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Surgical Management of Bladder Cancer

Surgical Management of Bladder Cancer. Dr. Hemant B. Tongaonkar. Professor & Head, Genitourinary & Gynecologic Oncology Tata Memorial Hospital, Mumbai. Bladder Cancer Epidemiology. 1.5-2% of all malignant neoplasms in males in India

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Surgical Management of Bladder Cancer

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  1. Surgical Management of Bladder Cancer Dr. Hemant B. Tongaonkar Professor & Head, Genitourinary & Gynecologic Oncology Tata Memorial Hospital, Mumbai

  2. Bladder CancerEpidemiology • 1.5-2% of all malignant neoplasms in males in India • Second commonest urologic malignancy after prostate cancer • More common in industrialised than in developed countries • More common in urban than rural areas

  3. Bladder CancerInvestigations • Urine Cytology • Excretory Urography • Cystoscopy & Biopsy of tumour • Bimanual Examination • Ultrasonography • CT Scan Abdomen & Pelvis • Metastatic Work-up

  4. Bladder CancerStaging

  5. Superficial Bladder Cancer Treatment Transurethral resection of bladder tumours + Multiple random punch biopsies from bladder & prostatic urethra To identify high risk factors

  6. Low risk Observe High risk Aggressive treatment Prophylactic therapy Close monitoring Superficial Bladder CancerAim of Treatment Identify risk factors to predict natural history

  7. Random Mucosal BiopsiesIn Superficial Bladder Cancer • Rationale: To detect abnormalities (CIS, dysplasia or Ca) in normal looking areas in bladder & prostatic urethra (Althausen) • Abnormal biopsy predictive of recurrence &/or progression • Indication for intravesical therapy • Low risk 4-6% High risk 11.6% (EORTC 99) • Random biopsies often useless & add nothing to prognosis or treatment decision • Tumour implantation a possibility (Clemeny 2003) • Only indication: +ve cytology in presence of papillary tumours

  8. Sites for selected mucosal biopsies in TUR

  9. Superficial Bladder CancerProblems in Management • Local relapse after adequate TUR 70-80% • Progression to muscle invasion 20%

  10. Superficial Bladder CancerFactors Affecting Natural History • Tumour grade • Multiplicity & Tumour size • Condition of adjacent epithelium • Depth of invasion • Tumour configuration • DNA ploidy • Vascular & Lymphatic emboli • Biologic & Genetic factors

  11. SBC: Natural HistoryImpact of Tumour Grade • Strong correlation bet tumour grade & tumour stage: Low grade Superficial High grade Invasive • Grade I <5% invasive at diagnosis Grade III 50% invasive within 2 yrs • Strong predictor of survival Grade I 95% survive 5 years Grade III 40% survive 5 years

  12. SBC: Natural HistoryImpact of Lamina Propria Invasion • Marked diff in biologic behaviour of stage Ta & T1 tumours • T1: High risk of recurrence & progression Worst with T1G3 Progression rate % Ta T1 NBCCG-A Study 4% 24% BritishStudy 0% 46%

  13. Muscularis Mucosae • Often confused with muscularis propria • Proper labeling of tissue imp • Need for interpretation of the whole picture • Prognostic impact demonstrated T1a: Between epithelium & muscularis mucosae T1b: Level of muscularis mucosae T1c: Between muscularis mucosae & submucosa

  14. SBC: Natural HistoryImpact of T Size & Multiplicity • Larger or multiple tumours: Worse prognosis • With multiple tumours: Increased risk of recurrence Reduced interval to recurrence • With increasing tumour size: Increased risk of recurrence & progression < 5 cm 9% > 5 cm 35% progression rate

  15. SBC: Natural HistoryImpact of Mucosal Changes Strong predictor of local recurrence & stage progression Recrate % Normal Abnormal Althausen 3.8% 78% Heney 8.0% 33%

  16. Superficial Bladder CancerRisk Grouping • Low risk: Ta G1 Single <3 cm tumour with rec rate <1/ year Single post-op instillation of chemo • High risk: T1 G3 Multifocal Large Highly recurrent & Tis • Intermediate: All others TaT1 G1-2 >3 cm Single post-op instillation of chemo & to continue intravesical therapy in high & intermediate risk

  17. High risk of recurrence Chemotherapy Thiotepa Doxorubicin Epirubicin Mitomycin Ethoglucid High risk of progression Immunotherapy BCG Interferon Interleukin-2 KLH Superficial Bladder CancerIntravesical Therapy

  18. Superficial Bladder CancerIntravesical Chemo on Recurrence

  19. Superficial Bladder CancerIntravesical BCG on recurrence

  20. Superficial Bladder CancerIntravesical Chemo on Progression

  21. Superficial Bladder CancerIntravesical BCG on Progression • Reduces stage progression rate • Reduces progression to muscle invasion • Increases progression-free interval • Reduces no of patients requiring cystectomy • Increases period of bladder preservation • Reduces no of deaths from disease • Increases disease specific survival

  22. Superficial Bladder CancerIndications of Intravesical Therapy • Multiple or multicentric tumours • Rapidly recurrent tumours • Lamina propria invasion (T1) • Poorly differentiated tumours • Dysplasia or CIS in random biopsies

  23. Intravesical BCG vs Control TMH TRIAL DFS

  24. Multivariate Analysis of Prognostic Variables

  25. Carcinoma-in-situ of Bladder • Flat intraepithelial neoplasm of high histologic grade (Melicow 1952) • Exists in 2 forms Aggressive: Can dev into solid muscle invasive tumour Non-aggressive (Ca paradoxicum): Lacks capacity of invasion & mets (Weinstein) • Occurs rarely with low grade SBC 25% patients with high grade SBC 20-75% of high grade muscle-invasive Ca • 20% pts undergoing cystectomy for CIS have microscopic muscle invasive cancer

  26. CIS Bladder: Natural History • Not clearly understood Some have protracted course > 10 yrs without muscle invasion Others progress rapidly to muscle invasion & has poor prognosis despite definitive Rx • Symptomatic patients have shorter interval preceding muscle invasion • Diffuse vs. Focal: Prognostically diff entities • Risk of progression to muscle invasion: Focal CIS 8% Diffuse CIS 78% • High rec & progression rate despite standard definitive therapy: Poor prognosis

  27. Carcinoma-in-situ of BladderTreatment Options • Transurethral resection • Immediate cystectomy • Intravesical chemotherapy • Intravesical immunotherapy

  28. CIS Bladder: Management • TUR: High rec rate (80-100%), progression rate (50-80%) & mortality (30-40%) since: Lesion not visible endoscopically Ill-defined margins Too extensive to treat Ass with muscle invasion in many • Immediate cystectomy: Advocated since CIS ass with invasive tumour in majority 65-80% survival Results not diff if cystectomy done after failure of intravesical therapy

  29. CIS Bladder: Management • Intravesical chemo: CR rates 20-46% only irrespective of agent used: Suboptimal • Intravesical BCG immunotherapy: - Most appropriate first line therapy - Excellent results: 70-82% CR - BCG vs. Cystectomy: No difference - CIS after BCG failure: Ominous but cystectomy still possible - Long-term results unclear: Lifelong follow up essential

  30. Cystectomy for superficial disease1. Low- to moderate-grade polychronotropic disease that renders the bladder nonfunctional2. High-risk superficial disease that has not responded to early intravesical therapy. 3.Immediate cystectomy is an option in high- grade T1 disease, especially if the presentation is multifocal, but it is generally considered as a treatment option after assessing the response to a course intravesical therapy

  31. Muscle Invasive Bladder CancerOptions of Management • Radical Cystectomy • Radical Radiation Therapy • Chemotherapy • Combined Chemo + Radiation therapy in selected patients • Pre-op Radiotherapy + Surgery • Neoadjuvant Chemotherapy + Surgery

  32. Invasive Bladder CancerRadical Cystectomy • Treatment of choice : Gold Standard Local control 90-95% Survival 30-60% • 50% die of metastatic disease : Related to nodal mets & depth of invasion : Need for adjuvant / neoadjuvant therapy • Operative mortality low • Nerve sparing technique preserves potency • Requires urinary diversion in majority

  33. Muscle Invasive Bladder CancerRadical Cystectomy : Results (Herr, Urol Oncol 2, 92, 1996)

  34. Radical CystectomyDFS vs pStage & LN status

  35. Partial Cystectomy • Urachal adenocarcinoma at the dome • TCC bladder if: Solitary muscle invasive tumour Location at dome Preferably no extravesical spread Random mucosal biopsies negative • Need to perform ureteric reimplantation not an absolute contraindication Intra-op F.S. for –ve surgical margins mandatory

  36. Extraperitoneal Radical cystectomy

  37. Open Vs Laparoscopic approach Hand assisted approach

  38. Robotic Radical Cystectomy Da Vinci

  39. Prostate & SV sparing cystectomy • Rad cystectomy adversely affects male sexuality & QOL (Potency rates 13-25%) • Nerve sparing technique, 50% still lose potency (Walsh) • Prostate & SV sparing cystectomy developed • Functional results better but oncological outcome needs to be evaluated over a longer follow up

  40. Invasive Bladder CancerImpact of Lymphadenectomy • Valuable staging manouevre • Identifies high risk group requiring adjuvant therapy • Prognostication • Therapeutic in presence of micromets: Curative potential & survival benefit (Stein 2003, Skinner 1982, Madersbacher 2003, /vieweg 1999) Optimal boundaries need to be defined to accurately diagnose mets & to improve therapeutic benefit without increasing morbidity

  41. Muscle Invasive Bladder CancerPrognostic Factors • Tumour stage & LN status independent prognostic factors for DFS & OAS • Among node +ve patients, OC disease better survival than EV (Stein 2003, Herr 2002, Mills 2001, Vieweg 1999) • Substratification of nodal status imp for prognostication

  42. Bladder CancerNew insights into LN drainage • 290 patients RC+ Extended LND: LN +ve 27.9% • 15.8% located lat to ext iliac vessels • Isolated LN involvement in presacral or common iliac regions in 25% • Among pelvic LN +ve, 57% also had +ve nodes in common iliac & 31% above aortic bifurcation With standard LND, 74.1% +ve nodes would have been left behind & 6.8% mis-classified at LN -ve Leissner 2003

  43. Bladder CancerNew insights into LN drainage • Tumours localised to one half: 30% +ve nodes located on contralateral side (Leissner 2004) • Crossing lymphatic drainage in 41% of node +ve (Mills 2001) • Unpredictable, crossing drainage & skip lesions support more comprehensive LND

  44. Which aspects of LND contribute to improved results? • No of lymph nodes dissected, independent of no of +ve nodes • Extent of dissection: Standard vs Extended (Paulson 1998) Node -ve: Extended 90% vs 71% Standard Benefit regardless of the T stage (OC 85% vs 64%) Node +ve: 24% vs 7% • Herr (2003): RCT No LND (33%) vs Obturator (46%) vs Standard (60%)

  45. Non-invasive staging alternativesIdentification & localisation of nodes • Occult mets in grossly normal nodes common (approx 40%) • Despite modern imaging, incidence of occult mets 14-27% • CT /MRI fail to predict occult LN mets in 21-15% • PET scan: False –ve: 33% • Sentinel LN biopsy: Low accuracy Surgical excision with path evaluation only reliable method of staging bladder cancer

  46. Invasive Bladder CancerPre-op Radiation Therapy • Moderate dose 20 Gy / 5 Fr or 40-50 Gy / 20-25 Fr • Eradication of primary & nodal disease in few patients after pre-op RT alone • No survival benefit in randomised trials • Meta-analysis : 10% survival advantage • MD Anderson Trial : Reduces pelvic relapses in T3b patients (28% vs 9%) No survival benefit

  47. Invasive Bladder CancerRadical Radiation Therapy • Indications : Patients unfit / unwilling for surgery Rarely, selective modality Bladder conservation protocols • 55-65 Gy : Target volume definition & adequate margins important • Initial CR (T0) 40-52% Bladder DF 35-45% for T2-4 at 5 years Overall survival 25-40% Excellent local control means good survival • Salvage cystectomy for residual / rec disease • Cystitis, proctitis, sexual dysfn common

  48. Invasive Bladder CancerSalvage Cystectomy • Cystectomy following definitive radiation therapy • Planned procedure or for progressive, residual or recurrent disease after RT or for RT related complications • Survivals comparable to radical cystectomy in 4 randomised trials • Technical challenge: Devascularisation & fibrosis • Acceptable mortality & morbidity

  49. Invasive Bladder Cancer Ext Radiotherapy + Salvage Cystectomy Deferring cystectomy until local progression occurs does not adversely affect rate of metastases or compromise survival Imp implications for design of trials aimed at bladder conservation (4 randomised trials)

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