ESMO SUMMIT LATIN AMERICA 2019

Management of prostate

cancer in Latin America

María Teresa Bourlon MD MScUrologic Oncology Clinic

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, México

CONFLICT OF INTEREST DISCLOSURE

• BMS: Honoraria, speaker, advisory board, travel expenses.

• Janssen: Honoraria, speaker, advisory board, travel expenses.

• Asofarma – Astellas: Honoraria, advisory board, travel expenses.

• Bayer: Honoraria, speaker, advisory board.

• MSD: Honoraria, speaker, advisory board, travel expenses.

• IPSEN: Honoraria, advisory board, travel expenses.

• Pfizer: Advisory board, travel expenses.

TABLE OF CONTENTS

1. Epidemiology in Latin America

2. Screening

3. Clinical characteristics of the disease

4. Health care services

5. Barriers to overcome and resource stratification

6. Conclusions

PROSTATE CANCER

In a glimpse

2nd leading cause of cancer death in men.

In developing countries it can be 1st cause.

New case diagnosed every 2.3 minutes

GLOBOCAN: 1,276,106 men diagnosed in 2018 (7.8%).

CA Cancer J Clin. 2018 Nov;68(6):394-424 & American Cancer Society: www.cancer.org

EPIDEMIOLOGY IN LATIN AMERICA

Influencing factors & biases

Int Braz J Urol. 2016 Nov-Dec;42(6):1081-1090. & Cancer Epidemiol. 2016 Sep;44 Suppl 1:S11-S22.

High quality cancer registrations in Latin America cover 6% of the

population vs 96% in the USA and 32-100% in Europe.

Life expectancyof the

population

Inadequate data collection

Available diagnostic methods

Quality of health care

services

Under-Notification

THE CHALLENGECultural & socioeconomic diversity

Diverse health-caresystems, access to care,

socioeconomic, geographic,

environmental, cultural, and ethnic factors.

33 SOVEREIGN STATES

Lancet Oncol. 2013 Apr;14(5):391-436.

GLOBOCAN 2018

Most common type of cancer incidence in 2018 (men)

CA Cancer J Clin. 2018 Nov;68(6):394-424

GLOBOCAN 2018

Most common type of cancer mortality in 2018 (men)

CA Cancer J Clin. 2018 Nov;68(6):394-424

ESTIMATE OF NEW CASES AND DEATHS

Prostate cancer in 2012 and 2030

CA Cancer J Clin. 2015 Mar;65(2):87-108 & Int Braz J Urol. 2016 Nov-Dec;42(6):1081-1090.

Expected increasing incidence and high mortality in Latin America.

INCIDENCE / MORTALITY RATIO OF PC

Compared to gross national product (GNP) per capita per country

CA Cancer J Clin. 2015 Mar;65(2):87-108 & Int Braz J Urol. 2016 Nov-Dec;42(6):1081-1090.

15% compared to breast cancer

x 1.14 breast cancer cases

AWARNESS

Prostate cancer is a neglected disease

Instituto Nacional de Câncer José Alencar Gomes Da Silva. Estimativa 2011. & Int Braz J Urol. 2016 Nov-Dec;42(6):1069-1080.

Brazil (2012): 52,680 new cases Brazil (2012): 60,180 new cases

Brazil (2011): 17 million

gynecological consultations

Brazil (2011): 2.6 million

urological consultations

BREAST CANCER PROSTATE CANCER

EPIDEMIOLOGY IN LATIN AMERICA

Prostate Cancer

Data collection related to incidence an mortality is still precarious.

Prostate cancer is the most common cancer in men in Latin America.

The main cause of cancer related death in many counties.

Central America has the lowest incidence/mortality ratio.

Data reinforces that prostate cancer is a public health priority.

SCREENING Clinical characteristics of the disease

DIVERGENT SCREENING POLICIES

Governmental agencies

Adapted from Int Braz J Urol. 2016 Nov-Dec;42(6):1081-1090.

REGULATORY AGENCY SCREENING RECOMMENDATIONS

NHS (2018) - United Kingdom Not recommended

USPSTF (2018) - USA Not recommended

CTFPHC (2012) - Canada Not recommended

INCA/Health Ministry (2013) -

Brazil

Organized population screening not recommended. If spontaneous demand, inform risks/benefits

INC/Ministerio de Salud de la

Nación (2018) - Argentina

Not recommended

Secretaría de Salud (2018) -

Mexico>55y OR >40y + risk factors

Ministerio de Salud y Protección

Social (2017) - Colombia

Organized population screening not recommended. Early opportunity detection if >50y OR <50y + risk factors.

SCREENING RECOMMENDATIONS

Medical Societies

Adapted from Int Braz J Urol. 2016 Nov-Dec;42(6):1081-1090.

Specialty society Screening recommendations

AUA (2013) - United States40-54y: offer screening if with high risk1

OR 55-69y: offer screening

ACS (2016) - United States>50 years + LE >10 years OR >45 years + high risk1

OR >40 years + very high risk2

EAU (2017) - Europe >50y OR >45 year + familial history or African-Americans

Sociedade Brasileira de Urologia

(2017) - Brazil>50 years OR >45 years + high risk1

Consenso Nacional Inter -

Sociedades (2014) - Argentina 40-49y + high risk1 OR 50-75y

Sociedad Mexicana de Urología

(2017) - Mexico>55y OR >40y + risk factors

Sociedad Colombiana de Urología

(2015) - Colombia

Organized population screening not recommended. Early opportunity detection if >50y or <50y + risk factors.

1 High risk: 1 first-degree relative with prostate cancer or African-american2 Very high risk: >1 first-degree relative with prostate cancer

SCREENING IN LATIN AMERICA

Illiterate patients and economic status (Brazil)

Int Braz J Urol. 2013 May-Jun;39(3):328-34.

Compliance with screening and biopsy findings (N=17,558)

Literacy levels were associated with prior PCa evaluations and

with compliance with screening protocols.

SCREENING IN LATIN AMERICA

Illiterate patients and economic status (Brazil)

Int Braz J Urol. 2013 May-Jun;39(3):328-34.

Illiterate men were at higher risk of being diagnosed with MORE ADVANCED DISEASE.

CLINICAL CHARACTERISTICS Latin Americans in the US: SEER

Oncotarget. 2017 Jul 6;8(41):69709-69721.

Compared with Non-Hispanic White:

Non-Hispanic Black HR 1.15 p <0.001

Hispanic HR 1.02 p=0.534

Compared with Non-Hispanic White:

Puerto Rican HR 1.71 p <0.001

Mexican HR 1.21 p=0.008

Prostate Cancer from 2000-2013 (n= 486,865)

CLINICAL CHARACTERISTICS

Latin America versus Europe/US

Lancet Oncol. 2013 Apr;14(5):391-436.

INCIDENT

CASES MORTALITY

Lesser incidence…..

BUT greater mortality (advanced stages & poor access to care)

CLINICAL CHARACTERISTICS

Selected LATAM cohorts & USA

PLoS One. 2017 Nov 28;12(11):e0188450, Rev Saude Publica. 2017 May 15;51(0):46, Rev Mex Urol. 2016;76(2):76-80 & Acta Med Colomb 2015; 40: 101-108 & & Registro Institucional de Tumores de Argentina

Country NMean

age (SD) I II III IV

5 y

Survival

USA

(2017)110,499 67.1 (9.7) 38.5% 41.7% 14.1% 5.8% 98.2%

Brazil

(2017)16,280 70.5 (8.7) 7.3% 35.1% 25.5% 32.1% 74.4%

Mexico

(2017)238 66.7 (8.8) 8.0% 45.8% 13.4% 32.8% NR

Colombia

(2015)404 69 (8.6) 17.6% 22.0% 34.2% 17.8%

85%

Argentina

(2017)554 NR 10.0% 18.9% 9.3% 61.7% 41%

Clinical stage

GERMLINE MUTATIONS

Lack of information in Latin America

N Engl J Med. 2016 Aug 4;375(5):443-53, J Clin Oncol. 2013 Jan 10; 31(2): 210–216Chavarri Guerra, Bourlon MT, et al Unpublished data. INCMNSZ Mexico City

Unselected for family history or age at diagnosis

Country USA & UK

Total patients N=692

Patients with mutations (%) 82 (11.8%)

Common mutations

(Proportion)

BRCA2 (44%)

CHEK2 (12%)

BRCA1 (7%)

RAD51D (4%)

PALB2 (4%)

RAD51D (4%)

ATR (2%)

NBN (2%)

PMS2 (2%)

MEXICO

(ongoing study)

N=85

2 (2.3%)

MUTYH (50%)

BRIP1 (50%)

Dr. Jeffrey Weitzel

City of Hope Cancer Center

CCGRCN Clinical Cancer Genomics Community

Research Network

APC, ATM, BRCA1, BRCA2,

CDH1, CHEK2, EPCAM, MLH1,

MSH2, MSH6, MUTYH, PALB2,

PMS2, PTEN y TP53.

SCREENING AND DISEASE PRESENTATION

Prostate Cancer

Screening policies are not resource stratified and are not regularly updated .

Available infrastructure to take care of diagnosed cases in screening.

The data comes from small series with limited number of patients.

There is is trend to present with more advanced disease.

The genetic landscape remains unknown.

HEALTH CARE SERVICESPhysicians, infrastructure & drugs

PROSTATE CANCER TREATMENT

Needs according to disease stage

SCREENINGLOCALIZED

DISEASEMETASTATIC

DISEASECASTRATE RESISTANT

Novel agents $Palliative care

CastrationNovel agents $

Surgery Radiation

PSA/DRE

Primary care

UrologistRadiation oncologist

Oncologist

OncologistUrologist

Radiation Oncologist

OncologistPalliative care

UrologistRadiation Oncologist

PHYSICIANS FOR PATIENT CARE

Urologists, radiation-oncologists, medical oncologists & palliative care

DATA FROM A QUESTIONNAIRE

Data published in 2009 regarding the number of urologist and urologic/oncology training.

Urol Oncol. 2009 Mar-Apr;27(2):120-1.

PHYSICIANS FOR PATIENT CARE

Urologists, radiation-oncologists, medical oncologists & palliative care

Radiation therapy services are well below the region`s estimated needs.

Haiti, Belize and Guyana had no radiation services.

ECONOMIST: 40% of the population in Brazil has no access.

https://eiuperspectives.economist.com/sites/default/files/TacklingtheburdenofprostatecancerinLatinAmerica.pdfApdapted from: Lancet Oncol. 2013 Apr;14(5):391-436.

Population in

millionsMedical Oncologists

Number (Rate)

Radiation OncNumber (Rate)

Radiotherapy CentersNumber (Rate)

United States

(2016)329

14,639(4.54)

4,921(1.52)

3848(10.58)

Brazil

(2018)210

3,317(1.57)

644(0.3)

245(1.16)

Mexico

(2017)129

610(0.47)

238(0.18)

125(0.96)

Colombia (2015) 49211

(0.43)59

(0.12)74

(1.51)

All rates are expressed per 100,000 habitants, except RT Centers (1,000,000 habitants)

PHYSICIANS FOR PATIENT CARE

Urologists, radiation-oncologists, medical oncologists & palliative care

Lancet Oncol. 2015 Oct;16(14):1405-38.

UROLOGIC ONCOLOGY TUMOR BOARDS

Mexican Society of Clinical Oncology Survey

Bourlon et al Diagnóstico Situacional de Unidades Funcionales de Uro-Oncología en México. SMEO Qro 2017

Centralized care: Only 5 states reported having a multidisciplinary tumor board.

Mexico has 31 states and 1 capital

ACTIVE SURVEILLANCE PROTOCOLS

Unpublished data in Latin America

Is adherence to surveillance protocol expected? NO.

Lost of insurance or health coverage.

Political parties preferences on the health budget for certain diseases.

PSA DRE

Confirmatory

prostate

biopsy

6-12m

Diagnosis

3-6 months 12 months

Prostate

biopsies

Every 2-5yr

Initial

Chen RC, et al. J Clin Oncol 2016;34:2182-2190 & Sanda MG, et al. J Urol. 2017 Dec 15. pii: S0022-5347(17)78003-2

DISCUSSION OF PC TREATMENT OPTIONS

Do we have the adequate circumstances for decision making?

* We lack published data regarding treatment patterns in Latin America.

Adv Radiat Oncol. 2018 Jan 31;3(2):170-180.

1. The informed-decision treatment selection is not a reality for localized disease.

2. NOT all types of treatments are available for patients.

3. More surgical management than radiation therapy.

4. Treatment decisions may rely more on accessible options.

ACCESS TO THERAPIES

Insurance & available drugs

Adapted from: Lancet Oncol. 2015 Oct;16(14):1405-38.

MEXICO BRAZIL COLOMBIA

HEALTH

SYSTEM

Public health

system (Seguro

Popular)

Social

security

(IMSS)

Government

employees

system

(ISSSTE,

SEDENA,

PEMEX)

Unified public

health care

system

(Sistema

Unico de

Sau de)

Supplemental

health system

(private

insurance)

Unified public

scheme (Plan

Obligatorio de

Salud)

Proportion

of

population

45% 44% 7% 100% 25% 96%

Therapies

GNRH

analogues,

antiandrogens

ketoconazole,

docetaxel,

Abiraterone*,

enzalutamide*

GNRH

analogues,

antiandroges,

ketoconazole,

docetaxel

GNRH

analogues,

antiandrogens,

ketoconazole,

docetaxel,

abiraterone, cabazitaxel,

enzalutamide,Radium 223.

GNRH

analogues,

antiandrogen,

ketoconazole,

docetaxel

GNRH

analogues,

antiandrogens,

ketoconazole,

docetaxel,

abiraterone, cabazitaxel,

enzalutamide

GNRH

analogues,

antiandrogens,

ketoconazole,

docetaxel

SURGICAL VS MEDICAL CASTRATION

PROXIMA prospective registry

Global, prospective registry evaluating real-world treatment patterns of patients with mCRPC.

Timeframe: 2011 to 2014

N=903

J Glob Oncol. 2018 Sep;4:1-12. .

COST EFFECTIVENESS

Example of docetaxel: Hormone sensitive prostate cancer in Brazil

Einstein (Sao Paulo). 2017 Jul-Sep;15(3):349-354.

QALY: quality-adjusted life-year. Years gained and quality of life with that treatment.ICER: incremental cost-effectiveness ratio

OPTIMIZING TREATMENT OF CRPC

Unmet need in Latin America

“Optimizing the treatment of metastatic castration‐resistant prostate cancer:

a Latin America perspective”

Med Oncol. 2018 Mar 19;35(4):56.

CONCLUSION

“Patients should be treated with the

purpose of prolonging overall survival

and preserving quality of life through

increasing the opportunity to

administer all available life-prolonging

therapies when appropriate.”

DISPARITIES IN ACCESS TO NOVEL THERAPIES

Example of docetaxel

Privileged minorities

Tackling the burden of prostate cancer in Latin America: The prospects for patient- centred care is an Economist Intelligence Unit report, sponsored by Janssen. https://eiuperspectives.economist.com/sites/default/files/TacklingtheburdenofprostatecancerinLatinAmerica.pdf

BARRIERS TO OVERCOMEResource stratification

BARRIERS TO HEALTHCARE

Focus on local problems

Lancet Oncol. 2013 Apr;14(5):391-436.

Centralization of resources

Fragmentedhealth care

systems

Language barriers

(indigenous)

Rural/Remote areas

IdiosyncracyProportion withprivate health

insurance

OPTIMIZING TREATMENT OF CRPC

Impact of Prostate Cancer on Economic Measures

Tackling the burden of prostate cancer in Latin America: The prospects for patient- centred care is an Economist Intelligence Unit report, sponsored by Janssen. https://eiuperspectives.economist.com/sites/default/files/TacklingtheburdenofprostatecancerinLatinAmerica.pdf

RESOURCE STRATIFIED GUIDELINES

Focus on local resources in LATAM is lacking

https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/resource-stratified

No Resource Stratified Guideline on

Prostate Cancer

The most common malignant tumor in

the vast majority of Developing Countries

CONCENTRATING & UNIFYING EFFORTS

http://cancerprostata.info/

MOLACAP

MEXICOBRAZIL COLOMBIACOSTA RICA ARGENTINA PERU MEXICO

Regional network of patient organizations commited to improvethe situation of prostate cancer patients in Latin America.

Primary objective: to position prostate cancer as a priority in the public agenda.

Joint report of particular public health priorities

Patient empowerment & information

CONCLUSIONS

Take home messages

PC is the most common neoplasm in Latin American men.

Main cause of cancer related death in several countries.

Less incident cases, but more advanced disease and mortality.

Scarce human resources, health care services and weak organization.

Management of the disease is based more on availability than patient-decision making, lack of multidisciplinary care, poor access to new therapies.

Prostate cancer care and funding is an UNMET need:

Resource adapted consensus and international collaboration.