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