Transcript Document

A Guide to the Diagnosis, Treatment
and Follow-Up of Bladder and Kidney
Cancer.
Dr Manish Patel MB.BS., MMed., FRACS
Urological Oncologist
Westmead Hospital & Westmead Private Hospital
Senior Lecturer and Director of Urology – University of Sydney
Scientific Director-Urological Cancer Organisation
Urologist to the NSW Cancer Council
Bladder Cancer Incidence is Decreasing in NSW
Risk Factors
• Smoking
• Previous urothelial cancer.
• Exposure to carcinogens
– Aromatic amines
– Benzedine
– Alanine dyes
• Urinary stasis (eg. Diverticulum)
• Chronic infection/irritation (eg. IDC, stone, UTIs)
Bladder Cancer Staging
Tis
Superficial
Invasive
Bladder Cancer Cell Types
• Transitional Cell Carcinoma (TCC) >90%
– 70% are superficial
• Squamous Cell Carcinoma 5%
• Adenocarcinoma 0.5-2%
Progression of Urothelial Cancers
P53/ INK4A
mutations
Normal Urothelium
Papillary High Grade
Hyperplasia
Chromosome 9
P53/ INK4A
mutations
CIS
>40%
80%
Progression
<4%
Muscle Invasive
Papillary Low Grade
Cancer of the Bladder
Signs and Symptoms
Signs and Symptoms
Painless Hematuria
Vesical Irritability
Flank pain or Kidney Failure
Lower extremity swelling
Pelvic Mass
Weight Loss
Abdominal or Bone Pain
Percent of All Patients
85
40
20
10
10
8
5
Screening For Bladder Cancer
Haematuria screening.
• Haematuria does preceed a diagnosis for bladder
cancer by >2 years.
• Cystoscopy is often negative in these early cases.
• However:
– In randomised studies of screening for haematuria, no
benefit has been demonstrated in survival from
bladder cancer.
Algorithm for Bladder Cancer Treatment
First Occurence
TCC
Superficial Disease
Ta, T1
Intravesical
Therapy
TURBT
Follow-Up
Invasive Disease
T2
Progression
Metastatic
Invasive
Chemotherapy
XRT or
Cystectomy
Recurrence
Treatment by P/P
Preference
Instillation of BCG Reduces Recurrence and
Progression of High Grade Bladder Cancers
Instillation of Single Dose Intravesical Chemotherapy
Reduces Recurrences of Superficial Bladder Cancer
Early Cystectomy for Patients with HG Bladder
Cancer Refractory to Intravesical Treatments
Improves Survival
Extended Lymphadenectomy
At Radical Cystectomy
Improves Survival
Greater Number
of Lymph Nodes
Retrieved
Results In
Greater Survival
The Quality of Surgery Affects Survival
The Nerve Sparing Cystectomy
• For the preservation of erectile function.
• Similar principles to the preservation of
cavernous nerves during radical prostatectomy.
• Only possible in selected patients.
• Pioneered at MSKCC and USC.
• Early results: up to 70% potency.
Improvements in Neobladder Results
Ureters
• Better QoL
• Day-time continence
Pouch
96%
• Night-time= 82%
• Females=38% ISC
• Males=5% ISC
Urethra
Outcomes Following Radical Cystectomy
Chemotherapy and Bladder Cancer
MVAC was the standard of care:- Very toxic
Gemcitabine and Cisplatin shown to be equivalent:- much less
toxic.
• Can give as
Neoadjuvant or
Adjuvant therapy
to improve
survival.
• In the metastatic
setting, will
improve survival.
Patterns of Recurrence:
Invasive Disease
Site
Local
Distant
•Bone
•Lung
•Liver
Risk Factors
P3/4=34%, LN+ve=32%
P1/2=20%
P3=60%
P4=70%
LN+ve=40%
Median time
8-18 months
90% recur in
first 3 years.
Upper
Tracts
Generally 2-4%
Ureteral Ca= 30%
17% after RC
6% after neobladder
Up to 45% if TCC in prostate
22-40 months
Urethral
1-3 years
Follow up Schedule After Cystectomy
Evaluation
Year 1
Year 2
Year 3-5
Year 6+
History+ Exam
3mthly
6mthly
6mthly
12mthly
CXR
3mthly
6mthly
6mthly
12mthly
Abdo/Pelvic CT
6mthly
6mthly
6mthly
12mthly
FBC/UEC LFT
3mthly
6mthly
6mthly
12mthly
Urethral Wash
6mthly
6mthly
6mthly
12mthly
Uppertract cytology
3mthly
6mthly
6mthly
12mthly
Other Considerations in FollowUp
• Metabolic complications
– Hypochloraemic hypokalaemic metabolic acidosis.
•
•
•
•
•
•
•
Vitamin B12 and bile acids
Urolithiasis
Pyelonephritis
Preservation of upper tracts.
Potency
Support for stoma or self catheterisation.
Psychological support.
Follow Up Schedule After Superficial Disease
Likely
Likelyhood
hood of
of
progression recurrence
Low Grade 4%
90%
High grade Ta=40%
T1=52%
CIS
>50%
95%
90%
90%
1st Year
2-5 years 6+ years
6
monthly
if 1st
check
clear
3
monthly
6
monthly
yearly
3
monthly
6 monthly
3
3
monthly monthly
6 monthly
Diagnosis, Treatment and Follow-Up of
Kidney Cancer
The Incidence of Kidney Cancer is Increasing
3.1% of male Cancers and 2.4% of female cancers
Approx 50% mortality in NSW.
SIZE MIGRATION
Conventional RCC 1983-1997
9
8
7
6
Mean size5
(cm) 4
3
2
1
0
8.3
7.8
7.1
6.6
5.5
83-85
86-88
89-91
Year
92-94
95-97
Risk Factors
General
• Smoking
• Obesity
• Haemodialysis
• ?Diabetes Mellitus
• ? Hypertension
Genetic
• VHL
• Tuberous Sclerosis
• Burt-Hogg-Dube
• Familial Papillary
• Familial Leimyomatosis
Most Patients are Incidentally Diagnosed.
• Relatively asymptomatic
until large/advanced.
• 25% Metastases at
presentation.
•
•
•
•
Flank pain
Haematuria
Mass
Paraneoplastic
10-30%
50%
<5%
10%
• Paraneoplastic symptoms
–
–
–
–
–
–
–
–
Anaemia
Weight loss
Fever
Hypercalcaemia
Hepatic Sx
Amyloidosis
Enteropathy
Myopathy
30%
33%
30%
10%
5%
5%
3%
3%
MALIGNANT RENAL CELL NEOPLASMS
HeidelbergClassified by Cytogenetics
Type
Occurrence Features
Conventional
Clear Cell
69%
Common, aggressive.
VHL and familial.
Papillary
14%
Often multiple and bilateral
Less aggressive. Assoc. T.S.
Oncocytoma
12%
Benign.
Chromophobe 5%
Less aggressive.
Collecting
Duct
Rare
Very aggressive.
Medullary
Rare
Very aggressive.
Cyctic Masses Have Variable Risk of Harbouring
Cancer: Bosniak Classification.
Bosniak II: Internal septations:
<5% malignant.
Bosniak III: Enhancing rim:
45% Malignant
Bosniak IV: Solid enhancing areas, coarse
calcification
95%-100% Malignant.
TNM Staging of Renal Cell Carcinomas
T1
<7cm
Confined to Kidney
T3b/c
Renal Vein or IVC
T2
>7cm
T4
Outside Gerotas
Fascia
T3a
Adrenal or Gerotas
Fat involved
N: Nodes involved
M: Distant Mets.
Survival: Renal Cell Carcinomas
TNM Stage
T1
T2 or T3a
T3b/c, T4
N or M
The Work Up For A Patient With Suspected Kidney
Mass
Haematuria:
US+/- IVP
Mass
Incidental Mass High Quality
Imaging
CT Abdomen
+/- IV contrast
Surgery
Localised
Staging:
Chest XR/CT
B.S. if high risk
Possible
Cytoreduction
Interferon Tx
Metastatic
Give Choices
Pain/Mass
Palliation
Clinical Trial
Open Radical Nephrectomy
Pros
• Gold standard for cancer
cure.
• Standard for large,
complicated tumours.
• Least intraoperative
complications.
Improvements:
• Small, less invasive
incision- lower
complications.
Cons
• Major operation with
recovery period.
• Higher lung
complications.
Laparoscopic Radical Nephrectomy
Pros
• Less pain
• Quicker recovery
• Lower lung complications
Cons
• Higher intraoperative
complications.
• Can not do large
complicated tumours.
• New procedure- no L/T
data.
• Less kidney conservation.
Partial Nephrectomy Preserves Renal Function
• Preservation of renal
function.
–
–
–
–
Old age
Recurrent tumours
Kidney diseases.
Hyperfiltration
• More difficult surgery
• Slightly higher complication
rate.
• Small tumours
New Technologys for Kidney Cancer
RF ablation and cryoablation
• RF ablating or freezing
tumours under CT
guidance.
• Early results acceptable
for small tumours
• Applicable to elderly
with small tumours.
• Depends on tumour
location.
• No L/T data
Treatment for Metastatic Disease is Poor
• Kidney Cancer is Resistant to Chemotherapy and
Radiotherapy.
• Interferon g- standard of care.
10-15% have temporary response.
• Cytoreduction (removal of primary tumour)
• Can improve survival 4-16months in patients with
good performance status and soft tissue mets.
Future of Advanced Disease
• Kidney Cancers are very vascular.
• Biological therapies aimed at the blood supply of
tumours:
– Antibodies to VEGF
– Thalidomide
• Gene therapy
– Introduce normal genes which are defective in the
cancer, to switch of the increased blood supply to
these tumours.
Recurrence Patterns
Site
Risk
Symptoms
Lung*
3-16%, 54% of all metastases.
Bone
2-8%, 20% of all metastases.
Cough, haemoptysis,
dyspnea
Back, hip rib pain.
Brain
<2%, 5% of all metastases.
Neurologic symptoms.
Liver*
4%
LFTs, CTs
Contralater 1-2% (usually new primary)
al Kidney*
Abdo CT.
Local
* 10%
Recurrence
Abdo CT, loin/back
pain.
*Worthwhile screening as amenable to surgical therapy
Follow Up Protocol
Risk Group
History+Exam CXR
FBC, UEC LFT,
Ca
Abdominal CT
Low
Yearly
Yearly
2 yearly.
Intermediate
6 monthly, then
yearly after 2
years
3 monthly for 2
years, then 6
monthly.
6 monthly, then
yearly after 2
years
3 monthly for 2
years, then 6
monthly.
2 yearly
High
6 monthly for 2
years, then
yearly.
Isolated Renal Fossa, Lung or Liver Recurrence
• Surgical therapy
• Medical therapy
• No therapy
50% survival
14% survival
12% survival
Dr Manish Patel
Urological Oncologist
Senior Lecturer, University of Sydney
Suite 12a
Westmead Private Hospital
Westmead NSW 2145
(Ph) 9633 2088
Suite 3, 2 Redleaf Ave.
Wahroonga NSW 2076
(Ph) 9924 1777