Urothelial Tumors of the Upper

Urinary Tract and Ureter

CAMPBELL 11 TH EDITION
Agung Adhitya
Management of Positive Upper Tract Urinary Cytology
or Carcinoma in Situ

• urinary cytology (+) presence of urothelial

carcinoma. Most cases are from a bladder
• extravesical sites may be involved, upper
urinary tracts and the prostatic urethra in men
• Diagnosis is difficult limitations of radiographic
evaluation of upper tracts and the complexity
of upper tract endoscopy compared with the
bladder.
Management of Positive Upper Tract
Urinary Cytology or Carcinoma in Situ
 Management of Positive Upper Tract
Urinary Cytology or Carcinoma in Situ
• repeat the cytology
• upper tracts  CT urography
• bladder evaluation biopsies and tumor
resection if tumor is present
• Bladder (+)  intravesical therapy and/or tumor
resection  voided urinary cytologies
• Cytology (+)  selective cytologies each upper
urinary tract URS non contamination specimen
from bladder or urethra + prostatic urethra
specimen in men  resection of a representative
specimen of the prostatic urethra
 Carcinoma in Situ of the Upper Urinary Tracts
• diagnosis of CIS difficult  inability to
evaluate the urothelium of the upper tracts
with adequate tissue samples
• most cases persistent positive selective
cytology  absence of any ureteroscopic or
radiographic findings.
• Radical nephroureterectomy  unilateral
cytologic abnormality of upper tract to
eliminate presumed CIS.  not recommended
Carcinoma in Situ of the
Upper Urinary Tracts
 Carcinoma in Situ of the
Upper Urinary Tracts
• Upper tract cytology  same limitations in
specificity as does bladder cytology
• upper tract samples are of limited volume and
cell count compared with bladder
• Inflammation UTI or calculus false-
positive result
Carcinoma in Situ of the Upper Urinary
Tracts
• topical therapy  nephrostomy tube reliable
delivery system  initially with surgical
intervention absence of any histologic,
radiographic, or endoscopic finding  cytology
false-positive results and the high risk for bilateral
disease in the future
• segmental resection  not effective because
multifocality of the disease.
• Nephroureterectomy  indicated
radiographically or endoscopically  more than
just surface disease
Carcinoma in Situ of the
Upper Urinary Tracts
Carcinoma in Situ of the Upper Urinary
Tracts
• Re evaluation urinalysis
– Selective cytology
– cystoscopy every 3 months
– retrograde pyelography or ureteropyeloscopy every 6
months
– 1 to 2 years
• CIS of ureteral margins during radical cystectomy
 serial endoscopy and found that recurrences
were found at the site of the margin but also at
other sites
 Adjuvant Therapy.
After Organ-Sparing Therapy
• Extirpative surgery has a higher local recurrence to
minimize these risks  instillation of immunotherapeutic
or chemotherapeutic and brachytherapy of nephrostomy
tract
• Instillation therapy
– primary treatment for CIS and as adjuvant therapy after
endoscopic or organ sparing therapy
– antegrade through a nephrostomy tube and retrograde directly
into a ureteral catheter or with iatrogenically created
vesicoureteral reflux
– instillation  ureteral catheter placed suprapubically, but given
over tumor implantation  rarely used.
– low pressure and absence active infection to minimize sepsis
 Adjuvant Therapy.
After Organ-Sparing Therapy
• mytomicin and BCG  same agents used to treat
urothelial carcinoma of the bladder same with to
treat tumors of the upper urinary tract
• Gemcitabine  alternative to BCG with fewer
side effects
– insufficient clinical significance  rarity of the disease
– UTUC have a tumor biology different with bladder
tumor
– inadequate delivery system upper tract have an
adequate dwell time to enable a clinical response.
 Adjuvant Therapy.
After Organ-Sparing Therapy
• BCG via a nephrostomy for CIS 55 patients
57% 5-year recurrence-free survival
• adjuvant after endoscopic ablation had
inferior results
• mitomycin C  smaller numbers of patients
and variable  no definite conclusions
reached
• intrarenal perfusion of BCG 50% (5 of 10)
recurrence 50.9 months
 Adjuvant Therapy.
After Organ-Sparing Therapy
• Agent-specific complications  ramifications
of systemic absorption of the agent
• Brachytherapy to nephrostomy tract through
iridium wire  by Patel and coworkers (1996)
– No instances of tract recurrences in this series
– major complication  cutaneous fistula formation
requiring nephroureterectomy.
 Adjuvant Therapy.
After Organ-Sparing Therapy
 After Complete Excision
• stage T3, T4, & N+  radiation therapy after radical
surgery  decrease risk of local relapse
• 41 patients  decreased local recurrence but no effect
on distant relapse or survival
• 26 patients  46 Gy
• Tumor stage was T2, T3, and N+ in 42%, 58%, and 35% of cases
• 5-year survival was 49%,with 30% remaining disease free
• 252 patients
• T3 : overall 5-year survival rates with or without adjuvant  41%
and 28%
• T4 : survival 6 months with or without adjuvant  45% and 40%
• relapse occurred in 9%
 After Complete Excision
• adjuvant radiation  isolated local relapse
without distant metastases 10% (T3) and 4%
(T4)
• radical nephroureterectomy high rate of
local control.
• combined radiation chemotherapy 
advanced disease  evidence supporting this
is small and retrospective
 After Complete Excision
• Chemotherapy  many patients have baseline
chronic kidney disease  worsens after
nephroureterectomy  ineligible to receive full
dose cisplatinum
• 15 patients T2-T4
– MVAC (methotrexate, vinblastine, Adriamycin, and cisplatin)
– MEC (methotrexate, etoposide, and cisplatin)
– MVEC (methotrexate, vinblastine, epirubicin, and cisplatin)
– before nephroureterectomy  13% complete
responses and 40% partial responses
 After Complete Excision
• 27 patients T3  16 patient received platinum
based therapy after nephroureterectomy 
no significant difference in recurrence free
and disease specific survival 40 months
• lack of controlled trials that establish the
efficacy  neoadjuvant or adjuvant
chemotherapy in UTUC
 Treatment of Metastatic Disease
• chemotherapy in metastatic UTUC  decline in
renal function after nephroureterectomy 
compromise ability to administer effective
postoperative chemotherapy
• lymph node (+)  initial chemotherapy surgery
withheld until a complete radiographic response
• MVAC highest response  toxicity prohibits
optimal dosage and duration  complete
responses rare in the metastatic  overall
survival of 12 to 24 months
 Treatment of Metastatic Disease
• Carboplatin is frequently substituted for cisplatin
 limitations of renal function or concerns over
toxicity  results remain inferior
• randomized phase III study
• paclitaxel, cisplatin, and gemcitabine (PCG) VS.
gemcitabine and cisplatin (GC)
• metastatic and locally advanced urothelial cancer
• follow-up of 4.6 years
• overall survival 15.8 months vs. 12.7 months
• overall response rate 55.5% vs. 43.6%
• The inhibitor of MET and VEGF pathways, in
patients in whom previous chemotherapy has
failed.
• phase I trials in metastatic urothelial
carcinoma  Targeting inhibitory surface
receptor PD-1, activation of which by PD-L1
ligand confers inhibition of T-cell proliferation
and cytokine production
• ongoing phase II and III trials
Treatment of Metastatic Disease
EAU, 2016
 summary
• UTUC like bladder cancer, is chemosensitive
chemotherapy are toxic and lack sustained
response.
• population  chronic kidney disease 
worsens after nephroureterectomy
• novel targeted therapies and experimentation
with new chemotherapeutic  optimize
treatment of metastatic UTUC