1. Oncology 7 Upper Tract TCC
James Dyer
Richard Robinson
Dan Burke

2. Introduction Epidemiology Risk Factors Pathology Diagnosis
Relevant outcome studies
Treatment
Update on bladder cuff resection strategy
Role of lymphadenectomy
UUT-TCC May 2014

3. Epidemiology
Bladder Cancer 90%
Urothelial carcinoma 4th and 14th commonest cancer diagnosis in UK amongst men and women respectively (ONS)
Incidence 1-2 per 100,000/year
Peak incidence 10 per 100,000/year in 8th decade
Mean age at presentation is 65
Increasing incidence
Munoz et al. J Urol. 2000
munoz JJ, ellison lm. upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J urol 2000 nov;164(5):
SEER database study over 23 years with >9000 patients
Ureteric Cancer 5-10%
UUT-TCC May 2014

4. Epidemiology (2)
1-4% risk of synchronous contralateral tumour at presentation
3-6% risk of metachronous contralateral tumour
30% multifocal
Median time to diagnosis is 48 days (27days for bladder)
UUT-TCC May 2014

5. Incidence renal pelvis:ureter = 2:1
margulis v, shariat sF, matin sF, et al. outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. cancer 2009 mar;115(6):
Variablity in reported stage at presentation
Munoz JJ, Ellison LM. Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol Nov;164(5):1523-5 
8-13% synchronous bladder TCC
33-60% muscle-invasive at diagnosis
Munoz JJ. J Urol. 2000 
UUT-TCC May 2014

6. Histology 95% TCC 2004 TNM WHO criteria 2004 PUNLMP Low High
UUT-TCC May 2014

7. Staging Discrepancy in staging between MIBC and UUTTCC
UUT-TCC May 2014

8. Risk factors As for bladder TCC HNPCC Smoking
Occupation aromatic amine exposure
HNPCC
Index of suspicion in those <60 with other HNPCC tumours
Colon
Endometrium
Stomach
UUT-TCC May 2014

9. Presentation US single centre series of 252 pts over 32 years
Presenting features
Haematuria 78%
Flank pain 18%
Dysuria 6%
UTI 5%
Prior TCC
Bladder 12%
Upper tract 2%
Hall M.C. et al. Urology (4):
hall mc, Womack s, sagalowsky aI, et al. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. urology 1998 oct;52(4):
UUT-TCC May 2014

10. Diagnosis MDCTU – 96% sensitive lesions 5-10mm
Pre-contrast
Nephrogenic
Excretory phase
Gadolinium MRI when CTU contraindicated
Cystoscopy +/- retrograde
Cytology – in situ, independent predictor of high stage >pT3 & N+
Retrospective single centre analysis n=469
Brien JC. J Urol Jul
Brien JC, Shariat SF, Herman MP, Ng CK, Scherr DS, Scoll B, Uzzo RG, Wille M, Eggener SE, Terrell JD, Lucas SM, Lotan Y, Boorjian SA, Raman JD. Preoperative hydronephrosis, ureteroscopic biopsy grade and urinary cytology can improve prediction of advanced upper tract urothelial carcinoma. J Urol Jul;184(1):69-73
UUT-TCC May 2014

11. Diagnostic ureteroscopy
Useful in diagnostic uncertainty
Sensitivity of MDCTU falls with smaller lesions
96% lesions 5-10mm
89% lesions < 5 mm
40% lesions < 3 mm
Not mandated in EAU guidelines
Concerns over effect on subsequent bladder recurrence and DFS unfounded
Retrospective multicentre study
n=208, 55 preoperative ureteroscopy with no significant difference in survival/recurrence
Ishikawa et al. J Urol. 2010
Ishikawa S, Abe T, Shinohara N, Harabayashi T, Sazawa A, Maruyama S, Kubota K, Matsuno Y, Osawa T, Shinno Y, Kumagai A, Togashi M, Matsuda H, Mori T, Nonomura K. Impact of diagnostic ureteroscopy on intravesical recurrence and survival in patients with urothelial carcinoma of the upper urinary tract. J Urol Sep;184(3):883-7
UUT-TCC May 2014

12. Endoscopy and biopsy Accuracy of simple inspection
Low grade 71% high grade 80%
El-Hakim Urology 2004; 63,
Grade on biopsy predicts surgical stage
75-90% accuracy
87% low grade on biopsy staged Ta,T1
67% high grade on biopsy staged T2-3
Keeley J Urol 1997; 157, 33-7
T1 on biopsy – rarely upgraded
Ta on biopsy – 45% upgraded
Guarnizo J Urol 2000; 163, 52-5
UUT-TCC May 2014

13. Instruments
What are these?
UUT-TCC May 2014

14. Treatment - Localised Disease
RNU gold standard
Emerging evidence regarding lap vs. open
Oncological principles of;
Avoid opening urinary tract to avoid seeding
Essential to excise ureteric orifice with bladder cuff
Role of neo-adjuvant chemotherapy unclear
POUT trial analysing adjuvant chemotherapy post surgery (GC)
UUT-TCC May 2014

15. Bladder cuff
Multicentre retrospective case notes analysis of both lap and open RNU
Xylinas et al Eur Urol. 2014
2681 patients across 24 centres comparing distal cuff strategy
Transvesical
Extravesical
Endoscopic
Xylinas E, Rink M, Cha EK, Clozel T, Lee RK, Fajkovic H, Comploj E, Novara G, Margulis V, Raman JD, Lotan Y, Kassouf W, Fritsche HM, Weizer A, Martinez-Salamanca JI, Matsumoto K, Zigeuner R, Pycha A, Scherr DS, Seitz C, Walton T, Trinh QD, Karakiewicz PI, Matin S, Montorsi F, Zerbib M, Shariat SF; Upper Tract Urothelial Carcinoma Collaboration. Impact of distal ureter management on oncologic outcomes following radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol Jan;65(1):210-7.
UUT-TCC May 2014

16. UUT-TCC May 2014

17. Intravesical recurrence
UUT-TCC May 2014

18. Lymph nodes Lymphadenectomy allows accurate staging
Roscigno et al 2009 J Urol
Retrospective analysis 1130 pts with pN0,pNx and pN+ disease
pT1 pNx vs. pN0 – 5-year survival no difference
pT2-4 pNx vs. pN0 – 5-year survival (58% vs. 70%)
Rosignco et al Eur Urol 2009
Number of nodes associated with lower recurrence but not CSM
Number of nodes in N0 disease
>8 nodes HR 0.49 and 0.42 for recurrence and survival respectively
Roscigno M et al. Impact of lymph node dissection on cancer specific survival in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. J Urol Jun;181(6):2482-9
Roscigno M et al. The extent of lymphadenectomy seems to be associated with better survival in patients with nonmetastatic upper-tract urothelial carcinoma: how many lymph nodes should be removed? Eur Urol Sep;56(3):512-8
UUT-TCC May 2014

19. Treatment - Localised disease
Conservative surgery
Ureteroscopy and LASER
PCN
Segmental resection
+/- adjuvant MMC/BCG
MMC 40mg in 40 mls given at 13mls/hr for 3 hours via ureteric catheter
Reserved for;
Small <1cm, low stage, low grade TCC when contralateral kidney is normal
Renal insufficiency
Solitary functioning kidney
Supported by a number of small single centre retrospective analyses
Traxer group, Paris - Ureteroscopy
n=35, all for solitary kidney/comorbidity.
Follow up 30 months
Median time to recurrence 10 months
cornu Jn, rouprêt m, carpentier x, et al. oncologic control obtained after exclusive flexible ureteroscopic management of upper urinary tract urothelial cell carcinoma. World J urol 2010 apr; 28(2):151-6.
UUT-TCC May 2014

20. Results - URS Series N Recurrence n (%) DSS, % F/U mo
Elliot Urology 96 44
17 (38)
86.5
3-132
Martinez-Pineiro J Urol 96 28
8 (29) 93
2-119
Tawfiek Urology 97
205
65 (31.7) ND
2-132
Keeley J Urol 97 38
8 (28)
100
3-116
Chen J Urol 00 23
15 (65)
8-103
Daneshmand Cancer 03 26
23 (88)
4-106
Suh J Urol 03 18
3 (37.5)
3-48
Johnson BJUint 05 35
24 (68)
3-84
Sowter J Endourol 07
26 (74)
5-115
NU – performed in ~ 16% of patients for recurrence and progression
Low grade – 76% tumour free / high grade – 40%
Tumours >1.5cm – 36% tumour free 50% recurrence (small 91% and 25% respectively)
Multifocal – 50% incomplete resection (19% with solitary lesions)
Location – local recurrence renal pelvic 33% ureteric 31%
UUT-TCC May 2014

21. Results – Ureteroscopic management
Recurrence
30-40%
G1 – 30%
G2 – 57%
G3 – 60%
Keeley J Urol 97
5y survival
G1 – 100%
G2 – 80%
G3 – 60%
Elliot Urology 96
20 patients were elective; 3 needed NU; none died
UUT-TCC May 2014

22. Segmental ureterectomy
Segmental resection with re-implantation or interposition
Results show feasibility for distal ureter
Jeldres et al J Urol 2010;183:1324–9
Segmental resections of more proximal ureter associated with high recurrence rate
Mazeman Eur Urol 1976; 2, 120-8
UUT-TCC May 2014

23. Percutaneous approach
large tumours (renal, upper ureteric)
Percutaneous access as per PCNL
Resectoscope down access sheath
Loop resection
Retrograde balloon occlusion of ureter
Nephrostomy tube
Adjuvant treatment
Second examination (easier if tract present)
Risk of tumour implantation
Large sheath to reduce pressures and protect tissue
Tract irradiation (Iridium wire)
Delay adjuvant tx for 2weeks
Tract seeding – rare; 2 cases
UUT-TCC May 2014

24. Results – Percutaneous
Series
N (Renal units)
Recurrence %
DSS %
F/U mo
Jarrett J Urol 95
34 (36) 33 87
9-111
Patel J Urol 96
26 (26) 23
92.3
1-100
Clark J Urol 99
17 (18) 83
1.7-75
Jabour 2000
54 (54) 38 84
11-168
Goel J Urol 03
22 (22) 55
69.2
24-132
Suh J Urol 03
19 (19) 88
89.5
3-58
Palou J Urol 04
34 (34)
44.2
94.1
3-131
Roupret E Urol 06
24 (24)
79.5
18-188
UUT-TCC May 2014

25. Outcome and Recurrence Studies
Raman et al Eur Urol 2010
No difference in recurrence between pelvic and ureteric TCC (HR 1.0)
Multicentre retrospective analysis of >1200 pts following RNU
5-year cancer specific survival 78%
Only nodal status, stage, grade predicted recurrence and poor survival
However, 38% pelvic had pT2 disease and 22% of ureteric had pT2 disease
Contradicts previous theory that thin adventitia and rich blood supply contributed to greater muscle invasion and poor outcome in ureteric TCC
raman Jd, ng cK, scherr ds, et al. Impact of tumor location on Prognosis for Patients with upper tract urothelial carcinoma managed by radical nephroureterectomy. eur urol 2010 Jun;57(6):
UUT-TCC May 2014

26. Outcome and Recurrence Studies
Cha et al Eur Urol 2012
Multicentre (23 unit) study of 2244 patients with lap or open RNU over 20 year period with 44 median month FU
Used AJCC staging system
No prior MIBC or chemotherapy
22.3% recurrence
18.6 Cancer mortality
Data used to develop nomograms for DFR and CSS
Bladder recurrence not coded
Cha EK, Shariat SF, Kormaksson M, Novara G, Chromecki TF, Scherr DS, Lotan Y, Raman JD, Kassouf W, Zigeuner R, Remzi M, Bensalah K, Weizer A, Kikuchi E, Bolenz C, Roscigno M, Koppie TM, Ng CK, Fritsche HM, Matsumoto K, Walton TJ, Ehdaie B, Tritschler S, Fajkovic H, Martínez-Salamanca JI, Pycha A, Langner C, Ficarra V, Patard JJ, Montorsi F, Wood CG, Karakiewicz PI, Margulis V. Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol Apr;61(4):818-25
UUT-TCC May 2014

27. UUT-TCC May 2014

28. Therefore; LVI Sessile architecture CIS
Included on pathology report but tumour stage is the most important independent variable
UUT-TCC May 2014

29. Bladder recurrence Hall et al Urology 1998
Single centre series (n=252)
RNU and conservative tx
Heterogenous group of procedures/techniques
27% recurrence over median FU of 64 months
50% bladder equating to 13.5%
hall mc, Womack s, sagalowsky aI, et al. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. urology 1998 oct;52(4):
13.5 % over 30 year period – lower than other series
UUT-TCC May 2014

30. Bladder recurrence Retrospective review of 301 patients with RNU.
Comparison of distal ureteric excision
Intravesical
Extravesical
Transurethral
Median FU 33 months
bladder recurrence – 21.9%
No difference in recurrence rates with technique
Oddities!
More ureteric tumours than renal pelvic tumour
More women than men
azémar md, et al. bladder recurrence after surgery for upper urinary tract urothelial cell carcinoma: frequency, risk factors, and surveillance. urol oncol mar-apr;29(2):130-6.
UUT-TCC May 2014

31. Follow up – RNU EAU guidelines 2012
Metacronous tumour
Cystoscopy and cytology 3 months then yearly
Local recurrence
CTU annually (6 monthly for 2 years if invasive disease)
Distant metastasis
CTU
UUT-TCC May 2014

32. Follow up – conservative treatment
MDCT and cytology – 3 months, 6 months then yearly
Cystoscopy, ureteroscopy and cytology – 3 months, 6 monthly for 2 years then annually
UUT-TCC May 2014

33. Cases 1
70 year old smoker
Isolated episode of painless visible haematuria
How to proceed?
2 week wait referral – dedicated haematuria clinic
Flexible cystoscopy
MSU
Renal function tests
CT urogram
UUT-TCC May 2014

34. Case 3 75 Yr male. pT1 TCC upper ureter. Smoker CKD stage 2 Diabetic
Monday morning.
Patient admitted for lap nephroureterectomy.
Discuss procedure and consent.
UUT-TCC May 2014

35. Consent Lap. Nephroureterectomy
Discuss:
operative procedure (including discussion of management of distal ureter).
peri-operative management.
complications
follow up (including cystoscopy surveillance)
alternatives to treatment.
Complications
Common (greater than 1 in 10)
  Shoulder tip pain.
  Abdominal bloating.
  Recurrence of disease elsewhere in the urinary tract.
Occasional (between 1 in 10 and 1 in 50)
  Bleeding, infection, pain or hernia of the incision needing further surgery.
  Need for additional treatment for cancer after surgery.
Rare (less than 1 in 50)
  Recognised (or unrecognised) entry into the pleural cavity and possible chest drain insertion.
  Recognised (or unrecognised) injury to organs/blood vessels needing conversion to open surgery (or deferred open surgery).
  Anaesthetic or cardiovascular problems possibly requiring intensive care admission (including chest infection, pulmonary embolus, stroke, deep vein thrombosis, heart attack and death).
  Renal failure (temporary or permanent) requiring dialysis.
  The pathology in the kidney may subsequently be shown not to be cancer.
  Persistent urine leakage from the bladder needing prolonged catheterisation or further surgery.
Hospital-acquired infection
  Colonisation with MRSA (0.9% - 1 in 110).
  MRSA bloodstream infection (0.02% - 1 in 5000).
  Clostridium difficile bowel infection (0.01% - 1 in 10,000).
UUT-TCC May 2014

36. Case 4 - introduction 67 Yr female. Smoker. CKD stage 3a.
Previous recurrent multifocal G2pTa TCC bladder.
Course of mitomycin 3 years ago (no recurrence since).
Visible haematuria 6 weeks ago.
What would you do?
UUT-TCC May 2014

37. Case 4 – initial evaluation
History - 2 episodes of visible haematuria 6 weeks ago (none since).
Examination - normal
MSU – no evidence of infection.
Flexible cystoscopy – normal.
CTU – poor contrast filling of distal ureters, but no obvious abnormality.
What next?
UUT-TCC May 2014

38. Case 4 – first URS Bilateral ureteroscopy.
Small papillary tumour distal 1/3 left ureter.
Removed with basket and LASER to base of tumour.
No other abnormalities.
Low grade TCC
Path report – G2pTa
What next?
UUT-TCC May 2014

39. Case 4 – follow up Follow up URS in 3 months. Normal bladder.
No evidence of upper tract tumour.
Lost to follow up, living in Costa Brava for 3 years.
Represents again with visible haematuria.
What do you do?
UUT-TCC May 2014

40. Case 4 – re-evaluation
History – intermittent haematuria for 12 months.
Examination normal.
Flexi cystoscopy:
5 small papillary tumours in bladder.
? tumour protruding from left U.O.
What next?
UUT-TCC May 2014

41. CT 2 days prior to ureteroscopy. What does it show?
Bilateral URS – large tumour in right renal pelvis – biopsy taken. Multiple small papillary tumours left distal 4 cm ureter – biopsy and LASER.
CT 2 days prior to ureteroscopy. What does it show?
High grade TCC
Path report - right renal pelvis G3pT1
- left lower ureter G2pTa
- bladder G2 pTa
UUT-TCC May 2014

42. Case 4 – definitive managment
Patient returns to clinic to discuss results and treatment options:
Summary of case
67 Yrs, female, CKD stage 3a and smoker.
CT thorax requested at time of URS reported as clear.
CTU – renal pelvis TCC right – no other disease visible.
Recurrent G2 pTa bladder
Recurrent G2 pTa left distal ureter
New large G3 pT1 right renal pelvis
Treatment options are:
Right lap. NU, endoscopic management of bladder and distal ureter.
Right lap. NU, endoscopic management of the bladder and left distal ureterectomy and re-implantation of ureter.
Bilateral NU and radical cystectomy with implementation of dialysis.
UUT-TCC May 2014