Because the incidence of prostate cancer (PCa) in Korea currently is led by its spread among the elderly population, it is projected to increase significantly in parallel with the accelerating trend of societal aging,^1,2 In the detection of PCa, serum prostate-specific antigen (PSA) testing plays a pivotal role, given that the majority of contemporary PCa does not manifest any specific symptoms besides ambiguous male lower urinary tract symptoms that originated more frequently from the concomitant benign prostate hyperplasia. Therefore, the most serious consequence of current Western-based prohibitive guidelines on the PSA test, particularly for the elderly in Korea, is that their negative impact on the establishment of screening policy for the men who may benefit from the PSA test, given this distinctive epidemiologic background on the PCa.

As with other Asian countries,³ the incidence of PCa in Korea is rapidly increasing in the last decade. Since 2002, when PCa was firstly reported as the 5th most commonly developing male malignant disease, the incidence of PCa has kept increasing jumping one spot to the 4th from 2016. In the most updated report (2019), PCa became the 3rd prevalent cancer among the Korean male, and 2nd most common cancer especially in the aged men over 65 years old,⁴ despite a limited social awareness dominantly caused by the absence of a nation-driven public screening policy influenced by contemporary western recommendations.

Given the age-related increasing incidence of PCa along with the national-wide trend of aging which has been manifested more remarkably in a rural than an urban area, we traced the incidence of serum PSA testing by the residential areas of Korea and investigated its impact on the detection of PCa.

The ultimate aim of a population-based screening strategy is to promote cancer-specific survival. About the benefit from the mass screening policy based on PSA, however, there is still controversy particularly since 2012,^6,7 when the US Preventive Study Task Force (USPSTF) recommended the ban of PSA screening for the mass population mainly due to the lack of positive evidence on the prolonging the survival by applying it to the screening, rather generating overdiagnosis and overtreatment on so-called an insignificant disease.⁸ Even though USPSTF modified their original recommendations in 2018, opening slots of PSA screening for the explained individuals aged between 55 to 69 years,⁹ the macroscopic consequence of accepting a specific screening strategy can be quite different in each country, based on the exposure rate to the PSA testing and manifestation of racial differences in PCa incidence. In this point, how the contemporary Western guidelines on PSA screening that are strongly affected by the statements from the USPSTF apply to Korean males' remains unclear, when one considers the lack of data on the frequency of PSA testing and distinctive difference in the proportion of the aged population among the newly diagnosed PCa in Korea.

Nowadays, the majority of PCa was found in the non-metastatic stage, mainly due to the enhanced public awareness of the prostatic disease that often develops in the aging male, along with the increased detection by PSA testing. As a result, the incidence of PCa in Korea increased dramatically, more than 12 times just within a couple of decades by the most updated national-wide cancer registry (1,258 in 2000 vs. 14,857 in 2018), even in the absence of a regular check-up policy on PCa in contrast to other prevalent malignant diseases such as lung, stomach, colon, and liver cancer, that currently is the 1st, 2nd, and 5th prevalent male cancer in Korea.⁴ As with other Asian countries, the peculiar characteristic in the epidemiologic feature of PCa is that it primarily encroaches on the elderly with age-related increasing incidence rates.^1,2 Therefore, considering the prominent trend of social again in the rural area than urban or metropolitan counterparts, we are going to contrast the incidence of PSA across these residential areas from this study.

Several interesting findings that deserve to be emphasized were observed from this study. First, the investigated PSA incidence of 7.27% among those aged over 40 years from this study shown in Table 1 was significantly lower than that from other countries. In a PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) study carried out in the US, they reported that over 90% of men in the ‘usual care' arm underwent some degree of PSA testing in 2009.⁶ In 2005, it has been reported that about 40% of those aged over 50 years in the US had at least one PSA test in the prior year.¹⁰ A Japanese hospital-based cohort study reported that 73.5% of PCa patients aged 55-69 years were detected by PSA screening in 2014,¹¹ but in Korea, about a quarter of diagnosed PCa had repeated PSA test before the diagnosis in the recent decade.¹²

Second, despite a similarly increasing exposure rate to the PSA test across all residential areas among the Korean male, the repeated screening opportunity was focused on the inhabitant of a metropolitan area. The value of a single session of PSA test as a screening modality has been investigated by several recent trials, but they con-sistently failed to demonstrate a similar clinical relevance as serial check-ups had.^13,14 Thus, the ideal screening strategy has to be designed to provide serial check-ups by repeated PSA tests. From this point of view, the relatively lower interval of repeated test of rural area (2.83 times on average during 11 years) in comparison to the inhabitant of a metropolitan area (3.25 times in Seoul, 2.97 times on average from metropolitan area) deserves to be addressed. Given the maintained trend of the highest incidence of PCa in a rural area than the other areas, this disparity by the residential area should be reconsidered from the viewpoint of equality, in the accessibility of medical services.

The authors are well aware of the limitations of this study. First, the current version of the Korean NHIS data does not provide basic information on risk stratification of PCa, including the serum level of PSA, clinical stage, and Gleason score or grade. Thus, we cannot identify the significant disease among the indolent PCa in this analysis. While the majority of randomized clinical trials on the efficacy of the PSA test as a screening tool for PCa demonstrated a significant decrease in the incidence of advanced disease, which reflects the probability of low-risk PCa dominantly screened by this strategy.¹⁵ However, concerns over the overdiagnosis and overtreatment of insignificant PCa should be weighted with the concerns on consistently reported aggressive nature of disease among the Korean males.^16-18 Second, because the current version of NHIS did not allow to capture the patients who previously had PSA testing perfor-med through a private, noninsured health check-up, some of the nonscreened groups in this study may have proper PSA screening in the real world. The number of those with PSA testing by the private sector was unknown due to the absence of a national-wide counting system. However, given the current reported average retirement age of 51.2 years from their longest employment among the Korean male in 2021¹⁹ and the elderly-driven prevalence PCa in Korea as shown in Table 3, the omission of these private PSA testing data is unlikely to have substantially affected our results, especially for the inhalant of rural area. Third, although associations between the residential area, the mean age, the incidence of PSA and PCa were identified from this study, a causal relationship was not clear from the observational study design. Furthermore, the variables which allow being investigated by the current version of NHIS look superficial to extract a solid conclusion. Thus, these results should be considered as hypothesis-generating and will spur further investigations into PSA screening in societies with limited social awareness of the disease.

Despite a recent increase of PSA screening and diagnosis of PCa especially in the rural area driven by a larger proportion of the aged population, the opportunity of repeated testing was presented more frequently to the inhabitant of a metropolitan area. Given the relatively low exposure rate to the PSA test regardless of the residential areas in general and the uneven nature of PSA testing by the lack of screening, these outcomes propose the clinical relevance for the establishment of countrywide policy which enables expanding the implementation of PSA testing, in a country with rapidly growing PCa incidence.