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Invasive & metastatic bladder cancer

Invasive & metastatic bladder cancer. By Dr.Turky Al- Mouhissen R4 Urology Resident KKNGH. Outline:. Clinical presentation and evaluation Axial imaging Radical cystectomy for invasive bladder Ca. Adjuncts to standard surgical therapy Alternative to standard therapy

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Invasive & metastatic bladder cancer

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  1. Invasive & metastatic bladder cancer By Dr.Turky Al-Mouhissen R4 Urology Resident KKNGH

  2. Outline: • Clinical presentation and evaluation • Axial imaging • Radical cystectomy for invasive bladder Ca. • Adjuncts to standard surgical therapy • Alternative to standard therapy • Management of metastatic bladder Ca. • Local salvage & palliative therapy

  3. Clinical presentation, Diagnosis & evaluation • Presentation: • hematurea (Gross / microscopic) 80% • Irritative voiding symptoms • Constitutional symptoms • Metastatic symptoms

  4. TUR: • Defines detrusor invasion • Once histological diagnosis of invasion made, noninvasive imaging may provide extent of tumor • Pt with suspected invasive lesion before TUR, axial imaging should be performed prior to resection

  5. Bimanual examination: • Sensitive & inexpensive for evidence of extravesical extension • Usually under anesthesia • Bimanual palpation of bladder before & after resection has been correlated with stage of lesion • Wijkstrom & colleages (1998) suggested that presence of palpable mass after TUR correlates significantly with stage T3 and prognosis after treatment

  6. Restaging TUR: • Reduction of stage to p(O) by a 2nd TUR associated with favorable long term survival in selected pts (Herr, 1999) • Other Authors disagreed (Thrasher et al, 1994) • Recommended when definitive muscle invasion has been identified + the pt is candidate for alternative s to standard surgical intervention

  7. Axial imaging • CT: • Most commonly employed for staging • Tends to understage advanced disease • Like other imaging technique, can`t identify microscopic extravesical extension • Correlation of CT findings with pathologic findings of cystectomy is 65-80% (kellett et al, 1980) • CT detects metstatic disease in regional LN in 50-85%

  8. MRI • Ideal for pts with renal insufficiency or contrast allergy • Failure to detect microscopic nodal disease with MRI is similar to that with CT (tavaras and Haricak, 1990; Jagar et al, 1996) • Understaging & overstaging remain persistent problems with both CT & MRI, occurs in about 30% (buy et al, 1988; kim et al, 1994)

  9. Bone scan: • Several studies 1980-1990 support the impression that preop. Bone scan is not necessary for pts with clinically organ confined muscle invasive bladder Ca. • Pts who have signs & symptoms of bone mets, bone scan is suggested

  10. Braendengen & colleages (1996) retrospectively evaluated 337 pts with T2 or higher treated in Norway 1980-1990. • Half of them had precystectomy bone scan, and 41% developed bone mets after surgical treatment • These investigators noted that ALP levels didn`t provide additional information regard to bone mets • They recommended that abnormal Bone scan to be correlated with MRI to increase diagnostic accuracy (Davey at al, 1985)

  11. Positron Emission Tomography: • PET scan is based on the uptake of flurodeoxyglucose by tumor cells • Success in identifying malignant lymphadenopathy has been greater than that in staging bladder lesions • Reason is that the [flurodeoxyglucose tracer] in urine obscures details adjacent to bladder lumen ( can be partially overcomed by continuous irrigation duriing the study)

  12. Laparoscopic Staging: • Caution has been advised by those who have noted a significant incidence of port site recurrence in pts with bladder Ca. undergoing lap. Pelvic node dissection compared with comparable group of pts with prostate Ca. (Elbahnasy et al 1998) • Larger studies required especially with the advance of techniques facilitating completely intracorporeal lap. / Robotic assisted cystectomy

  13. Radical Cystectomy • The standard surgical approaches to muscle invasive nonmetastatic bladder TCC is Radical cystoprostatectomyinmale & anterior exenterationin female + en bloc pelvic lymphadenectomy • Metastatic bladder Ca. or pts with significant comorbidities alternative approaches • pts with local symptoms might be candidate for palliative cystectomy

  14. Efficacy of cystectomy % Disease-Specific Survival by Pathologic Stage after Radical Cystectomy with & without Pelvic Lymph Node Metastasis: Selected Series (1980-1999)

  15. Surgical points in cystectomy • B/L pelvic lymphadenectomy • In male: • prostate & bladder en bloc • +/- nerve sparing, +/- urethrectomy • In female: • anterior exenteration requires removal of uterus, fallopian tubes, ovarries, bladder, and a segment of anterior vaginal wall • +/- urethra sparing, +/- vaginal preserving

  16. Nerve-Sparing Approach in male: • Usually feasible to preserve the neurovascular bundles during cystectomy As TCC doesn`t frequently extend beyond prostate • Unless the primary bladder Ca. is extensive • If any question regarding tumor involvement, wide excision of the neurovascular bundle on the ipsilateral side of tumor is done

  17. Vagina-Preserving Approach: • In the past, both ovaries & much of vagina were often excised with no potential of sexual function • In younger pts, it `s possible to leave one ovary and to reconstruct the vagina • Sexual function can be maintained • Majority of surgical candidates, urethral, vaginal, and cervical involvement is unusual except • Pts with extremely large tumors • Tumors involving bladder neck • Diffuse CIS • Locally / regionally advanced tumors (Schoenberg et al, 1999)

  18. Male urethra: • The incidence of urethral recurrence has been documented 4%- 18% (Darson et al, 2000) ( 7.9% reported by Skinner & Colleages) • Prostatic urethral involvement by Ca. is the most significant factor in anterior urethra recurrence • Estimated 5 year probability of urethral recurrence • 5 % without any prostatic involvement • 12 % with superficial prostate involvement • 18 % with deep prostate involvement (stein et al, 2005)

  19. CIS of bladder neck & trigone was also significantly associated with prostatic urethra involvement in this study (wood et al, 1989) • Some reported the significance of prostatic stromal invasion in ant. Urethral recurrence • 64 % those with stromal invasion • 25 % with prostatic ducts • 0 % with prostatic urethral urethelium (hardeman and Solowa, 1990; levinson et al, 1990)

  20. Other reported less incidence (Skinner & Colleages 1998) • 21% with prostatic stromal invasion • 15% with prostatic urethra or ductal involvement • Male pts undergoing cutaneous diversion should go simultaneous / delayed urethrectomy if • CIS prostatic urethra • Gross tumor prostatic urethra • In orthotopic diversion with residual urethra, should be done after frozen section documenting tumor free distal urethral margin (Lebret et al, 1998)

  21. Female urethra: • Mapping studies showed 2-12 % of female pts undergoing cystectomy for cure have urethral involvement (De Paepe et al, 1990) • Stein & colleages (1998) performed prospective path. Evaluation of 17 female cystec. Specimens removed for 1ry TCC • Tumors of bladder neck and urethra found in 19% & 7% respec. • Bladder neck involvement was found to be the most significant risk for tumor involvement of the urethra

  22. Intraoperative frozen-section of the proximal urethra is the best way to determine whether a female pt is a suitable candidate for orthotopic reconstruction (Darson et al, 2000) • Pts with : • Overt Ca. at bladder neck & urethra • Diffuse CIS • +ve margin Are poor candidates for orthotopic diversion, and should go immediate en bloc urethrectomy as part of cystectomy

  23. Ureteral Frozen-Section Analysis: • Ureteral Frozen-Section Analysis at time of cystectomy before anastomsis is standard practice • Urologists historically resected +ve margins to effect clearance of all documented ca. assuming better long term local disease control • Retrospective studies failed to demonstrate long term benefit (Linker & Whitmore et al, 1975; Johnson & Bracken 1977; Schoenberg et al, 1996) These studies were small, single institution retrospective experiences

  24. Role of lymphadenectomy: • Provides insight into the local extent of disease • Pts with limited tumor burden, have improved long term survival in absence of additional intervention (Skinner, 1982; Skinner & Lieskovsky, 1984; Lerner et al, 1993; Viewed et al, 1994, 1999; Schoenberg et al, 1996) • Risk of pelvic L.N. mets. Increases with tumor stage • pT2disease have 10-30% risk of +ve L.N. at time of surgery • pT3 & higher have 30-65% risk • Obturator & external iliac L.N. are the most common nodes involved by mets

  25. L.N. dissection done before/after cystectomy • The standard dissection: • Lateral limit is genitofemoral nerve • Medial limit is bladder • Cephalad limit is bifurcation of the common iliac art. • Caudal limit is endopelvic fascia • Obturaorfossa nodes included during dissection medially • Care to avoid accessory obturator vein, frequently present • The node of Cloquet is mobilized at the junction of the femoral canal and should be included

  26. Extended lymphadenectomy • shown to improve survival in pts with both L.N. –v & limited L.N. metastatic disease (Herr et al, 2002) • Includes tissues along the common iliac up to the bifurcation of aorta (distal paraaortic & paracaval) + includes presacral nodes • % of pts with node +ve disease who are identified are similar between standard V.s. Extended lymphadenectomy (bochner et al, 2004)

  27. L.N. yield is > 3 fold when dissecting and submitting separate L.N. pockets compared with en bloc (bochner et al, 2001) • Among pt with L.N. +ve, total no. of nodes removed at time of surgery affects prognosis • Pts with < or = 15 nodes removed had 25% 10-year recurrence-free survival & when > 15 removed, 36 RFS • 10 year RFS was significantly higher when pts had 8 or fewer L.N. +ve compared to more than 8 L.N. +ve (40% V.s 10%) (stien et al, 2003)

  28. Complications of radical cystectomy: • Mortality rate 1-2% • Complication rate 25% Morbidity 2ry to • Preexisting or comorbid conditions • Related to removal of bladder and adjacent structures • Related to use of bowel segment • Immediate / Early/ Late

  29. F/U after Radical Cystectomy: • Long term surveillance for • Tumor recurrence • Complications related to use of intestinal segment • Frequency of F/U controversial • Slaton & colleages (1999) did a retrospective review • Annual screening with physical exam, chemistry, CXR for pT1 • Semiannual for pT2 • Quarterly for pT3 + semiannual CT • Upper tract imaging after cystectomy is useful to exclude ureteralstenosis or upper tract tumor

  30. Adjuncts to standard surgical therapy Preoperative Radiation Therapy: Available randomized data suggests that for pts with pT3, preoperative Radiation Therapy • May improve local control • No survival advantage (Blackard, 1972; Ghoniem et al, 1985; smith et al, 1997) • Other nonrandomized trials supported that it doesn`t improve survival (Cole et al, 1995; Pollack et al, 1997)

  31. Neoadjuvant chemotherapy: • Allows potential downstaging in inoperable tumors • Treatment of micromets. When pt is not debilitated by a surgical procedure • Potential disadvantage is delay in delivery of definitive local therapy

  32. The Nordic 1 Trial Group used neoadjuvant chemo + low dose radio + cystectomy • 5 year OS was 59% in chemo group V.s. 51% in control (p= .1) • No difference observed for T1 & T2 • 15% improved survival for pts with T3-T4a who received neoadjuvant chemo. (p=.03) • 2 comprehensive meta-analysis of RCT also concluded • Neoadjuvantcisplatin based combination chemo. May offer improvement in OS. Of 5-6% among pts with locally advanced disease (Advanced Bladder Cancer Meta-analysis Collaboration, 2003; Winquist et al , 2004)

  33. Perioperative Chemotherapy: • M.D. Anderson Hospital evaluated 100 pts randomized either to 2 cycles of MVAC before & 3 cycles after cystectomy • At 32 months, no difference in survival was identified between 2 groups • A trend toward downstaging of larger lesion was noted in perioperative chemo. Group (Logothetis et al, 1998)

  34. Adjuvant Chemotherpy: • Pts with pathologicaly staged tumors with evidence of mets. may benefit from systemic therapy that could reduce • local recurrence or • distant metastatic relapse • Disadvantages • Difficult to assess tumor response to chemo in absence of radiological residual disease • Interference of post. Op. complications • Delay of administration of systemic therapy in proven mets

  35. The reports suggests that for pts with locoregional disease & pelvic L.N. involvement, Cisplatin based adjuvant therapy may provide survival advantage worth discussing with selected pts • there is no evidence to suggest administration of adjuvant chemo. To pts with T1-T2

  36. Alternatives to standard therapy • Radiation Therapy: • No randomized trials performed comparing radiation alone with cystectomy • Conventional Ext. Beam Rx control locally invasive tumors in 30-50% (Walace & bloom, 1976; Hyter et al 1999) • To improve rate of success, hyperfractionation schedules used • Randomized trials of hyperfractionation suggests that it may be useful in the future (larger controlled trials needed)

  37. TUR & partial cystectomy: • Some groups reported good local & distant control in small, low stage T2 treated with Radical TUR or partial cystectomy (Henry et al, 1988; Solsona et al, 1998;Roosen et al , 1997) • Solsona & colleages (1998) reported 5 year disease specific survival (similar to radical cystectomy !! ) with pts with –ve tumor bed and normal peripheral biopsy post Radical TUR • Non randomized

  38. Combined TUR / partial cystectomy + chemo: • Complete TUR alone for moderate to large T2 is unlikely (Kolozsy , 1991) • To augment conservative intervention, chemo. was added by some (Herr & scher, 1998; Sternberg et al 1999) • Hall & colleages (1984) described 61 pt treated with TUR + chemo. for T2 • 48 were free of muscle invasion on 1st surveillance cystosopy after initial complete TUR • 5 year disease specific survival was 75% compared with 25% those with residual or recurrent disease • Chemo. Shown to improve survival in pts downstaged to P0 at time of surgery (Herr, 1994) • Prospective randomized trials still needed

  39. Partial cystectomy: • Ideal pt for partial cystectomy: • Normally functioning bladder with good capacity • 1st time tumor recurrence with solitary tumor • Located in area allows 1-2 cm margin of resection • Only 5.8-18% of pts with muscle invasive bladder Ca. are suitable for partial cystectomy(Sweeny et al, 1992) • Survival rates ranges 25-55% in retrospective studies • Can reach up to 58% in well selected pts (Brananet al, 1978) • Rate of local recurrence 40-78% (Lindahal et al, 1984)

  40. Pelvic L.N. dissection + complete pathological staging of tumor should be done in partial cystectomy • Other indications of partial cystectomy: • Urachaladeno. • Primary pheochromocytoma of bladder • Osteosarcoma of bladder • Tumor within diverticulum

  41. Absolute contraindications of partial cystectomy : • CIS in bladder • Multifocal tumor • Relative contraindications: • High grade tumors • Located in trigone or bladder neck • Tumor that would require ureteralreimplnat. • As local recurrence is high ( 40-79% ) • Pt . post partial cystectomy needs cystoscopy + cytology Q 3/12 for the 1st 2 years, + regular CT abd. & pelvis

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