. (2017). Risk factorsfor intravesical recurrence after nephroureterectomy in patients with upper urinary tract urothelialcarcinoma.International urology and nephrology. 49. 10.1007/s11255-017-1510-5. Pathology • >90% of upper tract tumours are TCCs and almost all are urothelial cancers • Other renal pelvis tumours include squamous cell carcinomas and adenocarcinomas • Urothelial cancers are inherentlymultifocal o May occur due to a single cancer cell spreading through the urothelium o Independent tumours occurring at different locations within the urothelium • Spread may occur within the lumen or between epithelial cells • UTUC may occur throughout the renal pelvis and ureter • Theirmorphology is similar to bladder TCCs Up to date; Petros FG. Epidemiology, clinical presentation, and evaluation of upper-tract urothelial carcinoma. TranslAndrol Urol. 2020Aug;9(4):1794-1798. doi:10.21037/tau.2019.11.22. PMID:32944542; PMCID:PMC7475674. Pathology • 25% of tumours have some variation in their histology • Some for example have features of SCC despite mainly being TCC • SCCs may exist on their own out right – 1 – 7% • Other rare non-urothelial lesions o Adenocarcinoma, neuroendocrine, sarcoma • Benign lesions of the upper tract also exist o PUNLMP and inverted papilloma – urothelial o Fibroepithelial polyp – non-urothelial Up to date; Petros FG. Epidemiology, clinical presentation, and evaluation of upper-tract urothelial carcinoma. TranslAndrol Urol. 2020Aug;9(4):1794-1798. doi:10.21037/tau.2019.11.22. PMID:32944542; PMCID:PMC7475674. Some definitions • Synchronous tumours oMany primary carcinomas existing at the time of diagnosis • Metachronous tumours oTumours that develop one after the other 10/9/2Tziris N, Dokmetzioglou J, Giannoulis K, Kesisoglou I, Sapalidis K, Kotidis E, Gambros O. Synchronous and metachronous adenocarcinomas of the large intestine. Hippokratia. 2008 Jul;12(3):150-2. PMID: 18923668; PMCID: PMC2504401. Risk factors • Risk factors include: oMale gender – almost twice as common in men compared to women oSmoking – increases risk x 7.2 oPrevious bladder cancer oLynch syndrome – also increases the risk of colon cancer oAristocholic acid – found in Chinese herbal medication oChronic bacterial incection – increases the risk of SCC Sountoulides P, Pyrgidis N, Brookman-May S, Mykoniatis I, Karasavvidis T, Hatzichristou D. Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta- analysis. J Urol. 2021 Apr;205(4):956-966. doi: 10.1097/JU.0000000000001548. Epub2020 Dec 7. PMID: 33284711. Risk factors • Bladder TCC may have a higher chance of cancer seeding up into the ureter if a stent is in place o Metachronous tumour o Stenting may be considered duringTURBT if the resection occurs over a UO Sountoulides P, Pyrgidis N, Brookman-May S, Mykoniatis I, Karasavvidis T, Hatzichristou D. Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinomain Patients with Bladder Tumors? A Systematic ReviewandMeta-analysis. J Urol. 2021Apr;205(4):956-966. doi: 10.1097/JU.0000000000001548. Epub2020Dec 7. PMID: 33284711. Symptoms and presenting features • Haematuria • Flank pain • Weight loss, generally unwell, fatigue • Upper urothelial tract TCC is commonly asymptomatic oMay be found or suspected incidentally ▪ E.g. unilateral hydronephrosis seen on a CT KUB or USS, resulting in a CT-U 10/9/2024 Diagnosis • Incidence of UTUC has increased due to improved diagnostic methods • These have significantly helped diagnose early stage disease and CIS • The initial gold standarddiagnostic methodis now via a CT-urogram o Is usually diagnostic – 92% sensitive and 95% specific o Previously relied on IV pyelogram o Abnormalities that could represent cancer may be reported as masses or filling defects • Haematuria patients routinelyhave a CT urogram to detect these tumours • MRI may alsobe used for patients who cannot have contrast • Urinary cytology may alsobe taken but is commonly of limited use 10/9/2024 Diagnosis • The multifocality of UTUC means it needs a complete assessment – including flexi cystoscopy • Some scan results may be unclear • Many patients will therefore undergo a diagnostic ureteroscopy +/- biopsy • The URS allows for the direct visualisation of the ureter • Biopsy forceps if used safely, can sample tissue for histological analysis • Patients with confirmed disease will need a staging CT-TAP 10/9/2024 Ureteroscopy • Performed by inserting a rigid cystoscope and passing a wire into the UO • Make sure you set up your scope, including the white balance • Hold the penis up vertically and drop your hands as you enter the prostatic urethra • Pass the scope under/beside the wire into the UO and gently advance proximally • Identify the abnormality and proceed • Often performed with a rigid scope • Consider a flexible scope when lesions are invisible without camera deflection • Urine10/9/2024ampled for cytology during this procedure Ureteroscopy • Ureteroscopyis alsoa commonly used procedure duringtherapeutic procedures • Laser wires may be passed through the scope and be used to: o Dust and fragment stones o Ablate abnormal lesions. • Great care must be taken within the ureter as there is a high risk of perforation • Increases the risk of intravesicle recurrence • Beware of the fulcrum effect o With a long scope, small movements are exaggerated 10/9/2024 Treatment of upper tract urothelial carcinoma with ureteroscopy and thulium laser: a retrospective single center study - PMC (nih.gov) Family screening • Given the association between UTUC and hereditary cancers, take a thorough family Hx • Patients should ideally be screened using the Amsterdam II criteria if this is suspected 10/9/2024 Tumour grading • Most upper tract tumours have a high malignant potential • The 2022 WHO classification: o Papillary urothelial neoplasia of low malignant potential o Low-grade papillary UCs o High-grade papillaryUCs 10/9/2024 Tumour staging • T1 – invades the subepithelial connective tissue • T2 – invades the muscle layer. • T3 – invades intosurrounding fat • T4 – Invades into adjacent organs • N1 – invades intoa single LN <2cm • N2 – invades intoa single LN >2cm or many LNs • M1 – distant mets Hu, X.; Xue, Y.; Zhu, G. Clinical Characteristics and Current Status of Treatment for Recurrent Bladder Cancer after Surgeries on Upper Tract Urothelial Carcinoma. Diagnostics 2023, 13, 1004. https://doi.org/10.3390/diagnostics13051004 Tumour staging • Tumour staging is often difficult to assess in UTUC • Cases are therefore subdivided into low and high risk tumours • This helps decide between kidney sparing treatment and radical neph-U • This also helps decide on SACT and follow up EAU guidelines on Urothelial Carcinomas of the Upper Urinary Tract (UTUCs), 2024024 Low risk UTUC • All cases should be offered kidney sparing surgery • May involve endoscopic methods – e.g. laser ablation • May involve segmental resection of the ureter + anastomosis oBest for low risk distal tumours oHigh failure rates in the proximal 2/3s of the ureter oTotal ureterectomy + ileal-ureter anastomosis • Pe10/9/2024s methods exist for low risk renal pelvis tumours Nephroureterectomy (Neph-U) • Standard method for radical treatment of UTUC • Method has been around for >100 years in various forms In various forms • High rates of recurrence mean that the whole ureter should be removed • Open, laparoscopic and robotic assisted approaches exist • Usually characterised in 2 parts: o Radical nephrectomy o Distal ureterectomy 10/9/2024 Nephroureterectomy (Neph-U) • Nephrectomy may be performed open, lap or robotically • Open surgery o Advantages In various forms Approach to open RN can be: ▪ No special equipment •Flank or anterior ▪ Fallback procedure for minimally invasive cases • Retroperitoneal, ▪ Shorter operating times transperitoneal or thoraco- o Disavantages abdominal ▪ More post-op pain and higher risk of blood loss ▪ Longer hospital stays 10/9/2024car Nephroureterectomy (Neph-U) • Laparoscopic and robotic cases are performed with flank incisions • The renal artery(ies) need to be clipped before the renal veins oWhy? In various forms • Involves removing the kidney, para-nephric fat, perinephric fat and gerota's fascia • Key considerations. o Avoid urine spillage o Ensure the ureter is completely removed – including the cuff of the bladder o Hydronephrotic kidneys are easier to rupture. 10/9/2024 Nephroureterectomy (Neph-U) • The whole of the distal ureter + bladder cuff should be removed o Not leaving a bladder cuff has been associated with poorer cancer-specific and overall survival • Removing this section may be performed ia In various formsly invasive approaches • Open distal ureterectomy is the historical gold standard • Bladder cuff excision requires a cystoscopy and incision around the UO • This may be performed intra- or extravesically 10/9/2024rton GJ, Tan WP, Inman BA. The nephroureterectomy: a reviewof techniqueand current controversies. Transl Androl Urol 2020;9(6):3168- 3190. doi: 10.21037/tau.2019.12.07 Additional management options • Radical surgery may be accompanied by: o Neoadjuvant and/or adjuvant chemo o Template lymph node dissection In various forms o Intravesicle chemo o Immunotherapy o Radiotherapy 10/9/2024 Follow up • After radical neph-u o Low risk cancer ▪ Cystoscopy at 3 months – if negative performcystoscopy 9 months later and then yearly for 5 years. o High risk cancer In various forms ▪ Cystoscopy and urine cytology at 3 months ▪ If negative, perform cystoscopy and cytology every 3 months for 2 years, every 6 months for 5 years and yearly thereafter ▪ CT-urogram and thorax 6 monthly for 2 years and then yearly 10/9/2024 Follow up • After kidney sparing management o Low risk cancer ▪ Cystoscopy and CT-urogram at 3 and 6 months and then yearly for 5 years ▪ URS at 3 months In various forms o High risk tumours ▪ Cystoscopy, urinary cytology, CT urogram and thorax at 3 and 6 months and then yearly ▪ URS + concurrent urinary cytology in 3 and 6 months 10/9/2024 EAU guidelines on UrothelialCarcinomas of the Upper Urinary Tract (UTUCs), 2024Questions Thanks for coming! 10/9/2024