Surgical Management of Urothelial Carcinoma A 21 st Century Approach Douglas S. Scherr, M.D....
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Transcript of Surgical Management of Urothelial Carcinoma A 21 st Century Approach Douglas S. Scherr, M.D....
Surgical Management of Urothelial Carcinoma
A 21st Century ApproachDouglas S. Scherr, M.D.
Clinical Director, Urologic OncologyWeill Medical College of Cornell
University
Epidemiology
• 5th most common cancer in men
• 12,000 cancer related deaths/year
• 70% present as superficial TCC
• “Superficial” = Ta, Tis, T1
• Men>Women
Epidemiology
• 2.8% lifetime risk in caucasian men0.9% lifetime risk in African American men
• 1% risk in caucasian women0.6% African American women
• Carcinogens implicated in bladder cancer – could have 40 year latency period
Risk Factors for Transitional Cell Carcinoma
• Cigarette smoking: 2-4 fold increase risk4-AminobiphenylO-toluidine
• Arylamine exposure2-NaphthylamineBenzidine4-Aminobiphenyl
• Chemotherapy – cyclophosphamide
• Pelvic radiation therapy
Overview
• Role of TUR
• Neoadjuvant Chemotherapy
• Surgical Principles of Importance
• Minimally Invasive Techniques-Robotics-Prostate Sparing Techniques
• Future Horizons
TUR vs. TUR + BCGT1, GIII
• 153 patients (92 TUR+BCG, 61 TUR alone) 23% in BCG arm had co-existing CIS compared with 10% in TUR alone arm (p=0.04)
• 5.3 year median follow up
• Recurrence rate:a.) BCG: 70%b.) TUR alone: 75%
• Time to recurrence:a.) BCG: 38 months
b.) TUR alone: 22 months
• Progression Rate:
a.) BCG: 33%b.) TUR alone: 36%
• Cystectomy Requirement:a.) BCG: 29%b.) TUR alone: 31%
• Overall Survival: No significant difference
Shahin et al. J Urol 169: 96-100, 2003
Overall Survival Time to cystectomy
Recurrence Free SurvivalProgression Free Survival
Shahin et al. J Urol 169: 96-100, 2003
Neoadjuvant Chemotherapy Meta-Analysis
• Analysis of data from 2688 individual patients from 10 randomized trials
• Clinical stage T2-T4a disease• Platinum based chemotherapy with a
significant benefit to overall survival– 13% reduction in risk of death– 5% absolute benefit at 5 years
• Overall survival increased from 45% to 50%
• No evidence for single agent CDDPLancet 2003; 361: 1927-34
Grossman, H. B. et. al. N Engl J Med 2003;349:859-866
Survival among Patients Randomly Assigned to Receive Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (M-VAC) Followed by
Cystectomy or Cystectomy Alone, According to an Intention-to-Treat Analysis
Grossman, H. B. et. al. N Engl J Med 2003;349:859-866
Survival According to Treatment Group and Whether Patients Were Pathologically Free of Cancer (pT0) or Had Residual Disease (RD) at the
Time of Cystectomy
Grossman, H. B. et. al. N Engl J Med 2003;349:859-866
Survival According to Treatment Group and Whether Patients Had Superficial Muscle Involvement (Stage T2 Disease) or More Advanced
Disease (Stage T3 or T4a)
Conclusions
• Median survival of cystectomy alone was 46 mo c/w 77 mo for combination therapy (p=0.06 by two-sided stratified log rank test)
• In both groups, improved survival associated with the absence of residual cancer in the cystectomy specimen
• Significantly more patients in the combination group had no residual disease than patients in the cystectomy group (38% vs. 15%, p=<0.001)
N Engl J Med 349;9 859-66 August 28, 2003
Diagnosis and StagingThe “Re-Staging TURB”
• 78% of T1 tumors have residual tumor at the time of re-staging TURB
• 25-40% are upstaged to T2
• If no muscle in first biopsy, approximately 50% of pts are upstaged to T2
• If T1 is restaged and remains T1, only 13% are upstaged at time of cystectomy
Herr et al. J Urol, 162: 74-76, 1999Brauer et al. J Urol, 165: 808-10, 2001Dalbagni et al, Urology, 10: 19-24, 2003Dutta et al. J Urol, 166: 490-3. 2001
Radical Cystectomy for T1 TCC
• USC Experience: 208 pts with T1 disease Recurrence Free Survival Overall Survival
5 Year 10 Year 5 Year 10 Year
80% 75% 74% 51%
Stein et al., J Clin Oncol, 19(3): 666-75, 2001
Early Vs. Late Cystectomy
• 90 pts who had TUR + BCG ultimately underwent cystectomy
• 41/90 had T1 disease
• Median Follow up of 96 mosEarly cystectomy (<2 years): 92% survivalLate cystectomy (>2 years): 56% survival
Herr and Sogani, J Urol, 166: 1296-9, 2001
Natural HistoryT1, GIII TCC
• Natural history of T1, G3: -69-80% recurrence rate-33-48% progression rate
• “Rule of 30%” a.) 30% never recurb.) 30% die of metastatic TCC
c.) 30% require deferred cystectomy
Was the Effect all Chemotherapy?Are surgical variables important?
• Post cystectomy survival predicted by:a.) ageb.) stagec.) node statusd.) negative surgical marginse.) >10 nodes removed
• Hazard ratio for death:a.) 2.7 for + surgical marginb.) 2.0 for <10 nodes removed
Herr et al. JCO, 22(14): 2781, 2004
Extent of Lymphadenectomy
• Is there more to the node dissection than staging?
• 1936 Colston and Leadbetter performed studies on 98 cadavers “limited metastatic disease was restricted to the pelvic nodes”
• 1946 – Dr. Jewett “cardinal site of metastasis”
Colston and Leadbetter, J Urol, 36: 669, 1936Jewett et al. J Urol, 55: 366, 1946
Extent of Lymphadenectomy
• Node positive patients can enjoy long term survival
• 24% of grossly node positive disease survived 10 years without adjuvant therapy
• More nodes removed correlates with improved survival
Sanderson et al. Urol Oncol., 22: 205, 2004
Extent of Lymphadenectomy
• Likely no staging advantage to extending the node dissection above the aortic bifurcation
• 33% of unsuspected nodes found at common iliacs
• Practice patterns vary widely:a.) 40% of cystectomies have no LNDb.) 12.7% of LND had <4 nodes removed
Lymph node density (# pos nodes/total # nodes)
Konety et al. J Urol, 170: 1765, 2003
IMA
Genitofemoralnerve
Genitofemoralnerve Aortic
Nodes
Common Iliac Nodes
Hypogastric and Obturator Nodes
Extent of Pelvic Lymph Node Dissection
Herr, H. W. et al. J Clin Oncol; 22:2781-2789 2004
Postcystectomy survival by node status and number of nodes removed
Post Cystectomy Survival
Variable HR* 95% CI P Value
Treatment RC v MVAC + RC 1 0.7 to 1.4 0.97
Age ≥65 v < 65 years 1.5 1.0 to 3.6 0.03
pT stage 3-4 v 0–2 2.3 1.5 to 3.6 0.0002
Node status positive v negative 1.6 1.0 to 2.5 0.04
Margins Positive v negative 2.7 1.5 to 4.9 0.0007
Nodes removed < 10 v ≥10 2 1.4 to 2.8 0.0001
Herr, H. W. et al. J Clin Oncol; 22:2781-2789 2004
T1 Bladder Cancer“Superficial?”
• Balance between over treatment and under diagnosis
• Role of cystectomy
• Intravesical Therapy
Prostate Sparing Cystectomy
• Role for improved continence and potency
• Need to rule out prostate cancer or TCC of prostatic urethra
• Functional Results are good:a.) 97% complete continenceb.) No episodes of retentionc.) 82% maintained potency
Vallancien et al. J Urol, 168: 2413, 2002
Prostate Sparing Cystectomy
• Incidence of Pca is 30-50% with approx. 48% are clinically significant
• 60% of CaP involve the apex (79% significant and 42% insignificant)
• 48% of prostates had urothelial ca involvement of which 33% had apical involvement
• 61% had no prostatic apical involvement of CaP or Urothelial ca.
(6/71-12/97)
USC/Norris Bladder Cancer Experience in 1054 Patients
Probability of Not RecurringAccording to Pathologic Group
0 5 10 15
Years from Cystectomy
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Pro
babi
lity
of N
ot R
ecur
ring
P <0.001
Organ Confined (n=594)
Extravesical (n=214)
Lymph Node (+) (n=246)
(6/71-12/97)
USC/Norris Bladder Cancer Experience in 1054 Patients
Probability of SurvivalAccording to Pathologic Groups
0 5 10 15
Years from Cystectomy
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Pro
babi
lity
of S
urvi
val
P <0.001
Organ Confined (n=594)
Extravesical (n=214)
Lymph Node (+) (n=246)
(6/71-12/97)
USC/Norris Bladder Cancer Experience
Patients with Positive Lymph Nodes (N=246):Probability of Not Recurring
According to Pathologic Groups
0 5 10 15
Years from Cystectomy
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Pro
babi
lity
of N
ot R
ecur
ring
LN+: Organ Confined (n=75)
LN+: Extravesical (n=171)
P = 0.004
(6/71-12/97)
USC/Norris Bladder Cancer Experience
Patients with Positive Lymph Nodes (N=246):Probability of Survival
According to Pathologic Groups
0 5 10 15
Years from Cystectomy
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Pro
babi
lity
of S
urvi
val
LN+: Organ Confined (n=75)
LN+: Extravesical (n=171)P < 0.001
(6/71-12/97)
USC/Norris Bladder Cancer Experience
Probability of Not RecurringAccording to # of Lymph Nodes Involved
0 5 10 15
Years from Cystectomy
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Pro
babi
lity
of N
ot R
ecur
ring
P <0.001
Lymph Node - (n=808)
1-4 Lymph Nodes + (n=160)
> 5 Lymph Nodes + (n=86)
(6/71-12/97)
USC/Norris Bladder Cancer Experience
Probability of SurvivalAccording to # of Lymph Nodes Involved
0 5 10 15
Years from Cystectomy
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Pro
babi
lity
of S
urvi
val
P <0.001
Lymph Node - (n=808)
1-4 Lymph Nodes + (n=160)
> 5 Lymph Nodes + (n=86)
(6/71-12/97)
USC/Norris Bladder Cancer Experience
Incidence of Recurrence Following Surgery:Lymph Nodes Positive TCC (N=246)
0 5 10 15
Years from Cystectomy
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Inci
denc
e of
Rec
urre
nce
Distant Recurrence (f=113)
Local Recurrence (f=28)
Dodd et al, JCO, 1999
Outcome of Postchemotherapy Surgery After MVAC for Advanced Transitional Cell
Carcinoma
Role of Robotics In Bladder Cancer
• Decrease in hospital stay
• Lower morbidity
• Can it compete oncologically?
Conclusion
• Bladder cancer is a multidisciplinary disease
• Surgery plus chemotherapy are the cornerstone of therapy
• New advances in biomarkers and better characterization of T1 disease is necessary