Prostate cancer: an emerging threat to the health of aging REVIEW

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Asian Journal of Andrology (2011) 13, 574–578
ß 2011 AJA, SIMM & SJTU. All rights reserved 1008-682X/11 $32.00
www.nature.com/aja
REVIEW
Prostate cancer: an emerging threat to the health of aging
men in Asia
Ling Zhang1, Bao-Xue Yang1, Hai-Tao Zhang2, Jin-Guo Wang1,3, Hong-Liang Wang1,3 and Xue-Jian Zhao1,3
The aim of this study was to determine and examine the possible reasons for the difference in prostate cancer incidence between Asian
men and North American men by literature review. Data regarding cancer incidence and mortality were obtained from the database of
the International Agency for Research on Cancer (IARC). A literature review was conducted by studying related articles published in
peer-reviewed journals such as the The New England Journal of Medicine, Journal of Clinical Oncology, A Cancer Journal for Clinicians
and Asian Journal of Andrology. To evaluate the early diagnosis and survival rates, the mortality-to-incidence rate ratio (MR/IR) was
calculated from the IARC data. By comparing prostate cancer data between Asian men and North American men, we found that
differences in the incidence rate and MR/IR could be attributed largely to a lack of annual prostate cancer screening with serum
prostate-specific antigen (PSA) in most Asian countries. It is likely that PSA screening also contributes significantly to the differences
in prostate cancer mortality rates. Prostate cancer has the highest incidence rate among five common malignancies in Asian
Americans. However, the MR/IR ratio of prostate cancer is the lowest among cancers. These data seem to further support the usefulness
of PSA screening, even though the percentage of low risk cancers is greater in prostate cancer than in other cancers. The low incidence
rate of prostate cancer does not reflect the actual statistics of this disease in Asia. The data from limited institutions in many Asian
countries seem to bias the true incidence and mortality rates. To improve this situation, incorporating PSA screening for prostate
cancer, as well as constructing a nationwide cancer registration system, will be helpful.
Asian Journal of Andrology (2011) 13, 574–578; doi:10.1038/aja.2010.126; published online 9 May 2011
Keywords: Incidence; mortality; prostate cancer; prostate-specific antigen
INTRODUCTION
The trend of an aging population presents a serious socioeconomic
problem in Asian countries. The population over 60 years old in Asia is
about four times greater compared to those of North America and
Europe.1 Thus, health problems will be a greater burden in Asian
countries despite rapid socioeconomic growth. Cancer is commonly
associated with aging, and early diagnosis is the only way to improve
treatment results and lower cancer mortality. For example, the 5-year
survival rate of patients with prostate cancer when diagnosed and
treated in the early stages is nearly 99%.2
Prostate cancer is diagnosed mostly in men above 50 years of age.
However, the incidence and mortality rates of prostate cancer are very
low in Asian men, and so it has not been considered a major threat in
this population. According to the 2002 data from the International
Agency for Research on Cancer (IARC), the United States had the
highest prostate cancer incidence rate in the world at 124.8/105 person
year (PY).
The incidence rate of prostate cancer in China was 1.6/105 PY,
which ranked 170th. Other countries in Asia, including Japan (12.6/
105 PY, 114th), Korea (7.6/105 PY, 134th) and Vietnam (2.8/105 PY,
161st), were also reported as having low incidence rates.3 Such a large
difference in the prostate cancer incidence rate between North
America and Asia cannot be entirely explained by variations in diet,
race and environmental factors,4,5 and this fact is a cause of concern
for many researchers.
THE DIFFERENCE IN PROSTATE CANCER INCIDENCE RATES
BETWEEN NORTH AMERICAN AND ASIAN MEN COULD BE
DUE TO A DIFFERENCE IN PROSTATE-SPECIFIC ANTIGEN
(PSA) SCREENING PREVALENCE
In 2006, Kamangar et al.6 described the overall cancer incidence,
mortality and prevalence of lung, breast, colon and rectum, stomach,
prostate, liver, cervix and oesophageal cancer in selected geographic
regions of the world using GLOBOCAN (2002) and five-continent
databases from the IARC. The incidence rate of prostate cancer in
North America (119.9/105 PY) was nearly 25.5 times higher than that
of Asia (4.7/105 PY). However, the mortality rate of prostate cancer in
North America was only 5.9 times higher than that in Asia (15.8/105
PY versus 2.7/105 PY). The authors stated that the enormous difference between the two continents could not be explained by variations
in diet and race, and they concluded that annual screening for prostate
cancer with a serum PSA measurement in men of 50 years or older in
North America is likely another significant contributing factor. The
authors used the mortality-to-incidence rate ratio (MR/IR) as an
indirect index for the evaluation of survival and early diagnosis. The
MR/IR ratio was 0.13 in North America. This means that that there
1
Prostate Diseases Prevention and Treatment Research Centre, Jilin University, Changchun 130021, China, 2Department of Pathology and Laboratory Medicine, Tulane
University School of Medicine, New Orleans, LA 70131, USA and 3Department of Andrology, First Hospital of Jilin University, Changchun 130021, China
Correspondence: Professor HL Wang ([email protected])
Received: 7 September 2010; Revised: 22 December 2010; Accepted: 4 January 2011; Published online: 9 May 2011
Prostate cancer: an emerging threat in Asia
L Zhang et al
575
were 13 deaths for every 100 newly diagnosed prostate cancer patients.
The MR/IR in Asia was 0.57. The small value for MR/IR in North
America may provide further supporting evidence that vigorous
annual screening with PSA is feasible and may reduce prostate cancer
mortality.
The worldwide prostate cancer MR/IR ratios from IARC decreased
markedly from 2002 to 2008.3,7 As shown in Table 1 and Figure 1, new
prostate cancer cases worldwide have increased from 679 060 to 914
000 during this period. Prostate cancer incidence rate has increased
from 25.3/105 to 28.5/105 PY, while mortality rate has decreased from
8.2/105 to 7.5/105 PY. The MR/IR ratio has decreased from 0.32 to
0.26. The prostate cancer incidence rate in North America has
decreased from 119.9/105 to 85.7/105 PY, and the mortality rate has
decreased from 15.8/105 to 9.9/105 PY, accompanied with a decrease in
the MR/IR ratio from 0.13 to 0.12. Of all the continents, Europe had
the most remarkable change. The prostate cancer incidence rate
increased from 40.0/105 PY in 2002 to 61.4/105 PY in 2008.
However, the mortality rate decreased from 14.2/105 to 12.1/105 PY
and the MR/IR ratio decreased from 0.36 to 0.20. This remarkable
progress could be attributed to the European Randomized Study of
Screening for Prostate Cancer.8 Although Asia and Africa have made
some improvements in mortality rates and MR/IR ratios, the changes
are modest compared to other continents.
REASONS FOR THE LOW INCIDENCE AND HIGH MR/IR RATIO
OF PROSTATE CANCER IN ASIA
As showed in Table 1, the prostate cancer incidence rate in Asia was
7.2/105 PY, and the mortality rate was 3.2/105 PY, which were markedly lower than that of other continents. The MR/IR ratio (0.44) was
significantly higher than that of other continents, except for Africa.
These results indicate that prostate cancer in Asia may be very small in
number, but it is a very high risk disease when compared with that in
other continents. However, do these results reflect reality?
Age-standardized incidence rates, mortality rates and MR/IR ratios
in Asia
The data in Table 2 come from the IARC databases.7 The MR/IR ratios
in Japan, Korea and Singapore had decreased to 0.22, 0.18 and 0.20,
respectively, which were very close to those in Europe (0.20) and
North America (0.12). In Japan, the early diagnosis of prostate cancer
started a relatively long time ago, and Japanese urologists pay attention
to and take an active part in the early diagnosis and treatment of
prostate cancer.9 In 2008, the incidence rate of prostate cancer in
China was 4.3/105 PY, much higher than that in 2002 (1.6/105 PY).
Meanwhile, the mortality rate decreased from 0.62 to 0.42. These
results demonstrate that prostate cancer can be detected at an early
stage and that treatment can be effectively performed.10 However, it
should be noted here that the incidence and mortality rate data mostly
came from limited clinical institutes and not from mass screening
results. In Philippines, Vietnam and Malaysia, the MR/IR ratios were
over 0.50. It may be shown in these countries that prostate cancer is
only diagnosed at late clinical stages. In a late cancer stage, life expectancy and quality of life are considered poor.
The incidence rates of prostate cancer among Asian Americans are
not low
In 2007, McCracken et al.11 compared prostate cancer incidence and
mortality rates for ethnic groups of Asian Americans with those of
non-Hispanic whites. The data were provided by the Los Angeles
Cancer Surveillance Program and the California Cancer Registry from
2000 to 2002. The incidence rate among non-Hispanic whites was
159.9/105 PY. Among all Asian ethnic groups, Filipino Americans
had the highest incidence rates (113.3/105 PY). The incidence rates
of Japanese Americans, Chinese Americans and Vietnamese
Americans were 103.4/105, 80.4/105 and 65.4/105 PY, respectively.
Korean Americans had the lowest incidence rate (51.0/105 PY).
There were obviously some differences between Asian Americans
and non-Hispanic whites, which might truly be associated with variations in race and lifestyle, particularly dietary differences.12,13
Furthermore, the incidence rates among Asian Americans were significantly higher than the average level (4.7/105 PY) in Asian men
living in their homeland.11 The MR/IR ratio is probably the most
valuable indicator of cancer survival and an early diagnosis. As stated
previously, the prostate cancer incidence rate (51.0–113.3/105 PY)
varied significantly among the Asian American ethnic groups; however, MR/IR ratios (0.111–0.146) were lower than that of nonHispanic white men (0.169). These results indicate that the incidence
and mortality rates of Asian people are expected to be greatly
improved, even in their homeland, by increasing PSA screening.
The comparison of incidence rates and MR/IR ratios of five
malignant tumours among Asian Americans
McCracken et al.11 calculated MR/IR ratios based on the incidence and
mortality rate data of five malignant tumours (Table 3). Despite the
fact that prostate cancer was the most commonly diagnosed cancer
among Asian American men, except for Korean and Vietnamese
Americans, the MR/IR ratios of prostate cancer were significantly
lower than those of lung, liver, stomach and colon/rectal cancers. All
five malignant tumours could be detected by mass screening, but why
were the MR/IR ratios of prostate cancer lower than that of the other
four cancers? PSA is secreted by the prostate gland epithelial cell and is
a tissue-specific antigen of the prostate. Adenocarcinoma cells have
the ability to secrete PSA into interstitial fluid and elevate the serum
PSA level. Because the prostate gland is of parenchymatous organ,
prostate cancer can be diagnosed easily and safely by ultrasoundguided systematic biopsy. PSA mass screenings annually performed
in North America have increased patient diagnoses at early stages
and facilitated efficient treatment. One study has demonstrated that
Table 1 Worldwide age-standardized incidence rates, mortality rates and mortality-to-incidence rate ratios (2008)7
World
North America
Oceania
Europe
South America
Asia
Africa
Cases
Incidence rate (cases/105 PY)
Death
Mortality rate (cases/105 PY)
MR/IR ratio
913 770
213 705
21 428
385 440
84 111
133 171
39 460
28.5
85.7
94.5
61.4
50.2
7.2
17.5
258 381
32 591
4294
89 908
29 274
59 643
28 006
7.5
9.9
15.3
12.1
16.2
3.2
12.5
0.26
0.12
0.16
0.20
0.32
0.44
0.71
Abbreviation: MR/IR, mortality-to-incidence rate ratio.
Asian Journal of Andrology
Prostate cancer: an emerging threat in Asia
L Zhang et al
576
Systematic multiple biopsies, as performed in the prostate, are usually
not suitable for a secondary examination. In addition, prostate cancer
is generally slow growing in nature compared to other cancers, especially low-risk cancers with a PSA ,10 ng ml21 and a Gleason score
,7, which seems to the reason that the four other cancers are diagnosed at a later clinical stage compared to prostate cancer.
Figure 1 Worldwide age-standardized incidence rates, mortality rates and mortality-to-incidence rate ratios.7 MR/IR, mortality-to-incidence rate ratio.
the 5-year survival rate of clinically localized prostate cancer reaches
99%.2 Although lung, liver, stomach and colon/rectum cancers have
their respective markers, they are generally useful only at advanced
clinical stages. These cancers can be diagnosed mainly by imaging
procedures such as X-ray examinations including computed tomography, magnetic resonance imaging or endoscopic examination.
PREVALENCE OF PSA SCREENING IN MEN OVER 50 YEARS
OLD IS IMPERATIVE IN ASIAN COUNTRIES
The analysis of prostate cancer incidence rates and the MR/IR ratios
suggests that the incidence rates were not in fact low in the Asian
population. The fact that MR/IR ratios were significantly lower in
Asian Americans than in white Americans suggests that the prevalence
of PSA screening will make it possible to detect prostate cancer at early
stages and treat the disease efficiently in Asian countries. In addition,
our group has conducted a PSA-based prostate cancer screening in
men over 50 years old in Changchun, China. The results showed that
the overall prostate cancer detection rate in this cohort was 1.7%.
However, cases with Gleason scores 8–10 accounted for 34% of all
prostate cancer cases.10,14–16 Our data suggest that the prostate cancer
incidence rate in China would be almost equivalent to those of Europe
and the United States; prostate cancer is prevalent in developing Asian
countries and the mortality risk can no longer be ignored.
Furthermore, the data suggest that the rate of high-risk patients may
be variable and dependent on lifestyle and/or ethnic background from
country to country.
Prostate cancers with Gleason scores f6 are classified as welldifferentiated cancers. This kind of prostate cancer has the lowest
invasive potential, often forms a carcinoma nodus and develops
slowly. When the carcinoma nodus grows into the urethra, it will
result in difficult urination, which forces the patient to the hospital.
However, if difficult urination is due to the cancer, it is likely at an
advanced stage and the best opportunity for treatment may have been
lost. These are the prostate cancer patients that urologists can usually
detect in the clinic. Some urologists in China look at prostate cancer as
a very slow-growing cancer that is not life threatening in nature. These
traditional views sometimes result in mismanagement and allow the
cancer to metastasize.
Prostate cancers with Gleason scores o8 have highly invasive abilities, and micrometastases are often present even at an early stage.17
Prostate cancer cells of this type will demonstrate the ability for infiltrative growth into the interstitial space instead of forming a carcinoma nodus that often oppresses the urethra. In such cases, patients will
not have any genitourinary symptoms leading them to visit an urologist even in advanced stages until metastases symptoms develop. An
early stage cancer generally shows no symptoms; therefore, in order to
detect the cancer early, a mass screening system is important.
Measurement of the serum PSA has been recognized worldwide as a
safe and cost-effective method for detecting prostate cancer, and it is
Table 2 Age-standardized incidence rates, mortality rates and mortality-to-incidence rate ratios in Asia (2008)7
China
Japan
Korea
Singapore
Philippines
Vietnam
Malaysia
Cases
Incidence rate (cases/105 PY)
Death
Mortality rate (cases/105 PY)
MR/IR ratio
33 802
38 619
6382
616
2491
1208
821
4.3
22.7
22.4
20.0
10.1
3.2
9.2
14 297
9989
1204
125
1290
716
508
1.8
5.0
4.1
3.9
5.3
1.9
5.8
0.42
0.22
0.18
0.20
0.52
0.59
0.63
Abbreviation: MR/IR, mortality-to-incidence rate ratio.
Asian Journal of Andrology
Prostate cancer: an emerging threat in Asia
L Zhang et al
577
Table 3 The comparison of age-adjusted incidence rates, mortality rates and mortality-to-incidence ratios for five kinds of cancers between
Asia Americans and white Americans (per 100 000)11
Prostate cancer
Lung cancer
Colon/rectum cancer
Stomach cancer
Liver cancer
IR
MR
MR/IR
IR
MR
MR/IR
IR
MR
MR/IR
IR
MR
MR/IR
IR
MR
MR/IR
Chinese
Filipino
Vietnamese
Korean
Japanese
Non-Hispanic white
80.4
8.9
0.11
52.3
46.6
0.89
52.2
18.2
0.35
18.3
14.1
0.77
23.3
19.9
0.85
113.3
15.7
0.14
71.9
49.8
0.69
48.4
16.6
0.34
7.2
4.1
0.57
16.8
12.0
0.71
65.4
9.1
0.14
72.8
47.2
0.65
39.1
11.1
0.28
28.1
15.5
0.55
54.3
35.5
0.65
51.0
7.1
0.15
56.3
52.3
0.93
57.8
19.1
0.34
54.6
35.2
0.65
33.7
26.6
0.79
103.4
15.1
0.14
41.1
36.0
0.88
57.8
27.1
0.42
27.0
18.1
0.67
9.3
8.3
0.89
159.9
27.0
0.17
77.9
64.0
0.82
57.8
21.3
0.36
9.5
5.0
0.53
6.8
6.0
0.88
the only effective method to detect prostate cancer at an early stage.
The percentage of prostate cancers with a Gleason score o8 was 34%
according to data from the PSA mass screening in Changchun,
China.16 Stamey et al.18 also showed that the percentages of tumours
with a Gleason score o8 during four successive 5-year periods were
30.89%, 26.82%, 28.00% and 35.03%, respectively, from 1983 to 1988.
These results indicate that PSA screening can result in the early diagnosis and treatment of prostate cancer as well as the detection of early
stage cancer, but cannot change the pathological grade. PSA mass
screening can diagnose cancer irrespective of its malignancy; highly
malignant prostate cancer can also be detected at its early stage without
metastasis allowing for curative treatment. For this reason, both the
incidence rates and the MR/IR ratios significantly decreased in 2008
compared with those in 2002 in the IARC data.3,7
On the other hand, PSA screening would lead to an overdiagnosis
and overtreatment for tumours with a Gleason score f6.19,20 The
American Cancer Society pays great attention to the issue of overdiagnosis and overtreatment and emphasizes providing sufficient
information about screening to allow participants to make an
informed decision. The American Cancer Society recommends that
men should begin to receive PSA screenings at age 50. Men at higher
risk should receive screening from the age of 45. For men whose PSA is
,2.5 ng ml21, screening intervals can be extended to every 2 years.
With a PSA level between 2.5 and 4.0 ng ml21, screening should be
conducted annually. Men with a PSA level o4.0 ng ml21 are recommended to be referred for further evaluation or a prostate biopsy.21
The effect of prostate cancer screening on prostate cancer mortality
was observed in two similar studies with different results. The United
States-based Prostate, Lung, Colorectal, and Ovarian Cancer
Screening Trial indicated that the death rate from prostate cancer
was very low and did not differ significantly between a PSA screening
group and a control group.22 However, Hugosson et al.23 found that
PSA-based population screening for prostate cancer led to a 44%
reduction in prostate cancer disease-specific mortality. Higher contamination with opportunistic screening of the control group was
thought to be the reason for the contradicting results of the US study.
PSA screening rates in Asian developing countries are still very low,
and even in Japan, the percentage of men over 50 years of age who
received PSA screenings was estimated to be less than 20%.24 Men had
little opportunity to take part in a screening in most Asian countries if
they were not invited. Similar trials are needed to evaluate the effects of
PSA screening on prostate cancer mortality in Asia.
SUMMARY
In this review, we have examined the possible reasons for the difference
in prostate cancer incidence rates and MR/IR ratios between Asia and
North America. Annual screening for prostate cancer with PSA in
aging men in North America leads to early detection and treatment
at as early a stage as possible. A nationwide cancer screening system
results in the detection of numerous cancer patients at an early stage
and leads to a higher prostate cancer incidence rate and lower MR/IR
ratio. The higher prostate cancer incidence rates among Asian
American men suggest that the incidence rate in native Asian men
would be much higher if they received annual PSA screening. The low
MR/IR ratio in Asian American men is equivalent to that of NonHispanic whites and is the lowest of five kinds of malignant tumours,
suggesting that PSA screening has the potential to improve prostate
cancer mortality and increase the cancer detection rate because the
tumour marker has a high specificity. Therefore, PSA mass screening
should be promoted more vigorously in Asian countries.
COMPETING FINANCIAL INTERESTS
The authors declare no competing financial interests.
ACKNOWLEDGMENTS
The authors are grateful to Professor Masaaki Kuwahara for his critical reading
and revising of our manuscript. This work was funded by the National Natural
Science Foundation of China (Nos. 30801354 and 30970791) and Jilin
Provincial Science & Technology Department China (No. 20080154).
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