Upper tract UC

Q.

• This investigation was performed on a 61 year old man presenting with hematuria.

                                                                                                               

Q.

• A. What abnormality is shown?

• B. Give 2 treatment options?

Q.

• A. Filling defect at lower part of R ureter

• B. segmental resection of ureter

• Or nephroureterectomy.

Scenario 1

• 70/M

• Gross hematuria

• IVU done

• Cysto : NAD

• DDx ?

• Management plan ?

DDx of filling defect

1. Tumor

2. Stone

3. Fungal ball

4. Clots

5. Sloughed papilla (papillary necrosis)

• URS– Combined with RP : accuracy 90% – Allows biopsy in addition to direct visualisation

and selective or brush cytology sampling to improve the accuracy of urine cytology

– Accepted as the standard of care

CT• Good for detection of gross extraureteral

lesions or distant metastases but not so in staging small lesions

• Johns Hopkins 1996– CT overstages TCC renal pelvis in 32% but CT

staging accurate if hydronephrosis ignored– Hydronephrosis not necessarily mean invasive

disease

Multiphase multidetector CT (MDCT)– Fritz Eur Urol 2006

• MDCT accurately predicts stage of UTUT in 88%

What stage?

• TCC ureter involved periureteric fat: T3

• TCC renal pelvis invading into renal parenchyma: T3

• TCC renal pelvis invades through pelvis into perinephric fat: T3

• TCC renal pelvis through the renal parenchyma into perinephric fat: T4

TCCUT / UTUC : Background

• EAU 2004 GL– 5% of all urothelial cancers– TCC renal pelvis 10% of all renal tumors– Ureteric tumor ~25% of TCCUT

• Most are TCC except fibroepithelial polyp in pediatrics • Distal ureteric TCC more common than upper ureter

– Peak incidence in 50-70s, rarely before 40 and M:F 3:1

– 2% synchronous, 5% metachronous– Commonest presentation as gross / microscopic hem

aturia– No RCT available in any aspects of TCCUT

What are the aetiological risk factors for TCCUT besides those responsible for Ca bladder?

1. Analgesic abuse (phenacetin containing) : asso with pap necrosis

2. Balkan endemic nephropathy (incidence 100-200x usual) : common in 3rd-5th decade of life

3. Chinese herb (Aristolochia fangchii 廣防己 ) : contains aristolochic acid 馬兜鈴酸

4. Blackfoot disease : endemic PVD in Taiwan from sustained exposure of arsenic in well water

5. HNPCC (Lynch II)

• Treatment options :

1. Radical NU

Scenario 2

• 70/M

• Hematuria

• IVU showed renal pelvis tumor

• F-URS Bx : 3cm papillary tumor, G3 UC

• CTU done : no extrarenal disease; contralateral kidney normal

• Plan ?

Radical NU

• Radical Nephroureterectomy with en-bloc excision of intramural ureter and a cuff of periureteric bladder

– First described by Albarran

in 1909– Remains the gold standard

of treatment to date

Why NU?

• EAU 20041.High rates of stump recurrence if left

2.High incidence of ipsilateral multicentricity

3.Low incidence of contralateral metachronus disease

– 15% have a tumour in the opposite kidney on FU

Nephrectomy alone

• Stump recurrence for TCCUT with nephrectomy alone : 42%

NU

• Controversies– ?LND– ?Adrenalectomy– ?Approach – any oncological difference– ?Method of treating the distal ureter– ?Obviate NU (i.e. NSS)– ?Role of adjuvant treatment

• MMC instillation into bladder after nephroureterectomy prevent bladder recurrence

?LND

• For (eg. Skinner)– Adds diagnostic and prognostic information to

disease– Adds little time to procedure and occasionally has

therapeutic value– Similar concepts proven of benefit for Ca Bladder

• Against – LN metastases mean early systemic metastases

and thus of very poor prognosis– Extent of LND not well delineated

?LND

• Tolley 2007 overview– LND has only benefit reported in low-volume

disease (up to N1) – Especially in light of some series of good

survival results • Batata 1976 : 23% 5YS T3-4,N1-2 disease with

radical surgery• Brown 2005 : 2YDSS 95% with N+ disease

?Adrenalectomy

• Traditionally adrenal included in the specimen en-bloc as it is ‘not an infrequent’ site of metasteses

– Adrenalectomy adds little to the cure of UTUT (CW9)

• Adrenalectomy may be indicated if– Invasion into adrenal by tumor– Palpably abnormal on laparotomy– Tumor at superior location (upper pole)

• No available clinical data • Role uncertain

Distal ureter

• All options must consider– Possible seeding of urine from above into the

extravesical space – Adequate removal of intramural ureter

Patient in scenario 2 ((3cm tumor, G3, N0 on CT) agrees to

an open RNU, what is the chance of his survival in 5 yrs?

Results of ONU : Quotable series• Rassweiler meta-analysis 2004 (n~1400)

– Local recurrence 0-15% mean 5%– Distant metastases 0-30%, mean 15%– 5 yr DSS 49-83%, mean 60%

Hall, et al

Stage Disease-specific 5-year survival rate (%)

Ta/CIS 100

T1 90

T2 70

T3 40

T4 <5

Prognostic factors

• Tumor stage (MOST IMPORTANT)• Tumor grade• Location

– T3 renal pelvis tumor 5YS 54% compared with T3 ureteral tumor 24% (Guinan 1992)

• Associated cis upper tract• Lymphovascular invasion • Molecular markers eg. p53• Age and gender

He enquired about any 微創 method of having the NU. Is it bet

ter than the traditional NU?

Laparoscopic Radical Nephroureterectomy

• First performed by Clayman 1991– Multiple series published, each with different

approach (retroperitonoscopic / transperitoneal/ HAL) and different ways to deal with the issue of distal ureter

LNU vs ONU comparative studies

• Rassweiler 2004 meta-analysis of LNU and ONU series incl. 8 comparative series

– In total LNU 377 ONU 969 (only 3 lap series reach 5 yrs FU*; most series 2 yrs FU)

– Similar Bladder, local recurrence and metastases rate 24%, 5% and 15%

– 5 yr survival laparoscopic series higher (LNU 81% vs ONU 61%)

– 1.5% port site metastases (6/377)

* Edinburgh, Nagoya, Heilbronn : no difference in oncological outcome in all 3 series

Edinburgh series• Tolley 7-yr comparative series JU 2004

– 7YDSS LNU 72% ONU 82% – No significant diff between ONU and LNU – Tumor stage and grade predicted risk of met

astases and death

Scenario 3

• 75/F

• Solitary functional left kidney

• Cr 150

• Found to have TCC ureter 1.5cm at mid-third

• CT showed localised disease

• Plan ?

NSS• Initially offered for absolute indications onl

y (solitary kidney, bilateral disease etc)

• More liberal use in relative / elective situations gaining acceptance

• Includes– Open

• Partial nephrectomy / ureterectomy

– Endoscopic• Retrograde ureteroscopic treatment• Percutaneous endoscopic treatment

Open NSS : TCC ureter• Open segmental ureterectomy and UU

– Indications (CW9)• Non-invasive G1-2 tumors of the proximal and midureter

that are not suitable for complete endoscopic ablation under need for NSS (size / multiplicity)

• Invasive / G3 tumors under need for NSS

• Distal ureterectomy and ureteroneocystostomy – Indications (CW9)

• Low grade, low stage distal ureteral tumor not completely removed by endoscopic measns indicated for NSS

• Selected cases of high grade invasive tumors

• Subtotal ureterectomy + ileal ureteral interposition

• Total ureterectomy + renal autotransplantation and pyelocystostomy

Open NSS : TCC ureter

• Risk of ipsilateral recurrences is significant 50%

– Most recurrence occurs distal to lesions– Proximal recurrences are also rarely seen

• Overall 5YS excellent for G1-2 noninvasive tumors

– 5YS ~ 50% for T2 disease but falls dramatically with T3

Endoscopic Treatment

• Can be accomplished with– Electrosurgical means

• Resectoscope (11.5-13.5F)• Electrocautery probe ablation

– Laser• Use Nd:YAG 30W for coagulation (due to its

greater depth of penetration 4-6mm) • Use Ho:YAG (<0.5mm penetration) for tissue

ablation

Ureteroscopic ablation

• Advantages– Low morbidity– Able to be done as out-patient– Potential benefit of a closed system

• Disadvantages– Inability to treat large lesions (>1.5cm)– Potential staging errors – Possibility of pyelolymphatic spread

Tolley’s series• Sowter & Tolley JEU 2007

– 74% recurrence; mean 2.65 recurrences at 12.6m

– 30% required NU; mean time 38m (25% pT0) • Indication : failed endoscopic control, high-grade/ i

nvasive disease

– Renal preservation rate 71%– Bladder recurrence 34%– No patient died directly of TCCUT recurrence– At mean 42m, OS 80%, DSS 100%

Tolley JEU 2007 :

• “… experience reveals that conservative treatment (endoscopic) may be the preferred option in high-risk patients such as those with bilateral disease, solitary kidney, or comorbidities that contraindicated open surgery…..”

• “ ….. our experience adds to the growing evidence in the literature that conservative, endoscopic management of low-grade, low-stage disease in patients with normal contralateral kidneys is a safe and effective approach provided the criteria of vigorous endoscopic follow-up can be met …….. provided there is a low threshold for extirpative therapy.”

NSS Indications

• Indication– Absolute/relative indications (traditional)

• Solitary kidney• Bilateral disease• Background renal impairment• Significant comorbidities precluding major

surgery

– Elective indications only in (Tolley 2007): • Low grade • <1.5cm size• Vigorous endoscopic FU possible

Endoscopic Treatment

• Complication– Perforations 5%– Stricture up to 10% (up to 40% may be due

to recurrent tumor)– Theoretical risk of pyelolymphatic

metastases

Scenario 4

• 80/M

• Cr 170

• Gross hematuria

• IVU as shown

• FC : normal

Percutaneous Resection

• Indication (Tolley)– General endoscopic Tx indications but for :

1. Large tumors of the renal pelvis / proximal ureter (>1.5cm)

2. Tumors in renal pelvis non-accessible even with f-URS (eg lower pole)

Percutaneous Resection

• Advantages– Large working instrument permit

management of larger tumor– Access for adjuvant therapy– Some advantage in dealing with patients

with urinary diversion

• Disadvantages– More morbidity, blood transfusion etc– Risk of tract seedling

Percutaneous Resection

• Techniques– Access into desired calyx beforehand– Large sheath (F30 or above) to keep

intrapelvic pressure to minimum– Energies : Electrocautery/Resection/Laser– Typically require 2nd look within several

days

Percutaneous Resection

• Local recurrence : 50% recurrence

• 20% required ONU (HG / invasive disease)

• DSS 80% – Roupret EU 2007

Percutaneous Resection

• Complications (Tolley review 2007)– Transfusion >20%– PUJ stricture – Pleural effusion– Track seedling

• Only 2 cases have been reported

• Prognostic factors (Tolley review 2007)• Stage, grade

• Location of tumor (ureteral vs renal pelvis)

• Percutaneous resection done

• Postop D1, PCN urine clear

• Question from your trainee ….

• “Can we instillate MMC to decrease recurrence?”

Adjuvant treatment after NSS

1. Instillation of immunotherapeutic / chemotherapeutic agents

– Via• PCN / ureteral catheters / double-J / iatrogenic VUR

– Agents used• Thiotepa, MMC, BCG

– No studies have shown decreased recurrences / improved survival

– Possible reasons• Insufficient number amassed• UTUT has different tumor biology to CaB• Delivery system inadequate with insufficient dwell time and

non-uniform exposure

– Complications• Bacterial sepsis• Systemic absorption (pressure </= 25 cmH20)

2. Brachytherapy to nephrostomy track– Using iridium wire / other delivery

mechanism• Little data to support• Possible complications is pyelocutaneous fistula

Scenario 5

• You are doing an ONU for a TCC mid-ureter ~2cm

• Intraop some desmoplastic reaction to periureteric tissue noted

• OT completed

• Patho : pT3N0

• Any role of adj RT?

Adjuvant RT after NU

• To tumor bed & regional LNs

• Rationale : to decrease local relapse rate for locally advanced disease eg. T3, T4, N+

• Little evidence to show it has survival benefit

• “some benefit in local control” (EAU2004)

Hall

• Retrospective series

• Since there is no diff in survival, RT not considered of survival benefit

Scenario 6

• 60/F

• 1.5cm G1 UC ablated with URS

• How would you FU her ?

Tolley

• Sowter & Tolley JEU 2007– Cystoscopy and URS Q3m until upper tract cl

ear– If no recurrence, Cysto and URS Q6m for 2 yr

s then yearly – Cystoscopy needs to be more frequent if ther

e is concomitant CaB– RP and urine cyto saved during URS

TCC prostate ductTCC prostate duct

TCC prostate ductTCC prostate duct

• Treat effectively by BCG (T) only stromal, or acini not effectively treated

• TUR adequate for control (F)• High recurrence in urethra if left behind (T)

25%• Contraindication to orthotopic replacement.

(T)• PSA is elevated (F)