Upper Tract Urothelial Carcinoma Aua Review Ch 15

Front 1

What is the most common presenting symptom of UTUC?

Back 1

- Hematuria (75%)
- Flank pain is the presenting sx in 30% and may imply obstruction

Front 2

What are risk factors for developing upper tract UCC?

Back 2

1.Balkan nephropathy - degenerative interstitial nephropathy which accounts for up to 40% of all renal cancers. Does not affect bladder cancer. Increases risk 100-200 fold and more likely to develop bilateral UTUC
2. Smoking - increases risk 3-fold. Risk appears dose related and increases risk of ureteral tumors greater than renal pelvic tumors
3. Coffee consumption
4. Analgesic abuse
5. Exposure to coal, asphalt, tar, petroleum, aniline dyes and other amines
6. Hereditary - Lynch syndrome II associated with colon tumors. It is an AD defect in the DNA mismatch repair genes hMLH1 and hMSH2
7. Cyclophosphamide exposure
8. Chronic phenacetin use (an analgesic similar to aniline)
9. Chronic inflammation
10. Hx of UCC of the bladder - 15-50% of patients with UTUC have bladder cancer

Front 3

What is the peak age incidence and mean age incidence?

Back 3

Peak age incidence is 70-79 years. Mean age is 65 years

Front 4

What is the incidence comparing men and women and blacks and whites?

Back 4

Men are affected twice as often than women; and whites are affected twice as often as blacks

Front 5

Where is the highest incidence of upper tract UCC?

Back 5

Balkan states - may account for up to 40% of all renal cancers

Front 6

Where in the ureter is UCC most common?

Back 6

Lower ureter (70%), then mid (25%) then upper (5%). Invasion is more common in ureter than in bladder

Front 7

how many upper tract UCC are low grade?

Back 7

as with bladder tumors, 55-75% are low-grade and low-stage, and 85% are papillary

Front 8

Is bladder UCC or upper tract UCC more common?

Back 8

Bladder. Upper tract is more often associated with familial syndromes though

Front 9

What % does upper tract UCC account for all UCC

Back 9

5%

Front 10

What % is found in the renal pelvis? Ureter?

Back 10

60% is found in the renal pelvis while 40% is found in the ureter. When UTUC is in the ureter, it usually occurs in the distal ureter

Front 11

What characteristics in bladder cancer increase the risk of UTUC?

Back 11

0. Stage and grade of bladder UCC
1. CIS or HG UCC
2. bladder cancer at the UO, trigone, or bladder neck
3. Multifocal
4. VUR (20 fold increase)
5. UC at the ureteral margin during cystectomy
6. UC in the distal ureter during cystectomy

Front 12

What is the chance of synchronous UTUC in patients with bladder cancer?

Back 12

2.5%

Front 13

What is the chance of metachronous UTUC in pateints with CIS or high grade bladder cancer?

Back 13

20%

Front 14

How many pts with UTUC develop a UCC of the bladder?

Back 14

30-75%. Risk is likely associated with grade, stage, multifocality, CIS and other co-risk factors, such as smoke exposure

Front 15

What is the chance of metachronous UTUC in pateints with papillary or low-grade bladder cancer?

Back 15

1-4%

Front 16

After treatment of UTUC, what is the risk of recurrence in the contralateral upper urinary tract?

Back 16

2-8%

Front 17

Differential diagnosis of an upper tract filling defect

Back 17

1. Radiolucent stone
2. Blood clot
3. Renal papillae
4. Fungus ball
5. Extrinsic vascular compression
6. Renal parenchymal tumor
7. Urothelial cancer
8. Ureteritis/pyelitis cystica
9. TB
10. Benign or traumatic ureteral stricture
11. Endrometriosis

Front 18

What is the gold standard for upper tract UCC for high grade, large, invasive, or multifocal disease?

Back 18

Radical nephroureterectomy with excision of a bladder cuff to include the intramural portion of the ureter

Front 19

What are nephron sparing techinques? When are they indicated?

Back 19

1. Segmental parenchymal resection
2. Segmental ureteral resection with reconstruction
- end to end anastomisis
- direct bladder reimplantation
- reimplantation with bladder hitch or boari flap
- ureteral substitution (ileal ureter)
3. Open pyelotomy with tumor excision and ablation but requires a large extrarenal pelvis and a papillary low grade tumor

Front 20

When is endoscopic treatment a good option?

Back 20

Best reserved for low grade, unifocal lesions of the ureter, renal pelvis or upper pole calyx

Front 21

What are the steps for retrograde URS management?

Back 21

Use forceps or basket to debulk. treat base with fulguration or laser.

Front 22

What are the steps for antegrade management?

Back 22

Establish nephroscopy tract. Biopsy and fulguration. Chemotx through nephrostomy tube. Second look in 2-14 days.

Front 23

Basic principles for instillation tx

Back 23

- Can be performed through nephrostomy tube, retrograde with ureteral catheter, or reflux up an indwelling ureteral stent
- Rule out infection 1st
- Low pressure instillation
- Use BCG, mitomycin, or thiotepa

Front 24

Where are the most common sites of metastasis?

Back 24

lung, liver, bones, and regional lymph nodes

Front 25

Where do recurrences occur after renal sparing therapy?

Back 25

Almost always distal to the location of the original tumor

Front 26

When fulgurating a UTUC tumor, which laser is preferred?

Back 26

- holmium laser is preferred because the depth of penetration is less than 0.5mm and there is less risk for perforation
- commonly used setting is 0.6-1.0 joules at 8-10Hz

Front 27

What are risks for endoscopic treatment?

Back 27

perforation, ureteral stricture, gross hematuria, and infection

Front 28

What should you do if a ureteral stricture occurs?

Back 28

biopsy - it may indicate UTUC recurrence. if it is benign, balloon dilate or incise

Front 29

How to evaluate patient with microhematuria or flank pain suspecte of UTUC

Back 29

1. Laboratory evaluation includes liver and renal function tests, urinalysis and cytologies.
A. Cytology will identify most CIS and high-grade tumors but is often falsely negative with lowgrade
tumors.
B. Upper tract washings may bemore sensitive than voided urine but likewise may be contaminated from the lower urinary tract.
C. Interpretation of cytologiesmay be hampered by contrast materials.

2. Radiographic evaluation
A. Includes the use of IVP, CT urograms and retrograde pyelograms
B. See Differential Dx for filling defects

3. Endoscopic evaluation
A. Ureteroscopy or nephroscopy
B. When combining radiographic evaluations and endoscopy, the diagnostic accuracy of an upper urinary tract defect is approximately 85%–90%.

5. Histologic correlation between ureteroscopic biopsy and final pathology is 78%–90%; however, it is often difficult to get a good specimen given the spatial limitations of small instruments. Therefore, correlation with grade and stage is poor and requires correlation
of endoscopic, cytologic and radiographic features.

Front 30

AJCC 2010 TNM Staging

Back 30

Tx – Primary tumor cannot be staged
T0 –No evidence of primary tumor
Ta –Noninvasive
Tis –Carcinoma-in-situ
T1 – Invades lamina propria
T2 – Invadesmuscularis
T3 – Invades sinus/peri-ureteral fat or renal parenchyma
T4 – Invades adjacent organs

Nodal Staging
N1 – Single node ≤ 2 cm
N2 –Nodes 2< x ≤ 5 cm
N3 –Nodes > 5 cm

Front 31

Laparoscopic/Robotic approaches and open approaches

Back 31

- As with RCC, treatment for upper tract urothelial cancer can be performed in an open or laparoscopic
technique. In choosing the approach, clinical and anatomic factors must be considered as well as the
comfort level and experience of the surgeon.

- Radical nephroureterectomy and nephron sparing techniques are also available for upper tract urothelial
tumors.

- Radical nephroureterectomy with excision of a bladder cuff to include the intramural portion of the
ureter is considered the gold standard for large, high-grade, invasive ormultifocal tumors. Ipsilateral adrenalectomy is not considered necessary.

- Regional lymphadenectomy is usually performed for high-risk tumors as a staging measure. The therapeutic benefit of an extensive lymphadenectomy has not yet been determined butmay ultimately be shown to be of similar value as new data demonstrate in bladder cancer.

- Laparoscopic approaches for upper urinary tract urothelial carcinomas follow the same basic principles
as discussed in RCC. Approaches include:
* Pure laparoscopic trans or retroperitoneal surgery.
* Hand-assisted techniques.

- Management of the distal and intramural portion of the ureter should not be compromised. Options
include:
* Open excision through a low extraction port.
* Aggressive transurethral resection of the ureteral orifice. This should be reserved for proximal, low-grade tumors.
* Intussusception (stripping) technique – after laparoscopic nephrectomy, a previously placed
ureteral catheter is used to intussuscept the ureter into the bladder where it is excised.
* Transvesical laparoscopic ligation and detachment – performed via 2 transvesical ports. The ureter is tented up and looped. A Collins knife is then used to circumscribe the orifice.
* Totally laparoscopic excision – requires laparoscopic detrusor incision with dissection of the intramural bladder cuff

Front 32

When can nephron sparing options be performed and what options are there?

Back 32

- Nephron-sparing approaches should be done for low-grade, low-stage lesions (open or endoscopic), and for relative or absolute indications as with RCC.

- Options include:
• Segmental parenchymal resection.
• Open pyelotomy with tumor excision and ablation. This is an uncommonmeans of treatment and generally requires a large extrarenal pelvis and a papillary low-grade tumor.
• Segmental ureteral resection with reconstruction. The type of reconstruction depends on the location and extent of the tumor, and includes:
* Primary end-to-end ureteral anastomosis.
* Direct bladder reimplantation.
* Reimplantation with bladder hitch or flap.
* Ureteral substitution (ie, ileal ureter).

Front 33

Endoscopic approaches

Back 33

* Ureteroscopy, pyeloscopy and nephroscopy
• Best preserved for low grade, unifocal lesions of the ureter, renal pelvis or upper pole calyx.
• Steps for retrograde ureteroscopicmanagement include:
* Endoscopic evaluation and collection of cytologies.
* Biopsy and definitive treatment.

• Tumor may be debulked with a forceps or basket. The base is then treated with fulgurationor laser. Holmium:Yag laser is safer in the ureter because of its shallower penetration (<0.5 mm). Settings for this laser are energy of 0.6–1 joule with a frequency of 8–10 hertz.
Nd:YAGmay be better in the pelvis. It works by coagulative necrosis and has a deeper penetration (5–6mm). Settings are 5–15 watts for 2 seconds.
• Tumor can be resected with a ureteral resectoscope. Extra care is needed in the mid to upper ureter.

* Antegrade percutaneousmanagement has the advantage of the ability to use larger instruments that can remove a larger volume of tumor. Staging and grading is ordinarily better as well given the amount of tumor that can be removed. Additionally, lower pole tumors aremore easily accessed and topic therapies canmore easily be applied. It is best reserved for larger, more extrarenal pelvices.

• Steps include:
* Establishment of a nephroscopy tract.
* Biopsy and definitive therapy.
* Second look within 4–14 days to allow for adequate healing with rebiopsy and fulguration of the base.

Front 34

Results of endoscopic management:

Back 34

• For retrograde management, the overall recurrence rates are approximately 30% and depend on stage, grade, size and focality.
• Complications of ureteroscopy and their management are similar to endoscopic management of stones.
• Series for antegrademanagement are small. Most low-grade, smaller, unifocal lesions do well. Higher grade, invasive lesions do worse. Nephroscopy tract seeding appears uncommon.

Front 35

Instillation therapy

Back 35

• Can be performed antegrade through a nephroscopy tract, retrograde through a ureteral catheter or by reflux up an indwelling ureteral stent.

• Basic principles include:
* Rule out infection first.
* Low-pressure instillation.

•Most series are small, retrospective, highly selected and not controlled.
• The same agents used in bladder cancer have been used in the upper urinary tracts including BCG, mitomycin and thiotepa.
• The accumulated experience appears encouraging in properly selected patients.
• Most common complication of upper tract instillation is sepsis.

Front 36

Systemic therapy

Back 36

• Small, highly selected series evaluating adjuvant radiation suggest it may decrease local recurrence
but not systemic disease.
• Both induction (neoadjuvant) and adjuvant therapies are reasonable. Neoadjuvant chemotherapy may be a reasonable option for patients with bulky regional adenopathy.
• There are no prospective controlled trials evaluating chemotherapy for upper urinary tract urothelial cancers. Most of the data are extrapolations frombladder cancer series