Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas Dept. of Urology Centro Hospitalar do Porto March 11th, 2017

UTUC Epidemiology Location Invasive 2/3 5-10% 60% 1/3 90-95% 15-25% Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

UTUC Epidemiology Synchronicity Recurrence 2-6% 17% 2% 22-47% 2% Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

UTUC Radical nephroureterectomy with bladder cuff excision (+/- lymph node dissection) Gold standard Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Gold standard Radical nephroureterectomy with bladder cuff excision (+/- lymph node dissection) But… Perioperative complications: 26% 26% Clavien ≥ III Mortality rate at 90 days: 4.4% T1: 2.4% G1/G2: 2.6% 45.1% for renal insufficiency Raman et al. 2014 Urol Oncol Jeldres et al. 2010 Urology Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

CKD and RNU eGFR (mL/min/1.73m2) n < 60, pre < 60, post 336 52% 78% - 388 51% 81% 20% 45% 414 76% 32% 66% Lane et al. 2010 Cancer Kaag et al. 2010 Eur Urol Raman et al. 2014 Urol Oncol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

ESRD survival Pak et al. 2009 J Endourol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Cost analysis Pak et al. 2009 J Endourol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Conservative tx Imperative Elective Solitary functional kidney Bilateral tumour Preexisting CKD Normal contralateral kidney Patient selection Accurate staging Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Radical vs. conservative tx No RCT’s Only retrospective case series and non-randomised comparative studies Selection bias Variation in indication Short or intermediate-term follow-up Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Conservative tx Segmental ureterectomy Partial nephrectomy / Pyelectomy Percutaneous resection Ureteroscopic ablation Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Risk stratification – elective Low-risk High-risk Low-grade ureteroscopic biopsy Low-grade cytology Tumour size < 1 cm No invasive features on cross-sectional imaging Unifocal disease Close follow-up possible and acceptable to patient High-grade ureteroscopic biopsy High-grade cytology Tumour size > 1 cm Invasive features on cross-sectional imaging Hydronephrosis Multifocal disease Failed endoscopic treatment of “low-risk tumour” Previous bladder tumour/cystectomy Smoking Rouprêt et al. 2014 Eur Urol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Staging Endoscopic Treatment of Upper Tract Urothelial Tumours Uro-CT Cytology Biopsy Treatment decision Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Uro-CT Filling defect Wall thickening Hydronephrosis Parenchymal invasion Bard et al. 2017 Nat Rev Urol van der Molen et al. 2008 Eur Radiol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Before instrumentation Urinary cytology Selective, in situ Before instrumentation Suboptimal Messer et al. 2011 BJU Int Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Ureteroscopic biopsy Limitations Inadequate tissue volume Artefacts (crushing) Non-representative sampling Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Ureteroscopic biopsy Rojas et al. 2013 Urol Oncol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Ureteroscopic biopsy Suboptimal PPV 92% 60% Clements et al. 2012 J Endourol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Ureteroscopic biopsy Routine diagnostic ureteroscopy Decrease RNU from 89% to 69% (NNT = 5) Decrease misdiagnoses from 15.5% to 2.1% (NNT = 7.5) Tsivian et al. 2014 J Endourol Technical success ≈ 95% with flexible ureteroscopy Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Prediction models PPV = 89% when all 3 present Brien et al. 2010 J Urol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Prediction models AUC = 71% Favaretto et al. 2011 BJU Int Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Flowchart Bard et al. 2017 Nat Rev Urol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Endoscopic tx URS ablation n (% imperative) 736 (32) Follow-up (median) in mo 14 – 73 (37) Upper tract recurrence 53% Bladder recurrence 34% Overall survival 72% Disease-specific survival 91% Nephroureterectomy rate 19% Progression 15% Failed endo management 24% Complication rate 14% # Similar CSS after endoscopic treatment of low-grade non-invasive tumors, but increased risk of local recurrence Seisen et al. 2016 Eur Urol # 11% stricture Cutress et al. 2012 BJU Int Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Digital flexible ureteroscopy Improving imaging Digital flexible ureteroscopy Bard et al. 2017 Nat Rev Urol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

NBI 5 additional tumours (14.2%) + extended limits of 3 tumours (8.5%) detected Traxer et al. 2011 J Endourol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

SPIES No studies in UTUC Baard et al. 2017 Nat Rev Urol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

PDD with oral 5-ALA 26 biopsies 11 visible under both white and blue light: 100% malignant 10 visible only under blue light – 70% malignant 5 random biopsies of normal mucosa – 100% benign Ahmad et al. 2012 BJU Int Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

OCT 26 patients In 83% staging was in accordance with final histopathology (RNU or SU) For tumour invasion: sensitivity of 100% and specificity of 92% Bus et al. 2016 J Urol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

CLE Ongoing studies for UTUC Bui et al. 2015 J Endourol Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas

Take-home message In imperative cases conservative management should be offered to patients. Patients with low-risk disease should be offered (as a default) endoscopic management with laser ablation as an option. To date, this statement relies mainly on low level evidence; further clinical research is absolutely mandatory. Meticulous and stringent follow-up is a key component of low-risk disease, with the potential for numerous repeat scans or endoscopic procedures. Patients with high-risk disease should by default proceed to early RNU. Endoscopic Treatment of Upper Tract Urothelial Tumours Vítor Cavadas