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Bladder Cancer Guidelines
A Brief Review

Waleed A. Hassen M.D.
Chairman of Urology
Tawam Hospital
Assistant Professor
Johns Hopkins Medical Institutions
Estimated new cancer cases.
10 leading sites by gender, US, 2000




               38 300
                        14 900
Understanding Pathology
    WHO/ISUP 1998 Consensus WHO 2004


• Papilloma
• Papillary urothelial neoplasm of low
  malignant potential (PUNLMP)
• Urothelial Carcinoma low-grade
• Urothelial Carcinoma high grade *
  – Previously classified grade 2 now high grade
Understanding Pathology
                 Recurrence vs Progression


Pathology             5 yr Recurrence   Prob. Muscle
                                        Invasion
Ta, Low grade         50%               Minimal

Ta, high grade        60%               Moderate

T1, low grade         50%               Moderate
(rare)
T1, high grade        50-70%            Moderate-High

Tis                   50-90%            High
Understanding Pathology
            Pathologic Reporting


• Pathology report must comment:
  – Histologic grade
  – The presence of muscularispropria, and degree
    of involvement
  – Presence or absence of LVI
  – Presence or absence of CIS
Understanding Pathology
 Pathologic Reporting
Understanding Pathology
                  Risk (NMIB)


• Low risk
  – Initial Low grade, <3cm lesion


• Intermediate
  – Low grade recurrent, multiple lesions, >3 cm


• High
  – Any high grade or CIS
Staging


• Initial suspicion of TCC
  – Office cystoscopy
  – Cytology
• Suspect NMIBC
  –   Image upper tracts
  –   Pelvic CT before TURBT
  –   EUA
  –   Mapping biopsies if indicated
Staging


• Suspect Muscle Invasive Disease
  –   CBC, Chemistry including AlkPhos
  –   CXR or CT Chest
  –   Upper tract imaging
  –   CT or MRI
  –   Bone Scan if Alk. Phos elevated or symptoms
Transurethral Resection


• Goals of TUR:
  – Complete resection of all visible tumor when
    possible
  – Adequate mapping of bladder if needed
  – Adequate staging by ensuring presence of
    muscle
Management


• cTa (low grade)
  – Complete resection
  – Observation vs single dose intravesical
    chemotherapy*
Management


• cTa (high grade)
  –   Complete resection
  –   Re-resection if no muscle in specimen*
  –   Induction Immunotherapy
  –   Chemotherapy only if unable to tolerate BCG
Management


• cT1 (high grade)
  – Complete resection
  – Strongly advise re-resection
  – Consider early cystectomy especially if re-
    resection shows higher stage or volume disease
  – Induction BCG otherwise
  – Chemotherapy only if unable to tolerate BCG
Restaging TURBT


• 150 cases who underwent re-staging
  TURBT

     • Residual disease found in 76% Patients
     • Upstaging to muscle invasive disease in 30% of
       patients who initially had superficial disease
• Results are similar when same surgeon
  performs resection
Management


• cTis
  – Induction Immunotherapy
  – If response consider maintenance BCG
     • (x 3 years)
  – Recurrent or persistent CIS, consider
    cystectomy after no more then 2 courses of
    BCG
Impact of Progression
2nd Course of BCG

 Salvage up to 50% on
  non-responders
                                       # courses   Progression   %
                                                   Rate          Developing
 Risk of progression and                                        Mets
  Mets increases as the #                   1          7%           5%
  courses of BCG
  increases
                                            2         11%          14%

                                            3         30%          50%

Catalona et al., J Urol, 137: 220-4, 1987
Management


• cT2
  – Radical Cystectomy remains treatment of
    choice
  – If positive nodes on CT- Biopsy
  – Partial cystectomy in SELECTED pts:
     •   Solitary lesion (small)
     •   Amenable location to resection with margin
     •   No CIS
     •   Lymphadenectomy should always accompany
Management


– Cystectomy:
   • Positive margins tend to be lethal
   • Extended node dissection:
      – Common, internal, iliac, obturator nodes
– Urinary Diversion
   • NeobladdervsIlial Conduit
      – Patient preference, co-morbidities
      – Tumor characteristics
Role of Lymphadenectomy
Survival based on Number of LNs
(MSKCC N=637)




Node Negative     Node Positive Patients
Patients
SEER Database (N = 1923)




                           Konety et al, 2003
Extent of Dissection




 Overall Distribution   Single Positive Node
Management


– cT2
  • Radiation concomitant with chemo therapy
        –   No hydronephrosis
        –   Repeat TUR and boost to 65Gy if negative
        –   Simulate/treat patient with empty bladder
        –   High recurrence rate
  • Radiation alone in patients with extensive co-
    morbidities
Management


– cT3/T4
  • Strongly consider neoadjuvant chemotherapy
  • Radical Cystectomy
DSS 1.66 in favor of chemo (p=.002, Overall Survival 1.33 in favor of chemo p
Adjuvant Trials

Series     Chemo       N     Survival
Richards   5FU/Dox     129   No
Freiha     CMV         55    No
Studer     Cisplatin   77    No
Stockle    MVAC        49    Yes
Skinner    CAP         91    Yes
Neoadjuvant Chemotherapy plus Cystectomy and PLND
     Survival and Local Relapse analysis (N = 307)
     Dotan el al, ASCO 2005

Treatment                      5 year Survival   Freedom from local
                                                 relapse
Neoadjuvant MVAC + >10 nodes   81%               91%
Surgery alone >10 nodes        64%               90%
Neoadjuvant MVAC <10 nodes     55%               73%
Surgery alone < 10 nodes       39%               66%
No cystectomy                  11%               12%
Management


– Metastatic Disease
   • Gemcitabine/Cisplatin preferred
      – Equivalent efficacy to MVAC
   • 3 drug regimens have not been shown to be more
     efficacious
   • Carboplatin is NOT a substitute for Cisplatin
      – Consider split dose cisplatin for borderline renal function
   • Consider Carboplatin or Taxane-based regimens for
     patients not candidates for Cisplatin
Management


– Bladder cancer is a lifelong disease
– Attention to published surveillance protocols
– Attempt multi-disciplinary care whenever
  possible
– Do not forget about upper tracts

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W. Hassen - Bladder cancer - Guidelines

  • 1. Bladder Cancer Guidelines A Brief Review Waleed A. Hassen M.D. Chairman of Urology Tawam Hospital Assistant Professor Johns Hopkins Medical Institutions
  • 2. Estimated new cancer cases. 10 leading sites by gender, US, 2000 38 300 14 900
  • 3. Understanding Pathology WHO/ISUP 1998 Consensus WHO 2004 • Papilloma • Papillary urothelial neoplasm of low malignant potential (PUNLMP) • Urothelial Carcinoma low-grade • Urothelial Carcinoma high grade * – Previously classified grade 2 now high grade
  • 4. Understanding Pathology Recurrence vs Progression Pathology 5 yr Recurrence Prob. Muscle Invasion Ta, Low grade 50% Minimal Ta, high grade 60% Moderate T1, low grade 50% Moderate (rare) T1, high grade 50-70% Moderate-High Tis 50-90% High
  • 5. Understanding Pathology Pathologic Reporting • Pathology report must comment: – Histologic grade – The presence of muscularispropria, and degree of involvement – Presence or absence of LVI – Presence or absence of CIS
  • 7. Understanding Pathology Risk (NMIB) • Low risk – Initial Low grade, <3cm lesion • Intermediate – Low grade recurrent, multiple lesions, >3 cm • High – Any high grade or CIS
  • 8. Staging • Initial suspicion of TCC – Office cystoscopy – Cytology • Suspect NMIBC – Image upper tracts – Pelvic CT before TURBT – EUA – Mapping biopsies if indicated
  • 9. Staging • Suspect Muscle Invasive Disease – CBC, Chemistry including AlkPhos – CXR or CT Chest – Upper tract imaging – CT or MRI – Bone Scan if Alk. Phos elevated or symptoms
  • 10. Transurethral Resection • Goals of TUR: – Complete resection of all visible tumor when possible – Adequate mapping of bladder if needed – Adequate staging by ensuring presence of muscle
  • 11. Management • cTa (low grade) – Complete resection – Observation vs single dose intravesical chemotherapy*
  • 12. Management • cTa (high grade) – Complete resection – Re-resection if no muscle in specimen* – Induction Immunotherapy – Chemotherapy only if unable to tolerate BCG
  • 13. Management • cT1 (high grade) – Complete resection – Strongly advise re-resection – Consider early cystectomy especially if re- resection shows higher stage or volume disease – Induction BCG otherwise – Chemotherapy only if unable to tolerate BCG
  • 14. Restaging TURBT • 150 cases who underwent re-staging TURBT • Residual disease found in 76% Patients • Upstaging to muscle invasive disease in 30% of patients who initially had superficial disease • Results are similar when same surgeon performs resection
  • 15. Management • cTis – Induction Immunotherapy – If response consider maintenance BCG • (x 3 years) – Recurrent or persistent CIS, consider cystectomy after no more then 2 courses of BCG
  • 17. 2nd Course of BCG  Salvage up to 50% on non-responders # courses Progression % Rate Developing  Risk of progression and Mets Mets increases as the # 1 7% 5% courses of BCG increases 2 11% 14% 3 30% 50% Catalona et al., J Urol, 137: 220-4, 1987
  • 18. Management • cT2 – Radical Cystectomy remains treatment of choice – If positive nodes on CT- Biopsy – Partial cystectomy in SELECTED pts: • Solitary lesion (small) • Amenable location to resection with margin • No CIS • Lymphadenectomy should always accompany
  • 19. Management – Cystectomy: • Positive margins tend to be lethal • Extended node dissection: – Common, internal, iliac, obturator nodes – Urinary Diversion • NeobladdervsIlial Conduit – Patient preference, co-morbidities – Tumor characteristics
  • 21. Survival based on Number of LNs (MSKCC N=637) Node Negative Node Positive Patients Patients
  • 22. SEER Database (N = 1923) Konety et al, 2003
  • 23. Extent of Dissection Overall Distribution Single Positive Node
  • 24. Management – cT2 • Radiation concomitant with chemo therapy – No hydronephrosis – Repeat TUR and boost to 65Gy if negative – Simulate/treat patient with empty bladder – High recurrence rate • Radiation alone in patients with extensive co- morbidities
  • 25. Management – cT3/T4 • Strongly consider neoadjuvant chemotherapy • Radical Cystectomy
  • 26.
  • 27. DSS 1.66 in favor of chemo (p=.002, Overall Survival 1.33 in favor of chemo p
  • 28. Adjuvant Trials Series Chemo N Survival Richards 5FU/Dox 129 No Freiha CMV 55 No Studer Cisplatin 77 No Stockle MVAC 49 Yes Skinner CAP 91 Yes
  • 29. Neoadjuvant Chemotherapy plus Cystectomy and PLND Survival and Local Relapse analysis (N = 307) Dotan el al, ASCO 2005 Treatment 5 year Survival Freedom from local relapse Neoadjuvant MVAC + >10 nodes 81% 91% Surgery alone >10 nodes 64% 90% Neoadjuvant MVAC <10 nodes 55% 73% Surgery alone < 10 nodes 39% 66% No cystectomy 11% 12%
  • 30. Management – Metastatic Disease • Gemcitabine/Cisplatin preferred – Equivalent efficacy to MVAC • 3 drug regimens have not been shown to be more efficacious • Carboplatin is NOT a substitute for Cisplatin – Consider split dose cisplatin for borderline renal function • Consider Carboplatin or Taxane-based regimens for patients not candidates for Cisplatin
  • 31. Management – Bladder cancer is a lifelong disease – Attention to published surveillance protocols – Attempt multi-disciplinary care whenever possible – Do not forget about upper tracts