UPDATES IN SUPERFICIAL BLADDER CANCER

Disclosures  Research Grant Support  American Cancer Society

 Urology Care Foundation / Astellas

 Consultant  American College of Physicians  High Value Care Task Force

 Best Doctors

Matthew E. Nielsen, MD, MS, FACS Lineberger Multidisciplinary Genitourinary Oncology Service Departments of Urology, Epidemiology, Health Policy & Management University of North Carolina at Chapel Hill

Bladder Cancer in the United States  Incidence: >70,000 cases per year  Median age at dx: 74 (incidence peaks in >80yrs)  Heterogeneous risk / natural history

 ~75% non-muscle-invasive (600,000 cases  Intensive lifelong surveillance

 Direct Costs: ~$2.6-3.7B/year  Most expensive per-patient from diagnosis to death  Substantial indirect costs (?) SEER Cancer Statistics; Botteman et al Pharmacoeconomics, 2003

Bladder Cancer in the United States  Incidence: >70,000 cases per year  Median age at dx: 74 (incidence peaks in >80yrs)  Heterogeneous risk / natural history

 ~75% non-muscle-invasive (600,000 cases  Intensive lifelong surveillance

 Direct Costs: ~$2.6-3.7B/year  Most expensive per-patient from diagnosis to death  Substantial indirect costs (?) SEER Cancer Statistics; Botteman et al Pharmacoeconomics, 2003

Low-Risk Bladder Cancer The Elephant in the Room?  Current Guidelines Recommendations

 Epidemiology  Prognosis  Comparative Effectiveness  Costs / Budget Impact

Low-Risk Bladder Cancer  Current Guidelines Recommendations

 Epidemiology  Prognosis  Comparative Effectiveness  Costs / Budget Impact

Surveillance in NMIBC

Surveillance Guidelines: low risk disease American Urological Association:  q3mo x2y; q6mo x 3y, annually thereafter  No explicit risk stratification

 “Reset” at recurrence (50-85% by 5 years); lifelong  Acknowledge possible acceptability of lower intensity

in select cases (not specified)

https://www.auanet.org/education/guidelines/bladder-cancer.cfm

Surveillance Guidelines: low risk disease  EAU: explicit risk stratification (calculator)  Low risk (LGTa 50

Secondary

90

NONINVASIVE

INVASIVE High Grade T1 CARCINOMA IN SITU

Donat SM, Urol Clin N America 2003

 9167 patients with prior adenoma  Median follow-up 47.2 months

 Advanced CR neoplasia 11.8% (1082) (≥10mm, HG dysplasia, >25% villous)  ≥5 lesions: 24% risk; >20mm lesion 19.3%

 Invasive CRC (T2 disease): 0.6%  ≥5 lesions: 1.2% risk; >20mm lesion 0.8%

Low Grade Noninvasive Bladder Cancer  40-50% of incident cases—on the rise?  Relatively indolent natural history  Risk = recurrence of low-grade lesions

 Rare grade / stage progression  High vs. Low grade: distinct molecular biology  Majority of prevalent cases

 Lack of consensus in practice guidelines  Paucity of data on outcomes, survivorship

experience, decision making, patient perceptions of risk

Low-Risk Bladder Cancer  Epidemiology

 Prognosis  Current Guidelines Recommendations  Comparative Effectiveness  Costs / Budget Impact

Models in Research

“A model is a lie that helps you see the truth.” Howard Skipper, PhD (Sebring, FL native)

Simulation Modeling in CER  National Research Council:  “A replicable, objective sequence of computations

used for generating estimates of quantities of concern.”

 Synthesize evidence on health consequences

and costs in a logical structure to inform health decisions—ISPOR  Ruth Etzioni et al. {CISNET}

UNC-NCSU collaboration  Brian Denton and Yuan Zhang  NCSU Industrial Engineering / Operations Research

 Developed cohort simulations (POMDP) of

low grade noninvasive bladder cancer  Evaluate different guidelines for surveillance

 Model age-specific and dynamic policies  Sensitivity analyses:

 Age (competing risks)  Disutility of cystoscopy

Comparative Effectiveness (Prelim)  Expected life-long T2 progression rate  AUA: 6.2% (15 cystoscopies)  EAU: 6.6% (8 cystoscopies)

 Sensitivity analyses:  Disutility of cystoscopy  Other-cause mortality / age at diagnosis

 Limitationsfuture directions (ACS MRSG):  Microsimulation to reflect population age

distribution  Costs, Empiric utility estimates

What Defines Quality Care?  “The extent to which health services for individuals and populations increases the likelihood of desired health outcomes and is

consistent with current professional knowledge” -Institute of Medicine  What is the appropriate intensity of care?  Risk of harm/mortality from malignancy?

 Differential risks by cancer site  Differential risks within a given cancer site  Potential harm from competing risks?

Low-Risk Bladder Cancer  Epidemiology

 Prognosis  Current Guidelines Recommendations  Comparative Effectiveness  Costs / Budget Impact

costprojections.cancer.gov

JNCI 2009; 101: 571-80

AUA/EAU Surveillance Cost Comparison =Budget Impact Analysis Component of Medicare Billed Cost Low ProtocolGrade Ta SURVEILLANCE COSTS Level 3 Office Visit

Year 1

Cystoscopy

Year 2

$276

Year 3

Cytology EAU Guidelines

$2,228

Year 5

Five-Year Total Cohort Surveillance Cost

$312.65

Total Per Visit

Low-risk

Year 4

$525

Five-Year Per Patient Total Surveillance Cost

$1,114

$1,114

$1,114

$1,114

$1,114

$6,684

$235,711,260

$4,456

$2,228

$2,228

$1,114

$14,482

$510,707,730

AUA Guidelines All Patients

$4,456

 54% total savings over 5 years  $7,798 per patient; $274,966,470 total population  [For one year’s worth of incident cases]

Future Directions  Granular population-based data needed for

model validation  Risk stratification: tailoring interventions to maximize effectiveness  Integration of molecular markers in practice

 Refine classification (molecular grading)—validation  Possible substitute for surveillance cystoscopy

 Pragmatic trial of different surveillance regimens  A role for emerging AUA-led registries?

Thank You

Email: [email protected] Twitter : @m_e_nielsen