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UROTHELIAL CANCER E. Elamin, MD

UROTHELIAL CANCER E. Elamin, MD. Bladder : Ureters: Renal Pelvis 50 : 3 : 1. Epidemiology. 2005: 63,000 new cases (13,000 death) Male:Female: 3:1 Incidence: increasing (aging) Age: >65 yrs. Risk Factors. Smoking: 80% of cases Occupational: Aniline Dye, Rubber workers, Painters

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UROTHELIAL CANCER E. Elamin, MD

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  1. UROTHELIAL CANCERE. Elamin, MD

  2. Bladder :Ureters:Renal Pelvis • 50 :3 :1

  3. Epidemiology • 2005: 63,000 new cases (13,000 death) • Male:Female: 3:1 • Incidence: increasing (aging) • Age: >65 yrs

  4. Risk Factors • Smoking: 80% of cases • Occupational: • Aniline Dye, Rubber workers, Painters • Drugs: • Phenacetin, oral cytoxan • Upper U tract TCC: 30-50% risk of bladder ca • Bladder TCC: 2-3% risk of Upper U Tract ca • Chronic irritation/infection: • Schistosomiasis, UTIs • Balkan nephropathy

  5. Screening? • Dipstick for microhemturia Messing et al. Urology 45;1995

  6. Clinical presentation • Hematuria (painless) • Irritable bladder symptoms: Tis • Urinary voiding symptoms • Symptoms of advanced dz

  7. Diagnosis • Cystoscopy • Papillary exophytic • Erythema/edema of mucosa: High grade, invasive • IVP, Retrograde pyelogram • Bimanual exam (EUA) • US, CT, Bone scan, MRI

  8. Biopsy • Biopsy of the primary tumor must include muscle if possible • Biopsy of selected mucosal sites to detect possible concomitant Tis

  9. PATHOLOGY • TCC: 90 - 95% • Sq CC: 3 - 7% • Renal pelvis and ureters • Adeno: < 3% • Trigone • Dome: Urachal

  10. Carcinoma in Situ • Usually accompany higher Disease stage • Multifocal • Considered Aggressive if: • Associated with superficial tumors • Diffuse

  11. PROGNOSTIC FEATURES • Grade • TNM stage • T2 (Muscle invasion): 20-50% 5YS • N +ve: 0-20% 5YS

  12. Tx Primary tumor cannot be assessed T0 No evidence of primary tumor Ta Noninvasive papillary tumor Tis Carcinoma in situ: “flat tumor” T1 Tumor invades subepithelial connective tissue T2 Tumor invades muscle pT2a Tumor invades superficial muscle (inner half) pT2b Tumor invades deep muscle (outer half) T3 Tumor invades perivesical tissue pT3a Microscopically pT3b Macroscopically (extravesical mass) T4 Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall T4a Tumor invades prostate, uterus, vagina T4b Tumor invades pelvic wall, abdominal wall Nx Regional lymph nodes cannot be assessed N0 No regional node involvement N1 Metastasis in a single node, ≤ 2 cm in greatest dimension N2 Metastasis in a single node, > 2 cm but ≤ 5 cm in greatest dimension; or multiple lymph nodes, none > 5 cm in greatest dimension N3 Metastasis in a lymph node, > 5 cm in greatest dimension Mx Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Stage grouping Stage 0a Ta N0 M0 Stage 0is Tis N0 M0 Stage I T1 N0 M0 Stage II T2a N0 M0 T2b N0 M0 Stage III T3a N0 M0 T3b N0 M0 T4a N0 M0 Stage IV T4b N0 M0 Any T N1-N3 M0 Any T Any N M1 TNM staging

  13. NON-INVASIVEWork-up • Imaging of upper tract collecting system • Cytology x 1 • Consider pelvic CT before TURBT if sessile or high grade

  14. NON-INVASIVE • Examination Under Anesthesia (bimanual) • TURBT • If sessile, high grade or suspicious for CIS: • Random biopsy • Consider TUR biopsy of prostate

  15. Muscle-invasivework-up • CBC, CMP • Chest x-ray • Imaging of upper tract collecting system • Abdominal/pelvic CT or MRI • Examination under anesthesia/cystoscopy • TURBT • Bone scan if alkaline phosphatase elevated or symptoms

  16. METASTATICwork-up • CBC, CMP • Chest CT • Abdominal/pelvic CT or MRI • Bone scan • ECG • Creatinine clearance

  17. TREATMENT

  18. Superficial Disease • Papillary noninvasive (Ta) and T1: • Few lesions: • TUR • 5 yr Survival rate: 70% • Multiple, >5 cm, Recurrent, +CIS: • TUR +

  19. Papillary or solid • cTa, G1-2: • Observe or • Single dose intravesical chemo within 24 hours (not immunotherapy) • Cystoscopy at 3 m • increasing interval as appropriate

  20. Papillary or solid • cTa, G3 and cT1, G1-2: • Observe or intravesical chemo • BCG (preferred) or Mitomycin • cT1, G3: • Uncertain complete resection based on: • Size/location • No muscle in specimen • Inadequate staging • Lymphovascular invasion • Reresect or Cystectomy: • If –ve: BCG or Mitomycin • If +ve BCG or Cystectomy • Completely resected: • BCG or Mitomycin or • Consider cystectomy

  21. Any CIS/Tis(abnormal mucosa) • BCG • Cystoscopy and urine cytology q 3 m for 2 y • Then q 6 m for 2 y • then annually • Imaging of upper tract collecting system q 1–2 y • Urinary urothelial tumor markers (optional)

  22. Intravesical Treatment • Indications: • Multiple T1 • Multifocal Ta, (G2-3) • Diffuse Tis • Rapidly recurring dz • Cytotoxic agents: Mitomycin, Adriamycin, Thiotepa • Reduce recurrence rate • Immune modulator: BCG (Tis) • Decrease progression rate

  23. ? Cystectomy for Superficial Dz • Large tumors • Some high G • Impractical TUR • multiple tumors • Multiple recurrences • Diffuse Tis unresponsive to intravesical therapy • Prostatic stromal involvement

  24. POST-TREATMENT Ta, T1, CISPERSISTANT OR RECURRENT DISEASE • Cystoscopy +ve: • TURBT  Adj therapy based on tumor and G • Cytology positive, Imaging negative, Cystoscopy –ve: • Random bx: • -ve: Follow-up q 3 m or Maintenance BCG • +ve: BCG (maintenance BCG, if complete response) • If incomplete response: • Cystectomy or • Other intravesical chemo or immunotherapy

  25. Recurrence post-intravesical treatment with BCG or MMC; no more than 2 consecutive cycles • CR  Maintenance BCG (optional) • Tis or Ta: • Change intravesical agent or • Cystectomy • T1G3: • Cystectomy

  26. Papillary or solidF/U • Cystoscopy and urine cytology q 3 m for 2 y • Then q 6 m for 2 y • then annually • Imaging of upper tract collecting system q 1–2 y • Urinary urothelial tumor markers (optional)

  27. PROBABILITY OF RECURRENCE AND PROGRESSION

  28. Invasive Cancer • Cystectomy • Partial cystectomy: • Single tumor without CIS • Radical cystectomy • Overall 5-ys S: 50% • Recurrence rate: 10-20% • Bladder preservation: • TURBT → RT/Chemo • Salvage Cystectomy

  29. cT2TREATMENT • Radical cystectomy • consider neoadj chemo in selected pts • Consider adj chemo if no neoadj treatment given (+ve LN, pT3) • Segmental cystectomy (solitary lesion in a suitable location; no CIS) • Consider adj RT or chemo (+ve LN, +ve margin, high G, pT3)

  30. cT2TREATMENT • Selective bladder sparing following maximal TUR (only if no hydronephrosis); Chemotherapy/RT • Evaluate with cystoscopy and TURBT • +ve: Radical cystectomy • -ve: Observation and/or Chemo/RT and/or Adj chemo

  31. cT2TREATMENT • Highly selected pts with extensive comorbid diseases or poor PS: • TURBT alone or RT alone or Chemo alone: • Evaluate with cystoscopy and TURBT • +ve: Radical cystectomy • -ve: Observation and/or Chemo+ RT and/or Adj chemo

  32. If TURBT alone • Aggressive re-resection of the site within 4 weeks of the primary procedure to ensure that there is no residual disease. • If the repeat TURBT is -ve, repeat cysto every 3 months until a relapse is documented.

  33. RT or Chemotherapy alone is not considered adequate and standard without additional treatment to the bladder and remains investigational

  34. cT3, N0 • Radical cystectomy, consider neoadj chemo: • Consider adj chemo (pT3, +ve LN) if no neoadj treatment given • Selective bladder sparing following maximal TURBT; chemo/RT: • cystoscopy, cytology and TURBT • -ve: Observe and/or Consolidation chemo/RT and/or Adj chemo • +ve: Cystectomy or salvage therapy

  35. Bladder-sparing • Reasonable alternative to cystectomy for pts: • who are medically unfit for surgery • who seek an alternative • No hydronephrosis. • Mets must be excluded. • Complete TURBT as safely as possible • Exam Under Anesthesia

  36. Muscle-invasiveConcurrent ChemoRT • Complete TURBT • Induction ohase: • 40 Gy of external beam RT + Two doses of cisplatin on weeks 1 and 4. • Repeat cysto: • If residual disease, a cystectomy is advised. • If is no visible disease and the cytology and biopsy are negative (T0): • Add 25 Gy of external-beam RT + one dose of cisplatin. • 70% of pts were rendered tumor-free in the bladder at the initial post-treatment cystoscopy exam. • About 1/4 developed a new superficial or invasive lesion requiring additional therapy

  37. cT4a - T4b, N0 • Chemo or Chemo/RT: • Good response: Consider consolidation chemo +/-RT or Surgery • Surgery ± chemo (select cT4a pts only)

  38. NeoAdj Chemotherapy • MVACx2->surg ->MVACx3 or • Surgery -->MVACx5 • 58% DFS • SWOG 8710: Neoadj MVACx3 vs cystectomy: • 5YS: 57% vs 42% • MS: 6.2 vs 3.8Y

  39. Always biopsy enlarged LN if technically possible and no distant mets.

  40. Muscle invasiveF/U • LFTs, Cr, electrolytes, C-x-ray q 6-12 m • Collecting system imaging at baseline and q 2 y • CT at baseline and q 3-6 m for 2 y, then as indicated • If bladder sparing: • cystoscopy + cytology ± biopsy q 3 m x 4, then increasing intervals • If cystectomy: • urine cytology q 6-12 m • If cystectomy + cutaneous diversion: • urethral wash cytology q 6-12 m • If cystectomy + continent orthotopic diversion: • Vit B12 annually

  41. Muscle invasiveRECURRENCE • Local recurrence, Preserved bladder: • Invasive: • Cystectomy or salvage chemo or • RT or • Palliative TURBT • Tis, Ta, or T1: • Intravesical BCG or • cystectomy

  42. Muscle invasiveRECURRENCE • +ve cytology, Preserved bladder (Cystoscopy, EUA, random biopsy -ve): • Retrograde selective washings of upper tract, prostatic urethra biopsy • Metastatic or local recurrence postcystectomy: • Chemo and/or RT

  43. Relapses in the Bladder After Bladder-Sparing Approaches • Invasive disease: • 2nd attempt of bladder preservation is not advisable. • Radical cystectomy: • Salvage cystectomy may not be possible for pts who has received a full course RT (> 65 Gy) and has bulky residual disease. • salvage non-cross-resistant chemo is advised

  44. Mets: pN +ve • Chemo or Chemo/RT: • Cystoscopy: • -ve: Observe or Boost with RT or Surgery • +ve: Salvage therapy

  45. High Risk/Locally Advanced(T3-4, vascular invasion, N+ve) • Cystectomy; 20-30% cure rate • MVACx2 →Surg → MVACx3 • Surg → MVAC • 58% DFS

  46. Mets: Disseminated • Chemotherapy

  47. ChemotherapyMetastatic Disease • CisCA: • MVAC: RR=39% • MVAC vs CisCA: • RR = 65% vs 46% • CMV • Cisplatin • Taxol: RR=42% • CarboTaxol: RR=52% • Gemzar: RR=27% • Gemzar/Cis: RR=66% • TaxolCisIfex:

  48. NON-TRANSITIONAL CELL CARCINOMA (TCC) • Same as TCC management with the following issues: • Mixed Histology: • Complete response less likely with bladder sparing • Pure Squamous: • Cystectomy or RT • Adenocarcinoma: • MVAC ineffective • Cystectomy or partial cystectomy • Consider 5-FU-based therapy • Urachal tumors require complete urachal resection • Small-cell: • Neoadjuvant or adjuvant small-cell chemo regimens • Local treatment (surgery, RT)

  49. PRINCIPLES OF CHEMOTHERAPY • MVAC: • Toxicities limit its use • Historical standard of care based on improved survival and response rates when compared to older regimens. • Gemcitabine/cisplatin • Not inferior to MVAC in terms of survival. • Favorable toxicity profile. • standard 1st choice for most pts. • Alternative Regimens • Cisplatin/paclitaxel • Gemcitabine/paclitaxel • Carboplatin/paclitaxel

  50. PRINCIPLES OF CHEMOTHERAPY • Adj: At least 4 cycles of a cisplatin-based chemo (eg. M-VAC). • Adj for High Risk pts: • T2 tumors with nodal involvement • high-G • transmural invasion, or vascular invasion • P53 positive • No data support the use of adj chemo for non-TCC, regardless of stage.

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