upper tract transitional cell carcinoma [dr. edmond wong]
DESCRIPTION
Summary ON Upper Tract Transitional Cell CarcinomaTRANSCRIPT
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)