In general, the age-standardised incidence rates of prostate cancer above the age of 50 years in all three countries increased between 1973 and 2006, and occurred at a faster rate in Sweden and Geneva than in Singapore. The sharper rise occurring in Sweden after the early 1990s is consistent with the increasing availability of PSA testing  and may also be attributed to the more frequent use of transurethral resection of the prostate and invasive diagnostic procedures such as random biopsies . In Singapore, PSA screening is currently recommended for males aged 50 to 75 years and with a first degree relative diagnosed before age 65 years , whereas approximately 1 in 2 males above age 50 years in Sweden (56 % in 2007 ) and Geneva (55 % in 2005 ) had PSA screening. This could explain the sharper rises in incidence rates after 1993 in Sweden and Switzerland compared to Singapore. It is possible that the continuous rise in incidence rates in Singapore may represent a real increment of incident cases, given the highly selective criteria for screening. A further potential risk factor for these increasing incidence rates in Singapore could be due to the adoption of a more Westernized diet that generally has a higher intake of animal fats . In comparison, soy based Asian diets have been shown to provide some protection against prostate cancer [30, 31].
As the upper limit for screening in Singapore , Sweden  and Geneva  is up to 75 years, it is expected that the rate of increase in incidence in the 75+ year age group is slower (Figure 2). The higher overall age-specific incidence rates for Geneva and Sweden may be explained by the higher baseline incidence and higher screening rates . In addition, rapidly aging populations in the three countries will have a growing number of men reaching an older age which may contribute to the disease becoming more frequently diagnosed .
The age-standardised mortality rates declined in the later periods for all three countries. From our results, mortality rates for Geneva declined steadily from 1973 onwards whereas for Singapore there was a steady rise in mortality rates from 1968 to 1992 with a recent decline from 1993 onwards. This raises the question of whether this could be an effect of PSA testing. To date there is little conclusive evidence that PSA-based screening reduces prostate cancer mortality. However, recent randomised controlled trials have shown contradicting results. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial in the US showed a marginal increase in the incidence and concluded that there was no mortality reduction with combined PSA and digital rectal examination screening over an 11 year median follow-up . The UK based European Randomised Study of Screening for Prostate Cancer (ERSPC) trial after a median follow-up of 11 years showed an increased incidence and a 21% relative reduction in risk of death that was only marginally statistically significant at p = 0.001 .
Treatment of prostate cancer does not differ greatly between the three countries yet the mortality rate is declining much faster in Singapore and Geneva compared to Sweden. It is uncertain whether this observation can be explained by genetic differences in the populations, different environmental factors or a combination of both (gene-environment interactions) . Alternatively, it may argued that the drop in mortality is due to technological advancements in diagnosis and treatment of the disease, such as newer surgical approaches for localized disease, improved irradiation techniques and hormonal/antiandrogenic therapy , or due to a combination of all these factors. The relatively sharper drop in mortality rate in Geneva may be due to the adoption of hormonal therapy .
From the APC modeling, the incidence and mortality rates of prostate cancer appeared to be more strongly associated with the age and period effect than with the birth-cohort effect in all three countries, based on the lower calculated AIC criteria and likelihood ratio test results. Older males tended to be at higher risk of developing prostate cancer and in the later periods. In addition, mortality was higher in older males and across the earlier periods, which could be confounded by PSA testing. Males of older age and in the later period of diagnosis had a higher incidence, whereas males of older age and in the earlier period had higher mortality rates for prostate cancer.
A limitation of this study was that it extended over a relatively long time period during which changes in diet, environmental and diagnostic factors are likely to have occurred. It would be a further challenge to identify the independent factors influencing the change in the trends of incidence and mortality as it could be due to individual factors acting independently or in combination. Age-standardized rates for incidence and mortality in our study are not comparable with other published data as different weightings were used. Accurate interpretation of the incidence and mortality trends in the three countries would be incomplete without data on PSA screening as a potential confounder. As data on individual PSA testing was not available, it was not possible to separate the effect of the real increment in incident cases from over-diagnosis due to increased screening, as we would need to establish whether patients had PSA screening prior to diagnosis.