ECCLU 2011 - G. Thalmann - Localised invasive bladder cancer - Surgery

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  • Pathological stage tends to be higher and recurrence-free survival rates are lower in elderly patients
  • Datei: H. Herr SWOG 8710 Stammdatei:Zystektomie
  • Two consecutive series of 385 CCF patients and 394 Bern patients each with negative surgical margins on final pathology were analyzed. The Bern cohort was 5 years older than the CC cohort. Median follow up for CC cohort was 45 months and for Bern cohort was 59 months. No patient received any neoadjuvant therapy. Pathological characteristics, based on the 1997 Tumor-Nodes-Metastasis system and recurrence patterns were determined. Local progression was defined as any radiographic soft tissue density ≥ 2cm at or below the bifurcation of the aorta and systemic progrssin was defined as all other recurrences. Patients who had local progression concomitant with systemic were allocated to the systemic group.
  • Results: This table demonstrates that the incidence of positive nodes was higher with extended PLND for comparable pT stages: 16% v’s 7.5% for pT2 disease and 34% v’s 21% for pT3 disease.
  • Looking at the entire cohort, we see that with an extended PLND their the 5 year RFS is 59%, 14 % higher than the 45% 5yr RFS at CC.
  • So regardless of nodal status but for the same pTstage, we see only a slight difference between the pT2 stages of each institution, 63% at CC and 71% at Bern. Since the incidence for positive nodes in this patient population is approximately 15%, the difference of 8% in RFS between the institutions is appropriate. In patients more likely to harbnor postive nodes, the difference in survival is strinking, 19% at CC v‘s 49% at Bern. This is strongly in nfavor of an extended dissection.
  • The RFS by pTstage for node negative patients only. What we see here is that understaging by the limited PLND has left the node negative group contaminated with undetected positive LN thereby compromising the outcome of this subgroup
  • Under staging with a limited PLND has also left the LN-positive group with patients more more likely to harbor additional positive nodes which were not removed. As a result also compromising the outcome of this subgroup.
  • The variables with significant impact on RFS in the univariate analyses were tested in a multivariate analysis. Only ECE was an independent predictor for RFS with a more than doubled risk of recurrence for patients with ECE of lymph node metastasis compared to those without such extension. Tumor stage, number of positive lymph nodes and percentage of positive nodes are no independent predictors of RFS.
  • Abgebildet die Gesamtüberlebenskurve unserer 507 Patienten bis 10 Jahre nach Zystektomie. Tumorspezifisches Ueberleben innerhalb von 3 Jahren von 70%, im weiteren nehmen die Comorbiditäten an Wichtigkeit zu.
  • 5 Jahre nach Zystektomie lebten in unsere Serie noch 62% der Patienten, nach 10 Jahren immer noch 40% der Patienten. Wie sieht das Gesamtüberleben differenziert nach Tumorstadium, unabhängig vom Lymphknotenstatus aus?
  • Die gelbe Kurve repräsentiert Patienten mit organbegrenzten Tumoren und negativem Lymphknotenstatus. Hier liegt die 5J Ueberlebensrate 73%. Die blaue Kurve repräsentiert Patienten mit organüberschreitenenden Tumoren und negativem Lymphknotenstatus. Hier liegt die 5J Ueberlebensrate bei 50%. Die violette Kurve repräsentiert Patienten aller Tumorstadien mit pos. Lymphknotenbefall. Hier liegt die 5J. Ueberlebensrate immerhin noch bei beachtlichen 25%. Wie sehen die Resultate betreffend Lokalrezidive und Fernmetastasierung aus?
  • Stammdatei: Zystektomie Datei: Nerve sparing cystectomy Bern
  • Stammdatei: Zystektomie Datei: Nerve sparing cystectomy Bern
  • Poehler Helmut 9. 12. 1931 19. 3. 1992 Surg. ..... Bl Ca Austr. 94
  • ECCLU 2011 - G. Thalmann - Localised invasive bladder cancer - Surgery

    1. 1. Localised invasive bladder cancer: Surgery George Thalmann Department of Urology University of Bern Switzerland
    2. 2. “ It is important to preface this discussion with the reality of the disease: high-grade invasive bladder cancer is a lethal disease and any short cuts/mistakes in the treatment can be lethal to the patient” Richard Hautmann
    3. 3. TNM Classification Bladder Muscle Mucosa Lamina propria Tis (Carcinoma in situ) Ta (urothelium) T1 (Lamina propria) T2a (superficial muscle) T2b (deep muscle) T4 (perivesical organs) T3b (perivesical fat -macro) T3a (perivesical fat -micro) Ta, T1, Tis Non muscle invasive bladder cancer T2a to T4 Muscle invasive bladder cancer
    4. 4. Staging Chest x-ray Uro-CT scan abdomen/pelvis Bone scan IVU when Uro-CT not possible
    5. 5. Staging
    6. 6. Staging LIMITATIONS OF IMAGING CT / MRI: under-/overstaging in ~30% false neg. rate 68% for LNs, 16% false pos. (Herr HW. J Urol 1996; 47: 785-791) PET: Limited role (urinary excretion of tracer) Lymph node staging accuracy ~80%
    7. 7. Staging Cystoscopy Tumor biopsy Bimanual palpation Paracollicular biopsies Bladder wash cytology
    8. 8. Clark PE, et al. ,Cancer: 104:36, 2005. Radical Cystectomy Gold Standard in the therapy of muscle-invasive bladder cancer Indication: Invasive bladder cancer N0 M0 Patient operable Elderly patients not to be excluded
    9. 9. Pelvic Lymph Node Dissection
    10. 10. Bladder Cancer Outcomes by Surgical and Pathologic Variables for the 268 Patients Undergoing Cystectomy SWOG 8710 H.W. Herr et al., J Clin Oncol 22:2781-2789, 2004 Survival Local Recurrence Variable At Risk Deaths 5-Year Survival (%) P No. of Pts. % P PLND None Limited Standard 24 98 146 17 63 79 33 46 60 .01 12 22 7 50 22 5 <.0001 Surgeon Urologist Urologic oncologist 153 115 98 61 48 58 .053 33 8 23 6 .06 Institution type Academic Community VA/military 137 84 47 72 52 35 57 54 40 .053 14 18 9 10 21 19 .02 Urinary diversion Ileal Conduit Continent stoma or orthotopic 191 77 126 33 48 63 .006 29 12 15 16 .93
    11. 11. Hautmann RE et al., J Urol 2006; 176: 486-92 Pelvic Lymph Node Dissection
    12. 12. 2 3 1 1 external iliac 3 internal iliac 2 obturator fossa Template of extended lymph node dissection Pelvic Lymph Node Dissection
    13. 13. LIMITED PLND: CC EXTENDED PLND: Bern Boundaries of Dissection {median 12 nodes: range 2-31} {median 22 nodes: range 10-43} Dhar N. et al., J. Urol 179: 873-878, 2008
    14. 14. Patients with pT2 and pT3 pN0 bladder cancer <ul><li>2 consecutive series: </li></ul><ul><li> CC 385 pts : median age 62 (31-84) Bern 394 pts : median age 67 (35-89) </li></ul><ul><li>Follow-up: </li></ul><ul><li> CC : median 45 months (1.1-166) </li></ul><ul><li> Bern : median 59 months (1.3-229) </li></ul><ul><li>No neoadjuvant radiotherapy/chemotherapy </li></ul><ul><li>1997 TNM system </li></ul>Dhar N. et al., J. Urol 179: 873-878, 2008
    15. 15. Results: Number of Pathological Positive Nodes Dhar N. et al., J. Urol 179: 873-878, 2008 Institution Stage # of Patients # with pN+ CC Limited pT 2 pN 0-2 200 15/200 (7.5%) Bern Extended pT 2 pN 0-2 150 24/150 (16%) CC Limited pT 3 pN 0-2 136 29/136 (21%) Bern Extended pT 3 pN 0-2 172 59/172 (34%)
    16. 16. RFS pT2&3 , pN 0-2 p< 0.001 Limited PLND Extended PLND Dhar N. et al., J. Urol 179: 873-878, 2008
    17. 17. RFS: pT2 pN 0-2 & pT3 pN 0-2 p< 0.001 Limited PLND Extended PLND Dhar N. et al., J. Urol 179: 873-878, 2008
    18. 18. RFS: pT2 pN 0 & pT3 pN 0 p< 0.001 Limited PLND Extended PLND Dhar N. et al., J. Urol 179: 873-878, 2008
    19. 19. RFS: pT2&3 pN + p< 0.001 Limited PLND Extended PLND Dhar N. et al., J. Urol 179: 873-878, 2008
    20. 20. Prognosticators of outcome <ul><li>pN1 vs pN2 Vieweg et al. J Urol 1999 </li></ul><ul><li> Herr et al. J Urol 2003 </li></ul><ul><li>Number pos. LN Lerner et al. J Urol 1993 </li></ul><ul><li> Stein et al. JCO 2001 </li></ul><ul><li>Ratio +LN/ tot LN Stein et al. J Urol 2003 </li></ul><ul><li> Herr et al. J Urol 2003 </li></ul><ul><li>Extracapsular Mills et al. J Urol 2001 </li></ul><ul><li>extension </li></ul>
    21. 21. LNM LC LC Extracapsular extension of lymph node metastasis
    22. 22. Multivariate analysis for recurrence-free survival N = 101 Patients Variables p Value Hazard ratio 95% CI extracapsular extension or not 0.019 2.11 1.12 - 3.96 tumor stage 0.16 1.70 0.79 - 3.66  5 vs. <5 pos. nodes 0.43 1.36 0.62 - 3.00  20% vs. <20% pos. nodes 0.43 1.34 0.63 - 2.88
    23. 23. Overall survival of the entire cohort (n=507) Madersbacher S. et al., Journal of Clinical Oncology; 21(4):690-6, 2003 100 75 50 25 0 0 5 10 n = 507 probability of overall survival % years from cystectomy
    24. 24. Madersbacher S. et al., Journal of Clinical Oncology; 21(4):690-6, 2003 Overall survival of the entire cohort (n=507) 100 75 50 25 0 0 5 10 n = 507 probability of overall survival % years from cystectomy
    25. 25. Overall survival stratified according to tumor stage in lymph node negative patients Madersbacher S. et al., Journal of Clinical Oncology; 21(4):690-6, 2003 pT3pN0 (n = 120) pT1pN0 (n = 75) pT4pN0 (n = 46) pT2pN0 (n = 125) 100 75 50 25 0 Overall survival % 5 10 years from cystectomy 0
    26. 26. Recurrence-free survival in organ-confined, non organ confined and lymph node positive patients Madersbacher S. et al., Journal of Clinical Oncology; 21(4):690-6, 2003 pT1-4 pN+, n = 124 pT1-2 pN0, n = 217 pT3-4 pN0, n = 166 years from cystectomy 0 5 10 100 75 50 25 0 probability of recurrence free survival [%]
    27. 27. Madersbacher S. et al., J Clin Oncol; 21(4):690-6, 2003 Hautmann RE et al, J Urol; 176: 486-492, 2006 Stein JP et al., J Clin Oncol; 1;19(3):666-75, 2001. Radical Cystectomy Results of large series: Bern: 5 y recurrence-free survival all (4% pTa/pTis) 62% Ulm: 5 y recurrence-free survival all 59% UCLA: 5 y recurrence-free survival all (20% pTa/pTis) 68% Bern: 5 y recurrence-free survival organ-confined, LN- 73% Ulm: 5 y recurrence-free survival organ-confined, LN- 53-82% Bern: Local recurrence-free survival all 92% Ulm: Local recurrence-free survival all 96/84% Bern: Local recurrence-free survival organ-confined 97% Ulm: Local recurrence-free survival organ-confined 96%
    28. 28. Radical Cystectomy Results of large series: Positive LNs average ~25% Long term survival 20-30% Bern: 80% of all recurrences were attributable to distant metastases and 64% of LN+ progressed. Madersbacher S. et al., J Clin Oncol; 21(4):690-6, 2003 Fleischmann A et al., J Clin Oncol, 23(10):2358-65, 2005 Hautmann RE et al, J Urol; 176: 486-492, 2006 Stein JP et al., J Clin Oncol; 1;19(3):666-75, 2001.
    29. 29. Local recurrence and distal failure in pN+ bladder cancer patients after radical cystectomy n patients with pN+ 124 local recurrence only 16 (13%) distant recurrence 64 (51%) NED 44 (36%) Radical Cystectomy Good local control: improvement of survival depends on reducing distant (micro)metastases.
    30. 30. Bochner Prognosticators of outcome Internat. Bladder Cancer Nomogram Consortium; JCO 24:3967-3972.
    31. 31. Prognosticators of outcome JCO 24:3967-3972.
    32. 32. Timing of Cystectomy Patients treated within 3 months: Better RFS, DSS and OS TNM status similar, more vascular invasion in group > 3 months (Hara I et al., Jpn J Clin Oncol 2002; 32: 14-18) Treatment delay > 12 weeks: OS: 62% vs 35% (p=0.05, HR 1.93 CI 0.99-3.76) Extravesical or LN+: 84% vs 42% (Sanchez-Ortiz RF et al., J Urol 2003, 169: 110-115) Treatment > 90 days: pT3 81 vs 52% (Chang SS et al., J Urol 2003; 170: 1085-7)
    33. 33. Mortality rate 1-2% Overall early complication rate 25 - 30% Blood transfusions 30 - 50% (preoperative anemia) Radical Cystectomy Gold Standard in the therapy of muscle-invasive bladder cancer Indication: Invasive bladder cancer N0 M0 Patient operable Elderly patients not to be excluded
    34. 34. Complications of cystectomy Mortality 1 – 2% in major centers Morbidity How to prevent Cardiovascular preop work – up, monitor blood (stroke, MI) pressure Pulmonary embolism low molecular heparin started on the eve of surgery, stockings, mobilisation, bipolar coagulation Ileus Prostigmine, Metoclopramide
    35. 35. Morbidity (cont.d) How to prevent Lymphoceles ligatures distally, drainage Pyelonephritis, Remove stents on day 5-7, Septicemia, atraumatic surgery, preserve Urinary fistulas ureter vasculature, no traction on anastomosis Metabolic acidosis N a -bicarbonate Complications of cystectomy Mortality 1 – 2% in major centers
    36. 39. 100 60 80 40 0 20 time from operation (years) % continent < 65 years (n=161) > 65 years (n=170) p=0.005 Nighttime continence according to age at the time of operation 1 2 5 3 4 Kessler et al., J Urol, 172, 1323, 2004
    37. 40. 100 60 80 40 0 20 0 1 2 5 time from operation (years) % continent Nighttime continence according to attempted neurovascular bundle preservation 3 4 with attempted nerve sparing (n=256) without attempted nerve sparing (n=75) p=0.036 Kessler et al., J Urol, 172, 1323, 2004
    38. 41. 100 60 80 40 0 20 0 1 2 time from operation (years) % recovery rate of erectile function Kessler et al., J Urol, 172, 1323, 2004 with attempted bilateral nerve sparing (n=38) with attempted unilateral nerve sparing (n=218) p<0.0001 Reported recovery of erectile function (no versus reduced or normal erections) according to attempted sparing of one, both or neither neurovascular bundles without attempted nerve sparing (n=75)
    39. 42. Simone G et al., UROLOGY 72: 162–166, 2008. Prostatic Capsule and Seminal Vesicle-Sparing Cystectomy: Improved Functional Results, Inferior Oncologic Outcome All disease progressions occurred in patients with Stage T2G3 tumor at TURB. Patient age 57 y (range 39 - 66) Local recurrence rate 20% at 2 y FU Distant failure rate 30% at 2 y FU 1-year cancer-specific mortality rate 10% 2-year 20%
    40. 43. Ong CH et al., J Urol 183, 1337–1342, 2010 Individualized Seminal Vesicle Sparing Cystoprostatectomy Combined With Ileal Orthotopic Bladder Substitution Achieves Good Functional Results N = 31 100% continent 74% potent preoperatively 17(55%) Unilateral SVS RC 14(45%) Bilateral SVS RC pTa/pT1 15 (48%) pT2 9 (29%) pT3 2 (7%) pT2-3 pN1 5 (16%) No pos. SM Median Follow up 18 months (range 3 – 63)
    41. 44. Ong CH et al., J Urol 183, 1337–1342, 2010 Individualized Seminal Vesicle Sparing Cystoprostatectomy Combined With Ileal Orthotopic Bladder Substitution Achieves Good Functional Results N = 31 100% continent 74% potent preoperatively 17(55%) Unilateral SVS RC 14(45%) Bilateral SVS RC Daytime continence 27/29 (93%) Nighttime continence 19/29 (66%) Remained potent 5/19 (79%) Pelvic recurrence 1 (3%) Distant recurrence 4 (13%) Median Follow up 18 months (range 3 – 63) The preliminary results on continence and oncological outcomes are at least as good as those of conventional RC.
    42. 45. Laparoscopic Cystectomy? „ We believe that nerve-sparing LRC may be the treatment of choice in well- selected younger patients with low-volume, organ-confined disease in whom preservation of sexual function is a high priority. Nerve-sparing LRC is a technique in evolution that is an option at centers competent in advanced urologic laparoscopy .“ UROLOGY 68: 778–783, 2006. N = 5
    43. 46. Robotic-assisted Cystectomy? „ Robot-assisted laparoscopic radical cystoprostatectomy with intracorporeal ileal neobladder construction is technically feasible . However, its role in the management of invasive bladder cancer remains to be defined .“ Sala LG et al. J Endourol 20: 233–5, 2006.
    44. 47. Conclusions <ul><li>Extended pelvic lymph node dissection provides a clear survival advantage </li></ul><ul><li>Open radical cystectomy is the gold standard in the treatment of localized muscle invasive bladder cancer </li></ul>
    45. 48. ?
    46. 50. Staging Surface Frequency
    47. 51. <ul><li>EAU Guidelines </li></ul><ul><li>4 Treatment options : </li></ul><ul><li>Ileal conduit </li></ul><ul><li>Bladder reconstruction </li></ul><ul><li>Continent pouch </li></ul><ul><li>Ureterosigmoidostomy </li></ul><ul><li>(„Minimal“ urinary diversion) </li></ul>Diversion?

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