ibcu invasive panel discussion - grand rounds in urology · 2019-01-24 · preadmission counseling...
TRANSCRIPT
Invasive Bladder Cancer Panel Discussion
Michael S. Cookson, MD, MMHC, FACSProfessor and Chair
Department of Urology, University of Oklahoma
Case Based Discussion
• Patient selection • Perioperative Management• Neoadjuvant Therapy• Surgical Approach• Role of Lymph Node Dissection• Adjuvant Treatment
History• 56 yo male seeks a second opinion regarding new
diagnosis of muscle-invasive bladder cancer• Presented with painless gross hematuria for 6weeks• ROS: 10 lbs. weight loss • PMH: HTN, Type2 DM, Hypercholesterolemia• SH: Nonsmoker, works in rubber tire manufacturing• AUASS 2, SHIM 21, ECOG 0
Clinical Information
• Physical Exam: Moderately obese (BMI 31)• CT Chest: No evidence of metastatic disease• CT Abdomen: Large tumor on the left lateral wall• Cysto/TURBT: Large sessile tumor on left lateral wall
mass; No other areas of concern– Path: High-grade (III/III) urothelial carcinoma invasive into
muscularis propria
• sCre 1.5 ng/dl (eGFR > 65), LFT’s within normal limits
Vale, et al Eur Urol 48:202, 2005
Neo-adjuvant Chemotherapy Meta Analysis5% Survival Advantage
• Individual patient data from 6 randomized trials• 9% survival benefit with platinum-based combinations
Cisplatin alone
Cisplatin combo
SWOG S1314
COXEN Validation Neoadjuvant
Chemotherapy Trial
Selection Criteria SWOG 8710
(T2-T4a N0M0, cisplatin eligible)
C
Y
S
T
E
C
T
O
M
Y
Randomize
to chemo
n=184
Gem-Cis
DD-MVAC
AssessmentTo characterize the
relationship of MVAC-
and GC-specific COXEN
scores in terms of pT0
rate
Biomarker validation and Biomarker discovery
Tumor
Sample
TURBT
CollectionTissue, blood, urine
Molecular AnalysisGene expression
Sequencing
microRNA
SNP
CollectionTissue (>P0), blood, urine
Molecular AnalysisGene expression
Sequencing
microRNA
SNP
Cystectomy
Pathology
Discovery
Activated July 1, 2014
Panel Discussion: Next Steps • Neoadjuvant chemotherapy (NAC) or upfront radical
cystectomy? –What factors influence NAC decision?• Radiographic T3/T4 disease• Variant histology• Hydronephrosis• Other?
–What if renal function is poor?– What is the role of repeat TUR prior to NAC?– Should complete TURBT be performed?
Assessment after NAC
• Patient received 3 cycles of Gemcitabine and Cisplatin which he tolerated well
• What is the role of restaging after NAC?– Imaging? –Repeat TUR-BT
• Does the absence of residual bladder cancer on repeat TUR-BT (cT0) influence decision making?
Preadmissioncounseling
No/selective bowel-prep
Fluid and carb loading/no prolonged fasting
No premed
No NG tubes
Mid-thoracic epidural anesthesia/analgesia
Short-acting Anesthetic agent
Avoidance ofSodium/fluid overload
No drains
Warm air bodyheating in surgery
Earlymobilization
Non-opioid oralanalgesia/NSAIDs
Prevention of nausea and vomiting
Stimulation of gut mobility
Early removal ofcatheters/drains
Earlyoral nutrition
Audit of compliance/outcomes
Core ERAS Protocol
ERAS
AntibioticprophylaxisThrombo-
prophylaxis
Avoidance of saltand water overload
PREOPERATIVE
INTRAOPERATIVEPOST
-OPE
RATIV
E
ERAS® Society. http://www.erassociety.org/index.php/eras-care-system/eras-protocol
Panel Discussion:Perioperative Interventions to Reduce
Morbidity of Radical Cystectomy• What is the role of Immunonutrition?– Pre-habilitation (exercise, shakes, smoking cessation) – How do you do it?
• Comment on enhanced recovery after surgery (ERAS) care pathways?– Bowel prep (ever vs. never vs. special circumstances)– Alvimopan (Entereg�)?– Epidural?– Duration of DVT prophylaxis– Discharge management
NCDB Data: Robotic RC
Bachman AG, et al, Urology, 2017
Almost 40% of cystectomies
are now performed by
minimally invasive
approach—and favored in
lower volume and non
academic centers
Comparison Points
Oncologic Outcomes Morbidity
Learning Curve Cost
Panel Discussion: Surgical Approach
• Robotic vs. open radical cystectomy?• If robotic, what about the diversion? –Intracorporeal vs. open diversion
Cancer-Specific Survival in Robotic vs Open: SEER-data
Hu JC et al, European Urology, 2016
NO DIFFERENCE IN CANCER-SPEC SURVIVAL: follow-up 44 mos
Xia L, Wang X, Xu T, Zhang X, Zhu Z, et al. (2015) Robotic versus Open Radical Cystectomy: An Updated Systematic Review and Meta-Analysis. PLoS ONE 10(3): e0121032. doi:10.1371/journal.pone.0121032
Meta Analysis: Outcomes that Favor the RobotBlood Loss Transfusion LOS
• First phase 3 multicenter randomized evidence comparing oncological outcomes of ORC to RARC
• Primary endpoint of 2-year progression free survival
• All surgeons fellowship trained or bladder cancer focused Parekh D et al. Lancet 2018; 391: 2525–36
RAZOR Trial
“robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival.”
Parekh D et al. Lancet 2018; 391: 2525–36
0 5 10 150.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Prob
abili
ty o
f Not
Rec
urri
ng
P <0.001
Organ Confined (n=594)
Extraves ical (n=214)
Lymph Node (+) (n=246)
Recurrence-Free SurvivalUSC/Norris Cancer Center-Open
Stein JP et al: J Clin Oncol 19:666-75, 2001
Lymphadenectomy: Where�s the Line?
Iliac Artery Bifurcation
Common Iliac Artery
Aortic Bifurcation
Inferior Mesenteric Artery
Panel Discussion: Surgical Approach
• Extended lymph node dissection: Is it really necessary? If so, what are the boundaries?
• What to do with N+ disease post-cystectomy? • Should adjuvant treatment always be given,
and if so—what and when?
Fig. 2 Pooled hazard ratios across all nine studies by chemotherapy type CI = confidence interval; ES = effect size.
Adjuvant Chemotherapy for Invasive Bladder Cancer: A 2013 Updated Systematic Review and
Meta-Analysis of Randomized Trials
Leow, et al Eur Urol epub 8/2013
945 patients in 9 trialsHR 0.77 - 23% relative reduction in Death
• AUA/SUO: Patients with RC path pT3/T4and/or N+ who have not received cisplatin-based NAC should be offered adjuvant cisplatin- based chemotherapy. (Moderate Recommendation; Evidence Level: Grade C)
• EAU and ASCO: Data are not convincing enough to give an unequivocal recommendation for the use of immediate adjuvant chemotherapy as compared to chemotherapy at the time of relapse (1A)
• NCCN: Consider if pT3-4, any N+, if no NAC given (2B)
50
Adjuvant ChemotherapyGuidelines – AUA/SUO, EAU, ASCO