Guide Lines for Management of Bladder Cancer.

1. Guide Lines for Management of Bladder Cancer. Mohamed S. Zaghloul Hussein Khaled Moneir Aboul Ella

2. Essential Work up • History taking & clinical assessment. • Laboratory. • CBC • LFTS : S.albumin, S.bilirubin, prothrombin time, SGOT, SGPT & alkaline phosphatase. • S. Creatinine. • Urinalysis. • Radiologic • Chest x-ray • CT abdomen and pelvis (or IVU ,especially in superficial multifocal tumors + abdominopelvic US) • Bone scan in muscle –invasive tumor.

3. Cystoscopy & EUA: Together with biopsy are mandatory. Describe the cystoscopic features of the tumor including site, number, distance from bladder neck , gross type and associated mucosal lesions. The condition of the urethra and ureteric orifices must be reported upon. Biopsies from the tumor as well as from muscle tissue at its base must be taken. When carcinoma in situ is suspected (positive cytology in absence of gross tumors) random biopsies (at least 4) are taken from bladder mucosa.

4. Staging according to TNM classification(UICC 1997 = AJCC 1997): Regional Lymph Nodes (N) • NX Regional lymph nodes cannot be assessed • NO No regional lymph nodes metastasis • N1 Metastasis in a single lymph node, 2 cm or less in greatest dimension • N2 Metastasis in a single lymph node >2 cm but <5 cm in greatest dimension; • or multiple lymph nodes, none >5 cm in greatest dimension Distant Metastasis (M) • MX Distant metastasis cannot be assessed • MO No distant metastasis • M1 Distant metastasis

5. Treatment • Non-muscle invasive (Superficial) tumors : • a) Ta (G1 or G2 ) : Transurethral Resection (TUR). • b) Ta G3 (high risk of recurrence): TUR + 6 weekly intravesical instillation of BCG started 3-4 weeks after TUR. • c) Tis (precursor for invasiveness): TUR + intravesical instillation of BCG once weekly for 6 weeks. T1 ( G1 or G2, solitary , not associated with Tis ) : Same as Ta (G1 or G2). T1 (G3, multifocal, associated with Tis, vascular invasion or recurrent after BCG): TUR + intravesical instillation of BCG, OR radical cystectomy and bilateral pelvic lymphadenectomy. • * All superficial tumors must undergo monthly FU urine cytology + cystoscopy & TUR every 3 months

6. Treatment Recurrent superficial cases : • TUR and intravesical BCG (6 weekly applications), Radical cystectomy may be performed after the 3rd recurrence

7. Pathological exam of cystoscopic biopsy should include: • Tumor growth pattern • Grade • Evidence of muscle invasion • Multifocality • Presence of associated carcinoma in situ or cell nests of Brunn.

8. Treatment • Muscle invasive tumors (T2, T3 and T4a) Radical cystectomy (cystoprostatovesiculectomy with bilateral pelvic nodal dissection up to the bifurcation of the common iliac LN) together with urinary diversion (continent diversions in suitable patients).

9. The pathological examination of the cystectomy specimen should include: • Tumor type transitional, squamous or adeno. Ca. • Tumor size and multifocality. • Tumor P-stage (TNM, 1997). • Associated conditions Ca. in situ, bilharzial affection. • Number of examined nodes (not less than 10) and number of infiltrated nodes.

10. Treatment • Postoperative radiotherapy (PORT) 5000 cGy/5-5.5 wks using megavoltage machines and 3-fields or box technique including the entire pelvis PORT to start 3-6 weeks after cystectomy . Indications: a) All stages ≥ P2b (P2b-P4a) b) In less advanced stages (P2a) whenever having either G3 or positive LN infilteration. • NB : PORT is also indicated in presence of positive safety margin or gross residual disease

11. Treatment • Adjuvant chemotherapy ,in the form of: 4 courses of Gem-cis , is indicated in : a) P3 and P4 stages b) positive LN c) Grade III

12. Preoperative radiotherapy 4000-5000 cGy/4-5 weeks is indicated in : - previously explored (after previous cystostomies) - T4 explorable.

13. T4b, recurrent or metastatic patients treated by palliative radiotherapy and/or chemotherapy. Gemcitabine 1000 mg/m2 D1 & D8 Platinol 70 mg/m2 D2 This is given with proper hydration and other supportive measures and to be repeated every 21 day.

14. Medically unfit for radical cystectomy or complete refusal of surgery: • Trimodal therapy can be performed in: *Organ confined non-metastatic disease (T2a or T2b) with no Carcinoma in situ (Cis). *No hydronephrosis Procedure: 1. Maximal TUR 2. Three cycles of chemotherapy (Gemcitabine & platinum). 3. Cystoscopic evaluation & biopsy from any residual lesions. A. If Complete remission (CR) another 3 cycles of chemotherapy then radical radiotherapy. B. Less than CR , radical cystectomy (if still medically unfit radiochemotherapy) & postoperative 3 courses of chemotherapy.

15. Medically unfit for radical cystectomy or complete refusal of surgery: (Radical concurrent radiochemotherapy using weekly Gemcitabine (250 mg/m2) or cisplatinum (30mg/m2) may replace sequential chemoradiotherapy as organ preserving radical treatment).

16. Follow-up * Every 2 months in the first year, every 3 months in the 2nd & every 6 months thereafter. * CXR and CT abdomen & pelvis are performed every year. * Bone scan to be performed whenever necessary.

17. Follow up: - At every follow up visit the physician should be able to evaluate: • Tumor response: No evidence of disease, site & size of recurrence; local, bone, chest, liver, …etc. • Immediate & late treatment morbidity including surgery, radiotherapy, chemotherapy or the combination.