DISCUSS THE PATHOLOGY OF BLADDER CANCERS.

A 55 YEAR OLD MAN IS FOUND ON CYSTOSCOPY FOR HEMATURIA TO HAVE A SUSPECTED MUSCLE INVASIVE BLADDER CANCER.DISCUSS IN DETAILS THE MANAGEMENT OF THIS PATIENT

ByDR BADMUS A.M

Pathology of bladder cancer Epidemiology Risk factors Clinical manifestation Pathology Staging

Management of muscle invasive bladder cancer

Clinical features Investigation Imaging TURBT

OUTLINE

Definitive Treatment Radical cystectomy Partial cystectomy Neo-adjuvant / Adjuvant chemotherapy Definitive Chemo-radiotherapy Palliative chemo-radiotherapy.

Prognosis Surveillance/Follow up

…so that's the problem…

4th most common CA in men, 9th in women, Annual New Cases = 68,810 (51,230 in Male

& 17,580 in Female) M:F = 3:1 Annual Deaths = 14,100 (7,750 in Male &

4,150 in Female)

EPIDEMIOLOGY

Age, Gender, Race Cigarette smoking (2-4x higher relative risk) Exposures to environmental carcinogens:

Occupational -Polycyclic aromatic hydrocarbons, benzene, exhaust from combustion gases, aryl amines

dry cleaners; manufacturers of preservatives, dye, rubber, & leather; pesticide applicators; painters; truck drivers; hairdressers; printers; machinists

Risk Factors for Bladder CA

Pelvic radiation therapy Arsenic (eg. in drinking H2O) Infections

Schistosoma haematobium (N Africa) Increased risk for squamous & transitional cell carcinoma

Chronic UTIs, chronic bladder stones, indwelling Foleys increased risk for squamous cell CA

Other Prior h/o bladder CA

Low fluid intake (increased exposure to carcinogens via decreased bladder emptying)

Genetics (e.g., Retinoblastoma gene)

Bladder birth defects (e.g., persistent urachus) increased risk for adenocarcinoma.

Hematuria (80-90%) –Generally painless and gross hematuria

However, 20% can have only microscopic hematuria

Other urinary symptoms Frequency, urgency, nocturia Pain (less common & often reflects tumor

location)

Clinical features

Lower abdominal pain –Bladder mass Rectal discomfort & perineal pain –Invasion

of prostate or pelvis. Flank pain -Obstruction of ureters Lower extremity edema from iliac vessel

compression, Physical: occasionally an abdominal or

pelvic mass may be palpable.

90-95% transitional-cell carcinoma

3% squamos-cell carcinoma 2% adenocarcinoma <1%small-cell carcinoma

99% primary tumors

Bladder cancer:Histology

Tumor Suppresor gene on Ch 9 - earliest The loss of TS gene p53 on Ch 17 for NIBC to MIBC P53 accumulation in nucleus is an independent

bad prognostic factor Aneuploid DNA content in NIBC, more risk for

progression Immunohistochemistry for microvessel density,

marker for Tr angiogenesis

Molecular Genetics

Field Cancerisation

Whole urothelium exposed to carcinogen

Transforms independent separate groups of cells

Multiple tumors which are genetically unrelated

Metachronous / Synchronous Disease

Clonality

Single carcinogenic insult to a single cell

Clones from this cell spread thro out the UB

Topographically distinct lesions but genetically related

Metachronous / Synchronous Disease

Staging

Management of a 55 year old man found on

cystoscopy for hematuria to have a suspected

muscle invasive bladder cancer

Lower abdominal pain –Bladder mass Rectal discomfort & perineal pain –Invasion

of prostate or pelvis. Flank pain -Obstruction of ureters

Lower extremity edema from iliac vessel compression,

Physical: occasionally an abdominal or pelvic mass may be palpable.

Additional clinical features

Cystoscopy◦ EUA ( Examination Under Anesthesia)◦ Transurethral Resection of the Bladder Tumors ( TURBT)◦ Biopsies

Ultrasound kidneys/abdomen

CT scan/MRI scan ◦ Differential diagnosis◦ Staging ( In muscle invasive disease, CT abdomen must always

be performed for staging prior to making treatment decisions)

Bone scan if symptomatic or raised alkaline phosphatase

Investigations

Bimanual examination under anesthesia If mass palpable : invasive Mobile mass : T3 Fixed mass : T4

Sample muscle within the area of tumor to assess invasion

Sample biopsies from multiple sites and prostatic urethra to r/o CIS only if high grade/sessile/in bladder neck

TURBT

Start treatment after full metastatic work up Treatment options:

Radical CystectomyPartial CystectomyNeo-adjuvant/Adjuvant ChemotherapyDefinitive Chemo-Radiotherapy

Cysto-prostatectomy + Urinary diversion procedure + Pelvic Lymph Node Dissection

Advocates of Surgery argue that:1. There is good long term survival rates2. Morbidity and mortality due to surgery

have now decreased3. Provides for accurate pathological T and N

staging

Radical Cystectomy

Urinary Bladder, Prostate, Seminal Vesicles, Visceral peritoneum, peri-vesical adipose tissue and lower ureter

Followed by a Urinary diversion procedure

Orthotopic Neobladder(Anastomosed to remaining distal urethra)

Radical Cystectomy

Extended pelvic LN dissection is beneficial

Remove all first echelon nodes the hypogastric, obturator, internal and external iliac, pre sciatic and pre-sacral LN

Also extended to include common iliac, lower para-aortic, para-caval, intra- aortic lymph node

Pelvic LN Dissection

Early Urinary Leakage Lymphatic Leakage

Late Recurrent UTI Ureteric stricture Bladder neck stenosis

Complications of Surgery

Done when invasive tumor can be removed with a 2 cm margin of normal mucosa without compromising continence or capacity.

Most common site where it can be done is Dome

Contraindicated at neck and trigone LN dissection should also be done

Partial Cystectomy

Advantages :1. Invivo drug sensitivity testing2. Shrinks down tumor for easier surgery3. Delivers full dose of systemic

chemotherapy upfront thus addressing micro-metastatic disease early

Neo-adjuvant Chemotherapy

Chemo regimenMethotrexate 30mg/m2 D1, D15, D22Vinblastine 3mg/m2 D2, D15, D22Doxorubicin 30mg/m2 D2Cisplatin 70mg/m2 D2

Median survival 77 months in the chemo arm vs 46 months in the surgery alone arm

Not enough evidence supporting adjuvant chemo in bladder cancer

It is justified in patients with high risk for relapse, if neoadjuvant chemo was not given

1. T3 or more2. Node positive3. LVI present4. >20% cells are positive for p53

Adjuvant Chemotherapy

No strong evidence supporting RT in the adjuvant setting

Maybe given in cases of high risk for loco-regional relapse :

1. Positive surgical margins2. Tumor spillage 40-45 Gy ± Cisplatin , if no NAC was given

Adjuvant RT

1. T2 to T3a2. Node negative3. Disease at or near ureteric orifice4. No trigone involvement5. Unifocal dis6. No extensive CIS7. Complete TURBT8. Good bladder function

Ideal Candidates for CCRT

Acute effects:Tiredness, cystitis, diarrhea, loss of local hair, skin reddening, Dysuria,Urgency, Frequency

Radiation Toxicity

Late effects:Chronic cystitis ,Hemorrhagic cystitis, Bladder contracture, Rectal stricture, Small bowel obstruction, bladder telangiectasia (5%), fibrosis and shrinkage, altered bowel habit (<50%), proctitis (5%), impotence (20-30%), incontinence (1%)

79% of patients had normal bladder function at 10 yrs

Radiation toxicity

Stage specific follow up protocol Seen every 6 months for the first one year,

then annually if pT2 or every 3 months for the first 3 years if pT3 tumor.

Assessment involve history, physical examination, chest radiograph, LFT and alkaline phosphatase.

Follow up

Thank you for Listening