1. Presented by Ahmedin Jemal, DVM PhD
International Patterns in Prostate
Cancer Incidence Trends
MaryBeth Culp, MPH
Presented by Ahmedin Jemal, DVM PhD
NAACCR/IACR 2019
I am presenting on international patterns in prostate cancer incidence rates and trends on behalf of my colleague, MaryBeth Culp., who cannot not be here.

2. Outline Background Data sources and methods Results and discussion
Conclusions
I will start with a brief background, specifically about known risk factors, biology of the disease, and incidence trend in relation to PSA testing in the United States because trends in the US often are bellwether for trends in other countries. Then, I will talk about data sources, Results, and brief Discussion.

3. Risk Factors Older age Race/ethnicity (blacks) Family history
Place of residence (detection practices)
Older age, black race, and family history of the disease and place of residence (degree of detection practice) are the only well-established risk factors for prostate cancer.

4. A Slow Growing Tumor
Median age at diagnosis in the US is 66 years and age at death is 80 years
Colon & rectum (66 vs 70 years), female breast (62 vs 68 years)
Men are more likely to die with prostate cancer than from it
More than a third of men in their 60s and half of men in their 70s and 80s have prostate cancer (Rebbeck et al. Can J Urol 2014)
Indolent cancers that could be detected by PSA testing
Prostate cancer is a slow growing tumor.
Median age at diagnosis of prostate cancer in the US is 66 years and median age at death is 80 years, a 14 year difference between date of diagnosis and date of death. This contrasts with a 4 year for colorectal cancer and six year for female breast cancer, the two other major screenable cancers.
In fact, men are more likely to die with prostate cancer than to die from it
Based on analysis of postmortem data, more than a third of men in their 60s and half in their 70s and 80s have prostate cancer (Rebbeck et al. Can J Urol 2014).
Between 30%-50% of prostate cancer cases diagnosed through PSA testing are indolent cancers that could be detected by increased scrutiny of the prostate gland, such as using PSA testing.

5. Prostate cancer incidence and PSA testing in the US
Prostate cancer incidence rates and trends in the United States over the past 30 years followed changes in the use of PSA testing
Prostate cancer incidence rates and trends in the United States over the past 30 years followed changes in the use of PSA testing
cancer.org

6. Prostate Cancer Incidence & PSA testing, United States
+16.4%
-11.5%
-7.5%
-1.7%
1980: Kuriyama et al. Developed a test to quantify PSA in blood.
1987: PSA testing is more sensitive than PAP, NEJM
2012: USPSTF recommended against routine screening for all men
This graph illustrates trends in prostate cancer incidence rates in the United States in relation to major events in PSA testing.
In 1980, scientists from the Roswell Park Cancer Institute in NY developed a method to quantify prostate-specific antigen in blood.
In 1986, the FDA approved the PSA test for surveillance of prostate cancer patients.
Ans 1987, a paper in NEJM showed that prostate-specific antigen (PSA) is more sensitive than prostatic acid phosphatase (PAP) to detect prostatic cancer and will probably more useful in monitoring responses to treatment and recurrence.
Soon after these events, incidence rates sharply increased by over 16% per year from 1988 to 2012, and dramatically decreased from 1992 through 1995 coinciding with the rise and fall of first time PSA testing during the same time period.
1986: FDA approved PSA to monitor progress in prostate cancer patients
Negoita et al. Cancer 2018

7. First Time PSA Screening Rate in Ages ≥50 Years in the US, 1985-2000
… coinciding with the rise and fall of first time PSA testing during the same time period.
Draisma et al. JNCI 2009

8. Prostate Cancer Incidence & PSA testing, United States
2008: USPSTF recommended against routine screening for men ages 75+
+16.4%
-11.5%
-7.5%
-1.7%
1980: Kuriyama et al. Developed a test to quantify PSA in blood.
1987: PSA testing is more sensitive than PAP, NEJM
2012: USPSTF recommended against routine screening for all men
Another major event in PSA testing is the United States Preventive Services Task Force recommended against screening in men older than 75 in 2018 and in all men in 2012 because of concerns about overdiagnosis and overtreatment associated with PSA testing. Incidence rate significantly declined following these recommendations.
1986: FDA approved PSA to monitor progress in prostate cancer patients
Negoita et al. Cancer 2018

9. Fedewa et al. JAMA Intern Med 2017
Coinciding with decrease in PSA testing
Fedewa et al. JAMA Intern Med 2017
Jemal et al. JAMA 2015

10. PSA Screening Recommendations Update Shared Decision Making
Against Screening
Shared Decision Making
For Screening
United Kingdom – NHS (2015)
US- ACS, AUA (2209)
USPSTF, 2018
Australia and New Zealand– Urological Society (2016)
Canada – CTFPHC (2014)
Japan - Japanese Urological Association (2010)
Mexico - Secretaria de Salud (2010)
Brazil – INCA/Health Ministry (2013)
South Africa – Prostate Cancer Foundation (2013)
European Code Against Cancer (2016)
European Association of Urology (2013)
Following the USPSTF recommendation against screening, many organizations around the world updated their recommendations for PSA testing. Here are a few examples.
The NHS (UK), the Canada Taskforce on Preventive Health Care, Ministry of Health in Brazil, the European Code Against Cancer recommended against routine PSA testing.
While, the Urological society in NZ and Australia, the South Africa Prostate Cancer Foundation, and the European Association of Urololgy recommends screening. t that two European guideline agencies fall on opposite sides of the recommendation spectrum, with the European Code Against Cancer recommending against screening while the European Association of Urology recommends screening.
In the following slide, we will examine how prostate cancer incidence rates in different countries might be related to these and other guidelines from around the world.

11. Objective
Recent changes in international patterns of prostate cancer incidence trends
Changes in recommendations (guidelines)
Spillover effect
Our objective of our study is to examine recent changes in international patterns of prostate cancer incidence trends in view of:
Changes in guidelines (recommendations)
Spillover effect (changes in guidelines in other countries)
cancer.org

12. Data Sources & Methods Data sources Methods
Cancer Incidence in Five Continents: CI5plus
NORDCAN database: incidence for Nordic countries
Methods
JoinPoint model to examine trends in the incidence rates

13. Results and discussion for select countries according to historical uptake of screening
I will present and discuss results for select countries according to historical uptake of screening.
cancer.org

14. Incidence in countries with rapid dissemination of PSA screening
First incidence trends in countries with rapid dissemination of screening, which includes Brazil, Lithuania, and Australia.
Six states in Brazil had campaigns for prostate cancer screening using mobile units beginning in Incidence rates sharply increased during that period and subsequently declined, similar to the incidence trend in the US in late 1980s and early 1990s following PSA introduction.
Similarly, Lithuania introduced national PSA screening program in 2006, and incidence rates more than doubled within 4 years after program implementation and sharply decreased afterwards.

15. Incidence Trends in European Countries with Gradual or Low Uptake of PSA Screening
Gradual Uptake of PSA Screening
Low Uptake of PSA Screening
Uptake of PSA testing in Europe has been mixed. Generally, however, the northern European countries historically were gradual adopters of screening while the eastern European countries had lower rates of screening.
In Northern European countries, prostate cancer incidence rates continued to increase since the early 1990s, without the dramatic peak seen in the United States, Lithuania, or Brazil. However, incidence rates during the most recent period are declining or stabilizing because of reduce pool of prostate cancer or lower utilization of PSA testing.
In contrast, in Eastern European countries, incidence rates are generally lower overall and continue to increase at a much slower pace.

16. Incidence Trends in Countries Where PSA Screening is Uncommon
PSA screening has been uncommon in most Latin American and Asian countries.
In mot Latin American countries, incidence trend is declining or stabilizing perhaps because of spill over effect from the USPSTF recommendations against screening .
In contrast, incidence rate is increasing slowly in some Asian countries, which may reflect increased awareness of the disease and improved surgery for BPH and pathology services, or shared decision making in Japan (2010).

17. Changes in Incidence Rates During the Five Most Recent Data Years (APC)
↑ in 3 countries
→ in 34 countries
↓ in 7 countries
This slide summarize changes in incidence rates during the most recent ten-data years for all 44 countries with high quality incidence data and color coded according to region. The trend in each country is expressed as annual percent change, with values on the x-axis to the left of zero decreasing and to the right of zero increasing.
Out of the 44 countries, incidence rates during the most recent 5-data years increased for 3 countries, stabilized in 34 countries (not shown on this graph) and decreased in 7 countries.
Bulgaria was the country with the largest increasing trend, 17.1% increase in incidence rates.
The largest decreasing trend occurred in the United States with a 7.5% drop, which was also shown in the slide at the beginning of the presentation.
Also, as mentioned previously, Brazil had a statistically significantly decreasing trend in incidence rates of 4.1% in recent years.

18. Limitations Lack of high quality incidence data in many LMICs
Limited information on PSA screening rates and guidelines
A word of caution, however. Interpretation of global variation of incidence data is limited by lack of high quality incidence and mortality data in LMICs. High quality cancer registry cover less than 2% of the population in Africa and 4-6% of the population in Asia and South America.
Furthermore, there is limited information on PSA screening rates and guidelines for many countries, making comparisons between screening and incidence rates within and between countries difficult.

19. Conclusions
Incidence rates declined or stabilized in most high incidence countries:
reduced use of PSA testing (changes in guidelines, or spillover effect)
Or reduced pool of prevalent tumors
Future studies should monitor trends in late-stage disease and prostate cancer mortality to assess the effects of reduction in PSA-testing
Prostate cancer incidence trends in many countries have mirrored the changing guidelines in the United States with initial increasing trends followed by stabilization or decreasing trends. The recent declines seen in many high incidence countries may reflect current lower PSA screening levels or a smaller pool of indolent lesions.

20. Conclusions
Incidence rates continue to increase in some East European and Asian countries which may reflect increased detections
Improved surgery and pathology services
PSA testing

21. Acknowledgements
Isabelle Soerjomataram, PhD Jason Efstahiou, MD, PhD Freddie Bray, PhD
cancer.org