A Guide to the Diagnosis, Treatment A Guide to the Diagnosis, Treatment and Follow-Up of Bladder and Kidney and Follow-Up of Bladder and Kidney
Cancer.Cancer.
Dr Manish Patel MB.BS., MMed., FRACSDr Manish Patel MB.BS., MMed., FRACS
Urological Oncologist Urological Oncologist Westmead Hospital & Westmead Private Hospital Westmead Hospital & Westmead Private Hospital
Senior Lecturer and Director of Urology – University of SydneySenior Lecturer and Director of Urology – University of SydneyScientific Director-Urological Cancer OrganisationScientific Director-Urological Cancer Organisation
Urologist to the NSW Cancer Council Urologist to the NSW Cancer Council
Bladder Cancer Incidence is Decreasing in NSW
Risk FactorsRisk 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 StagingBladder Cancer Staging
Superficial
Invasive
Tis
Bladder Cancer Cell Types
• Transitional Cell Carcinoma (TCC) >90%– 70% are superficial
• Squamous Cell Carcinoma 5%
• Adenocarcinoma 0.5-2%
Progression of Urothelial Cancers
Normal Urothelium
CIS
Muscle Invasive
Papillary High Grade
Papillary Low Grade
Hyperplasia
P53/ INK4Amutations
80%Progression
Chromosome 9
P53/ INK4A mutations
>40%
<4%
Cancer of the Cancer of the BladderBladderSigns and Signs and SymptomsSymptoms
Signs and SymptomsSigns and Symptoms Percent of All Patients
Painless Hematuria 85Vesical Irritability 40Flank pain or Kidney Failure 20Lower extremity swelling 10Pelvic Mass 10Weight Loss 8Abdominal or Bone Pain 5
Screening For Bladder CancerHaematuria 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
Intravesical Therapy
Recurrence
TURBT
Progression
InvasiveMetastatic
Treatment by P/P Preference
XRT or Cystectomy
Follow-Up
Superficial Disease Ta, T1
Invasive Disease T2
Chemotherapy
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 LymphadenectomyAt 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
• Better QoL
• Day-time continence 96%
• Night-time= 82%
• Females=38% ISC
• Males=5% ISC
Pouch
Ureters
Urethra
Outcomes Following Radical Cystectomy
Chemotherapy and Bladder Cancer
• Can give as Neoadjuvant or Adjuvant therapy to improve survival.
• In the metastatic setting, will improve survival.
MVAC was the standard of care:- Very toxicGemcitabine and Cisplatin shown to be equivalent:- much less toxic.
Patterns of Recurrence:Invasive Disease
Site Risk Factors Median time
Local P3/4=34%, LN+ve=32% 8-18 months
Distant
•Bone
•Lung
•Liver
P1/2=20%
P3=60%
P4=70%
LN+ve=40%
90% recur in first 3 years.
Upper Tracts
Generally 2-4%
Ureteral Ca= 30%
22-40 months
Urethral 17% after RC
6% after neobladder
Up to 45% if TCC in prostate
1-3 years
Follow up Schedule After CystectomyEvaluation 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 DiseaseLikely hood of progression
Likelyhood of recurrence
1st Year 2-5 years 6+ years
Low Grade 4% 90% 6 monthly if 1st check clear
6 monthly
yearly
High grade Ta=40%
T1=52%
95%
90%
3 monthly
3 monthly
6 monthly
CIS >50% 90% 3 monthly
3 monthly
6 monthly
Diagnosis, Treatment and Follow-Up ofDiagnosis, Treatment and Follow-Up ofKidney CancerKidney Cancer
The Incidence of Kidney Cancer is Increasing
3.1% of male Cancers and 2.4% of female cancersApprox 50% mortality in NSW.
0
1
2
3
4
5
6
7
8
9
83-85 86-88 89-91 92-94 95-97
SIZE MIGRATIONConventional RCC 1983-1997
Mean sizeMean size(cm)(cm)
YearYear
8.37.8
7.16.6
5.5
Risk FactorsRisk FactorsGeneral• Smoking• Obesity• Haemodialysis
• ?Diabetes Mellitus • ? Hypertension
Genetic• VHL• Tuberous Sclerosis• Burt-Hogg-Dube• Familial Papillary• Familial Leimyomatosis
Most Patients are Incidentally Diagnosed.Most Patients are Incidentally Diagnosed.
• Relatively asymptomatic until large/advanced.
• 25% Metastases at presentation.
• Flank pain 10-30%• Haematuria 50%• Mass <5%• Paraneoplastic 10%
• Paraneoplastic symptoms– Anaemia 30%
– Weight loss 33%
– Fever 30%
– Hypercalcaemia10%
– Hepatic Sx 5%
– Amyloidosis 5%
– Enteropathy 3%
– Myopathy 3%
MALIGNANT RENAL CELL NEOPLASMSHeidelbergClassified by Cytogenetics
Type Occurrence Features
ConventionalClear Cell
69% Common, aggressive.VHL and familial.
Papillary 14% Often multiple and bilateralLess 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 CarcinomasT1 T3b/c<7cm Renal Vein or IVCConfined to Kidney
T2 T4>7cm Outside Gerotas Fascia
T3a N: Nodes involvedAdrenal or Gerotas M: Distant Mets.Fat involved
Survival: Renal Cell CarcinomasTNM Stage
N or M
T3b/c, T4
T2 or T3a
T1
The Work Up For A Patient With Suspected Kidney Mass
High Quality CT Abdomen+/- IV contrast
Staging:Chest XR/CTB.S. if high risk
Surgery
Give Choices
Palliation Clinical Trial
Interferon TxIncidentalImaging
Haematuria:US+/- IVP
Pain/Mass
Mass
Mass
Localised
Metastatic
PossibleCytoreduction
Open Radical NephrectomyOpen Radical NephrectomyProsPros• Gold standard for cancer
cure.• Standard for large,
complicated tumours.• Least intraoperative
complications.
Improvements:• Small, less invasive
incision- lower complications.
ConsCons• Major operation with
recovery period.• Higher lung
complications.
Laparoscopic Radical NephrectomyLaparoscopic 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 FunctionPartial 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 CancerRF 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 PoorTreatment for Metastatic Disease is Poor• Kidney Cancer is Resistant to Chemotherapy and
Radiotherapy.
• Interferon 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 DiseaseFuture 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 PatternsSite Risk Symptoms
Lung* 3-16%, 54% of all metastases. Cough, haemoptysis, dyspnea
Bone 2-8%, 20% of all metastases. Back, hip rib pain.
Brain <2%, 5% of all metastases. Neurologic symptoms.
Liver* 4% LFTs, CTs
Contralateral Kidney*
1-2% (usually new primary) Abdo CT.
Local * Recurrence
10% Abdo CT, loin/back pain.
*Worthwhile screening as amenable to surgical therapy
Follow Up ProtocolRisk Group History+Exam
FBC, UEC LFT, Ca
CXR Abdominal CT
Low Yearly Yearly 2 yearly.
Intermediate 6 monthly, then yearly after 2 years
6 monthly, then yearly after 2 years
2 yearly
High 3 monthly for 2 years, then 6 monthly.
3 monthly for 2 years, then 6 monthly.
6 monthly for 2 years, then yearly.
Isolated Renal Fossa, Lung or Liver RecurrenceIsolated Renal Fossa, Lung or Liver Recurrence
• Surgical therapy 50% survival
• Medical therapy 14% survival
• No therapy 12% survival
Dr Manish PatelUrological Oncologist
Senior Lecturer, University of Sydney
Suite 3, 2 Redleaf Ave.
Wahroonga NSW 2076
(Ph) 9924 1777
Suite 12a
Westmead Private Hospital
Westmead NSW 2145
(Ph) 9633 2088