Ureteric tumor and

it’s management
• Upper urinary tract carcinomas (UTUCs- Renal pelvis & ureter) make
up only 5% to 10% of urothelial tumors.

• UTUC – peak incidence-70-90 year age. M>F

• Approximately two-thirds of patients who present with UTUCs have

invasive disease at diagnosis
 Arterial Venous Lymphatic

Upper Ureter Main renal arteries Renal & gonadal vein Left- Para-aortic
(Medially) Right- Paracaval & IAC

Mid Ureter Common iliac Renal & gonadal vein Common iliac
(Posteriorly)

Low Superior vesical Common & internal iliac Common, external &
(Laterally) vein internal iliac
• Risk factors:-

Familial/hereditary.

• Tobacco relative risk -2.5 to 7.

• occupational exposure to carcinogenic aromatic amines.

• Balkan nephropathy - dietary exposure to aristocholic acid

• analgesic abuse.
• Lynch syndrome are found in 9% of patients with UTUC

Suspicion of hereditary UTUC

• Age <60 years

• Personal history of HNPCC-spectrum cancer or

• First-degree relative <50 years with HNPCC-spectrum cancer

• 90% of cancers of the renal pelvis and ureter are UC.

Distal- 70%
• Ureteric tumor Mid- 25%
Proximal- 5%
• Presentation:-
• Gross hematuria - 75% to 95%. Vermiform clots
• Colicky pain
• HUN
 1. Imaging of upper tract collecting system- CECT (? MRI )

2. Cystoscopy- To r/o concomitant BC

3. Urine cytology

4. Ureteroscopy ( for biopsy and tumor mapping) or

Work up
percutaneous biopsy and/or selective washings

5. Nuclear medicine renal scan (optional)

6. Chest x-ray or CT
 • Urine cytology:- sensitivity
LG tumor-10-40%
Less sensitive for
HG tumor - ~70%
UTUC a/c/t BC Stage
assessment
is difficult

Ureteroscopic evaluation and biopsy

Recent studies May

showed a higher rate -Diagnostic undergrading
of intravesical uncertainty - correlation-
recurrence in patients -Conservative 80-90%
CECT-STD of care!
who underwent URS management
Marchioni et al., before RNU
2017; Yoo et al., 2017
• In a meta-analysis comparing URS vs. no URS prior to RNU, 8/12 studies found an increased risk for
intravesical recurrence if URS was performed before RNU

• According to the European guidelines, the stage assessment with the URS biopsy is notoriously difficult.

• Therefore, histological grade is often used for clinical decision making as it is strongly associated with
pathological stage.

• Thus a more accurate prediction of the tumor stage and stratification of cases would require a
combination of tumor grade, visual inspection of the tumor, radiographic studies (presence of
obstruction), and urinary cytology

• Sharma, V., et al. The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis. J Urol, 2021. 206: 558.
• AJCC TNM staging

• N1- Single lymph node ≤2 cm

• N2- Single lymph node >2 cm ; or

multiple lymph nodes.
Important for decision making and the
selection of RNU or kidney-sparing
approach

.Micropapillary
.Squamous
.Sarcomatoid
• The gold standard surgical treatment for patients with UTUC of all
grades and stages has been radical nephroureterectomy with cuff of
bladder + Lymphadenectomy

Kidney Peri-renal fat Gerota fascia En bloc Ureter Cuff of bladder

• Other option:- Kidney sparing approaches Orifice &

intramural ureter
• Low risk disease:-
• Kidney sparing approaches:- Preferred approach, survival is similar to that after RNU & low
morbidity

• The risk of ipsilateral recurrence after conservative treatment of ureteral tumors is 33% to 55%

• The patient should be informed of the need and be willing to comply with an early second-look URS
and stringent surveillance ? Disease
progression

• Seisen, T., et al. Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Nonmuscle Invasive Bladder Cancer Guidelines Panel. Eur Urol, 2016. 70: 1052.
• Indications :-
• Low risk disease

• Solitary kidney, bilateral tumor, CKD, renal insufficiency- C/I for RNU

• Favorable clinical and pathologic criteria - Papillary, unifocal, low-

grade tumor, and size less than 1.5 cm, where cross-sectional imaging
shows no concern for invasive disease
• 1. Endoscopic Management:-
• Ureteroscopy:- Ho:Yag laser or Nd:Yag
• Percutaneous approach ( Inaccessible by URS)
• 2. Ureteral resection:- Segmental ureterectomy

• Offered to low grade, non muscle invasive disease of proximal or mid ureter that is not
amenable to complete ablation by endoscopic means because of tumor size or
multiplicity.

• Distal ureterectomy and neocystostomy may be offered to low grade, low stage or in
select case, high grade, locally invasive tumor of distal ureter when renal preservation is
necessary

• if high-grade disease is present, many practitioners also do an ipsilateral pelvic lymph

node dissection.
• Advantages:- Preserve renal function & providing adequate
pathological specimen - need and extent of adjuvant therapy.

• It is critical to evaluate the entire upper tract above the tumor with
ureteroscopy to ensure there is no multifocality.
• 3. Chemo-ablation:- Treatment with mitomycin gel ( 6 instillation,
once weekly)

• Most appropriate- for solitary residual, low-grade tumor that is low

volume (eg, 5–15 mm) and who are not candidates for or are not
seeking RNU as a definitive treatment.

• 56% complete response after 12 month. (OLYMPUS Trial- Single arm

phase III )
• Adjuvant instillations:- After kidney sparing surgery-

• Antegrade or retrograde instillation of BCG or mitomycin C

• Recent evidence suggests that early single adjuvant intracavitary upper tract
instillation of mitomycin C in patients with low-grade UTUC might reduce the risk of
local recurrence

• Gallioli, A., et al. Adjuvant Single-Dose Upper Urinary Tract Instillation of Mitomycin C After Therapeutic Ureteroscopy for Upper Tract Urothelial Carcinoma: A Single-Centre Prospective
NonRandomized Trial. J Endourol, 2020. 34: 573.
• There is currently no data to support the use of bladder instillation of
chemotherapy after kidney-sparing surgery as available RCTs included
only patients who received RNU.
• High-risk disease:-
• Radical nephroureterectomy with bladder cuff + Lymphadenectomy- STD treatment

• In invasive or large (T3/T4 and/or N+/M+) tumours an open approach is favoured, as the oncological
outcomes may be better as compared to minimally-invasive RNU

• A comparative survival analysis of patients undergoing robotic-assisted versus laparoscopic or open

surgery for upper tract urothelial carcinoma (UTUC)- No survival difference

• Peyronnet, B., 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.
• Simone, G., et al. Laparoscopic versus open nephroureterectomy: perioperative and oncologic outcomes from a randomised prospective study. Eur Urol, 2009. 56: 520.
• Clements, M.B., et al. Robotic-Assisted Surgery for Upper Tract Urothelial Carcinoma: A Comparative Survival Analysis. Ann Surg Oncol, 2018. 25: 2550.
• Lymph node dissection:-

• Template-based and completeness of LND improves CSS in patients

with muscle-invasive disease and reduces the risk of local recurrence

• Lymph node dissection appears to be unnecessary in cases of TaT1

UTUC because of the low risk of LN metastasis, however, tumour
staging is inaccurate pre-operatively; therefore a template-based LND
should be offered to all patients who are scheduled for RNU for high-
risk non-metastatic UTUC
Template for LND :-
• Kidney sparing for high risk tumor:- considered on a case-by-case
basis with imperative indications such as solitary kidney, bilateral
UTUC, chronic kidney disease/severe renal insufficiency or any other
comorbidity compromising the use of RNU .

• However, there is a greater risk of progression

• Segmental resection preferred over endoscopic management

( reliably treat surface tumor only ) for high grade tumor.
• Peri-operative chemotherapy:-
• Neoadjuvant treatments:- No RCT
• Chemotherapy:- The primary advantage of neoadjuvant chemotherapy (NAC) is the
ability to give cisplatin-based regimens when patients still have maximal renal function

• Pathological downstaging and complete response rates at RNU- direct impact on OS

( Retrospective studies )

• No RCTs have been published yet but prospective data from a phase II trial showed
that the use of NAC was associated with a 14% pathological complete response rate in
high grade UTUC.
• Patients with an advanced clinical stage (cT3–4) or with clinically
enlarged lymph nodes (cN+) are potential candidates for neoadjuvant
chemotherapy (NAC),
• Adjuvant treatment:-
• Bladder instillation:-
• The rate of bladder recurrence after RNU for UTUC is 20–50%.( Within
2 years) ( Monoclonal theory ).
• Two prospective randomised trials [ODMIT C trial, THP monotherapy
study group] and two meta-analyses have shown that a single post-
operative dose of intravesical chemotherapy (mitomycin C,
pirarubicin) 2–10 days after surgery reduces the risk of bladder
tumour recurrence within the first years post-RNU- Abosulute
reduction is 11% ( Std of care )
• No direct evidence supporting the use of intravesical instillation of
chemotherapy after kidney-sparing surgery, singledose chemotherapy
might be effective
• Adjuvant Chemotherapy:-

• POUT trial:- phase III trial has demonstrated benefit of adjuvant

therapy for pT2-4, N+ patients. (Largest trial in UTUC, adj chemo- STD
of care)

• Chemotherapy consisted of 4 cycles gemcitabine + cisplatin or

carboplatin
• Adjuvant therapy significantly improved DFS (HR, 0.45; 95% CI, 0.30–
0.68; P = .0001) after a median follow-up of 30.3 months. (Three-year
event-free estimates- 46% vs 71% )
• Immunotherapy:-

• In a phase III, multicentre, double-blind RCT involving patients with

high-risk muscle-invasive UC who had undergone radical surgery,
adjuvant nivolumab improved DFS compared to placebo in the
intention-to-treat population (20.8 vs. 10.8 months) (CheckMate 274)

• Adjuvant chemotherapy is superior to adjuvant Nivolumab

• Laukhtina, E., et al. Chemotherapy is superior to checkpoint inhibitors after radical surgery for urothelial carcinoma: a systematic review and network meta-
analysis of oncologic and toxicity outcomes. Crit Rev Oncol Hematol, 2022. 169: 103570.)
• UTUCs that invade the muscle wall usually have a very poor
prognosis.

• The 5-year specific survival is <50% for pT2/pT3 stage & <10% for pT4
stage
• Surgical mn according to location & risk status:-
• Follow up:-
• After RNU:-
Cystoscopy & cytology – CT –
3monthly X 2 years, 6 monthly X 2 years
6 monthly till 5years Then annually
Annually

• After NNS:-
URS & cytology- Cystoscopy & CT-
Early 2nd look URS- 6-8 3 and 6 months
week Annually till 5
3 and 6 months X 1 year years
6 monthly X 2 years
Annually
• Take home message:-
• Preop staging is inaccurate.
• Combining ureteroscopic biopsy grade, imaging findings, and urinary cytology
may help in the decision-making process between radical nephroureterectomy
(RNU) and kidney-sparing therapy
• As tumour stage is difficult to assess clinically in UTUC, it is useful to “risk
stratify” UTUC between low- and high risk of progression
• In low-risk cancers, NSS is the preferred approach as survival is similar to that
after RNU
• RNU with bladder cuff excision is the standard treatment of high-risk UTUC,
regardless of tumour location
• Template-based and completeness of LND improves CSS in patients
with muscle-invasive disease and reduces the risk of local recurrence
• Adjuvant chemo is std of care in pT2-4, N+.
Thank You