Discuss the pathology of bladder cancers
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Transcript of Discuss the pathology of bladder cancers
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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
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Pathology of bladder cancer Epidemiology Risk factors Clinical manifestation Pathology Staging
Management of muscle invasive bladder cancer
Clinical features Investigation Imaging TURBT
OUTLINE
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Definitive Treatment Radical cystectomy Partial cystectomy Neo-adjuvant / Adjuvant chemotherapy Definitive Chemo-radiotherapy Palliative chemo-radiotherapy.
Prognosis Surveillance/Follow up
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…so that's the problem…
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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
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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
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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
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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.
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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
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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.
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90-95% transitional-cell carcinoma
3% squamos-cell carcinoma 2% adenocarcinoma <1%small-cell carcinoma
99% primary tumors
Bladder cancer:Histology
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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
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Field Cancerisation
Whole urothelium exposed to carcinogen
Transforms independent separate groups of cells
Multiple tumors which are genetically unrelated
Metachronous / Synchronous Disease
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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
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Staging
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Management of a 55 year old man found on
cystoscopy for hematuria to have a suspected
muscle invasive bladder cancer
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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
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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
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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
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Start treatment after full metastatic work up Treatment options:
Radical CystectomyPartial CystectomyNeo-adjuvant/Adjuvant ChemotherapyDefinitive Chemo-Radiotherapy
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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
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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
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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
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Early Urinary Leakage Lymphatic Leakage
Late Recurrent UTI Ureteric stricture Bladder neck stenosis
Complications of Surgery
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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
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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
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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
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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
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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
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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
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Acute effects:Tiredness, cystitis, diarrhea, loss of local hair, skin reddening, Dysuria,Urgency, Frequency
Radiation Toxicity
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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
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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
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Thank you for Listening