Absolute numbers and age-standardised rates of incidence and mortality for selected regions and countries 
This chapter presents the current state of prostate cancer epidemiology and compares data from different regions. The data are taken from several sources:
Globocan 2008  gives a glance on the worldwide situation in cancer epidemiology and permits the comparison of more and less developed regions in every continent.
The “Surveillance, Epidemiology and End Results” Program (SEER)  in the USA and the Robert Koch Institute (RKI)  in Germany present epidemiologic data of highly industrialized nations with maximally developed medical systems.
The Munich Cancer Registry (MCR) , a population-based clinical cancer registry of Upper Bavaria, an area of 4.5 million inhabitants in the South of Germany, presents detailed analyses of clinical data, distributions of prognostic factors and therapy, and survival analyses. Data of the MCR have also contributed to the publication “Cancer Incidence in Five Continents, Volume IX” .
2. Incidence and mortality
In Table 1 absolute numbers and age-standardized rates of incidence and mortality are presented for selected regions and countries . In 2008 it was estimated that nearly every seventh case of male malignoma was prostate cancer (899 thousand new cases, 13.6% of the total). Therefore, in men prostate cancer was the second most diagnosed cancer after lung cancer. Approximately three quarters of these cases were diagnosed in more developed countries. The highest incidence rates were measured in Australia, New Zealand, Northern and Western Europe and Northern America. Moderate incidence rates were found in South America and Eastern Europe. The lowest incidence rates were reported from South-Central Asia.
|More developed regions||644||61.7||136||10.5|
|Less developed regions||255||11.9||121||5.6|
|Australia and New Zealand||21.0||104.2||4.0||15.4|
|Central and Eastern Europe||58.4||29.1||23.1||10.9|
|Absolute numbers in thousands; ASR (W): age standardised rate per 100,000 by world standard|
Despite its high proportion of cancer diagnoses, prostate cancer is the cause of cancer specific death in only every 16th case (258 thousand deaths, 6.1% of the total). This places prostate cancer on the sixth position of cancer-specific causes of death, topped by lung, liver, stomach, colorectal and oesophageal cancer. These deaths occur almost equally in both, more developed and less developed regions, thus leading to a twofold higher mortality rate in the more developed regions.
2.1. Incidence and mortality trends
Table 2 shows the current incidence and mortality of the USA , Germany [7, 8] and the Munich Cancer Registry . These rates have changed considerably over time. Time series of more developed countries show that the incidence rates experience a drastic rise from 1985 to 1995 and remain at this high level. In the USA incidence (by world standard per 100,000) increases slowly from 1975 until 1985 (from 50 to 65). Then it rises rapidly reaching a peak of 135 in 1992. Then it decreased, since 1995 more slowly, but it remains on a higher level than before the peak (around 110). In Germany incidence is rising continuously since 1988 (from 30 to 75). The main explanation for these trends is the broad use of prostate specific antigen (PSA) testing as a screening method and performing biopsies, which started in the mid-1980s in the USA and in the early 1990s in Germany.
|Incidence ASR (W)||106.1||82.7||76.4|
|Mortality ASR (W)||10.2||11.7||13.3*|
|Median age at diagnosis(years)||67.0||69.5||67.2|
|Median age at death(years)||80.0||76.7|
|5-year overall survival(%)||77.0||79.2|
|5-year relative survival(%)||99.2||92.0||93.4|
|10-year overall survival(%)||58.2|
|10-year relative survival(%)||98.3||87.8|
In the USA, mortality initially increases slightly from 1975 and since 1992 it is decreasing more rapidly (from 14 over 17 to 10). In Germany the mortality rate (by world standard per 100,000) stays stable at 13.
2.2. Age distribution and age-specific incidence and mortality rate
Nearly all patients (≈ 99%) who are diagnosed with prostate cancer have reached an age of fifty or higher. The age distribution at diagnosis describes a positively skewed unimodal distribution with its modus at the age group 65-69. This age group contributes to nearly 25% of all prostate cancer cases. The risk of getting prostate cancer increases nearly exponentially with increasing age. This makes prostate cancer one of the most distinctive cancers in aging populations (Figure 1) with a ASIR of 800-1000 per 100,000 in the elderly of 70 years and older.
Nearly all patients who died of prostate cancer (singular initial malignoma) have reached an age of fifty-five or higher. The distribution of age at death describes a negatively skewed unimodal distribution with its modus at the highest age group 85+. Here the age-specific mortality rates (ASMR) can perfectly be described by an exponential function. The risk of dying by prostate cancer increases accelerated with increasing age (Figure 2). The ASMR reaches 450 per 100,000 for men with an age of 80-84 and already 600 per 100,000 for men older than 84.
3. Prognostic factors
According to Table 3 the conditional age distributions of the combined T categories 2 until 4 have the same shape and the modus at the age group of 65 until 69. These distributions are shifted slightly towards higher ages with the increasing T category. This simply reflects that it takes time to develop an advanced tumour. However, in those patients diagnosed with T1 category (clinically) the age distribution appears to be totally different. Here 80% of the men are older than 64 (about 60% within the other T categories) and every third man is older than 74.
|50 - 54||1.5||4.5||3.5||3.0||3.8|
|55 - 59||3.0||11.0||10.2||11.1||9.8|
|60 - 64||9.7||20.2||18.2||15.1||18.2|
|65 - 69||20.9||31.4||32.8||26.4||30.1|
|70 - 74||26.1||20.2||23.1||19.7||21.7|
|Lymph node status||2.5||1.6||18.4||45.1||7.3|
|PSA value (ng/ml)||25.8||13.2||7.8||3.7||13.2|
|4 - <10||42.0||60.7||41.5||18.9||52.4|
|10 - <20||17.5||18.3||24.9||15.7||19.7|
|2 - 4|
|5 - 6||54.8||48.1||12.3||4.2||39.1|
|8 - 10||11.8||9.8||38.2||68.9||18.7|
Lymph node category (N), distant primary metastases (M), Gleason Score, initial PSA value and Gleason Score are positively correlated with the combined T category: the higher the T category, the higher the PSA value, the higher the Gleason Score and the higher the porportion of regional or distant metastases.
A positive lymph node status is mostly diagnosed when the tumour has spread through the prostatic capsule. Nearly 20% of those men with T3 and almost 50% with T4 tumours therefore are diagnosed with lymph node metastasis.
Although, only 2.4% of all prostate cancer cases have primary distant metastases, already 25% of the T4 patients are diagnosed with metastases.
About 50% of the men with prostate cancer have a PSA value of 4 to 10 ng/ml at initial diagnosis.
According to Figure 3aa shift from capsule exceeding tumours to capsule limited tumours took place in the 1990s. In the late 1980s about 15% of the diagnosed tumours were staged T4, some 45% T3 and nearly 25% T2. In the 2000s only some 5% of the diagnosed tumours were staged T4, good 20% T3 and about 60% T2. The T1 category was unaffected and oscillated around 12% during the whole time period. It seems that PSA-Screening has considerably lowered the proportion of locally advanced tumours.
Table 4 presents in detail the effects of combined T category on the choice of therapy. Guidelines  note that radical prostatectomy, radiation therapy and hormone therapy in combination with radiation therapy are the main primary treatment options when the tumour remains within the prostate capsule (T2) or does not invade nearby structures other than the seminal vesicles or the bladder neck (T3). A spreading prostate cancer should be treated with a hormone therapy. Active surveillance (AS) and watchful waiting (WW) are only noteworthy initial therapy strategies for tumours detected in an early stage. Although these are accepted treatment options in localised prostate cancer, they are seldom chosen compared to radical prostatectomy and hormone therapy. Transurethral resection of the prostate is not an appropriate surgical treatment option in prostate cancer but its proportion in T1 category (46.7%) indicates a greater proportion of incidentally found prostate cancers during a treatment of benign hyperplasia. Without further surgical or hormone therapy, one could classify these cases into the AS or WW groups.
|AS and WW||8.0||0.8||0.7||0.2||1.6|
As Figure 4 shows impressively, initial therapy strategies have changed noticeably over the last 20 years. In the late 1980’s radical prostatectomy was the initial therapy in about 25% of all treatments. Its rate increased continuously and finally reaches almost 60%, making this the most selected initial therapy per year since 1995. The curve of hormone therapy developed oppositely. To be more precise: hormone therapy was the most selected treatment till 1994. From 65% in 1989 it continuously decreased to now 20%. Radiation therapy (XRT) slightly increased to 10% as initial therapy. Finally, within the whole time span transurethral resection of the prostate (TUR) remains stable at a proportion of nearly 10%.
The following figures mainly present the relative survival (RS) curves, an estimator for the cancer specific survival. This is calculated by dividing the overall survival (OS) of the observed cohort by the expected survival of a normal population with the same distribution regarding birth-date and sex.
When looking at the influence of the year of diagnosis on the overall survival (Figure 5) or relative survival (Figure 6) only the curve of patients with a diagnosis in the years 1998 until 1992 noticeably differs from the other ones. Here the 5- and 10-year relative survival was 85.0% and 74.3%, respectively. In the group of patients diagnosed between 1993 and 1997 the 5- and 10-year relative survival was 94.9% and 88.6% in the group of 1998-2002 the 5- and 10-year relative survival was 94.0% and 84.1% and in the recent group of 2003-2008 the 5-year relative survival was 92.1%. Therefore, the following survival analyses are presented for patients with a diagnosis between 1998 - 2008.
The complete cohort of prostate cancer patients with a diagnosis between 1998 and 2008 (Figure 7) shows a 5-year overall survival of 78.8% and a 10-year overall survival of 57.7%. The relative survival is 93.6% and 84.1%, respectively. For comparison: SEER data show a 5-year relative survival of 99.2% for patients diagnosed between 2002 and 2008 and a 10-year relative survival of 98.3% for the cohort of 1998 – 2008.
Figure 8 presents the relative survival by the combined T category. As expected, patients with a T2-staging perform better than patients with a T1-Staging. The 5- and 10-year relative survival is 102.0% and 94.0% in T1, 104.9% and 108.8% in T2, 97.6% and 89.5% in T3 and 61.4% and 43.8% in T4, respectively. Relative survival can exceed 100%, because prostate cancer patients benefit from the better treatment of comorbidities during aftercare.
Lymph node status (N category) is an important prognostic factor. As Figure 9 shows, a positive lymph node status (N+) reduces the relative survival drastically (77.7% for 5-year and 61.9% for 10-year survival) compared to a 5- and 10-year survival of 105.5% and 107.5% in N0. Nonetheless, prostate cancer patients benefit from radical prostatectomy in the situation with lymph node metastases .
According to Figure 10 patients with the worst Gleason Score category (8 – 10) have a much poorer survival (73.4% for five year and 55.0% for ten year survival) than patients with a scoring of 7 and better, which does not discriminate very much (104.1% and 94.8% for Gleason Score 2 - 4, 102.2% and 98.6% for Gleason Score 5 – 6 and 98.6% and 91.8% for Gleason Score 7).
If the tumour has metastasised or locoregional recurrence has occurred, only 18.2% of the patients survive 5 years and 7.2% of the patients survive 10 years. The median survival is about two years (Figure 11).
WHO→World Health Organization
SEER→“Surveillance, Epidemiology and End Results” Program of the National Cancer Institute of the USA
NCHS→National Center for Health Statistics
RKI→Robert Koch Institut
MCR→Munich Cancer Registry
PSA→Prostate specific antigen
HIFU→High-intensity focused ultrasound
TUR→Transurethral resection of the prostate
ASR (W)→Age-standardised rate, using the proposed world standard population of Segi (1960)
ASIR→Age-specific incidence rate
ASMR→Age-specific mortality rate
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National Cancer Institute: “Surveillance, Epidemiology and End Results” (SEER) Program. http://www.seer.cancer.gov.
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National Institute for Health and Clinical Excellence. www.nice.org.uk.
Engel, Bastian et al., Survival benefit of radical prostatectomy in lymph node-positive patients with prostate cancer. Eur Urol 2010; 57(5):754-61.