Opportunistic prostate cancer screening: A population-based analysis

ARTICLE IN PRESS

Urologic Oncology: Seminars and Original Investigations 000 (2019) 1−8

Clinical-Prostate cancer

Opportunistic prostate cancer screening: A population-based analysis Bashar Matti, M.B.Ch.B.*, Kamran Zargar-Shoshtari, M.B.Ch.B., M.D., F.R.A.C.S. (Urology) Department of Surgery, University of Auckland, Auckland, New Zealand Received 12 September 2019; received in revised form 12 November 2019; accepted 2 December 2019

Abstract Background: Prostate specific antigen (PSA) utilization in population-based prostate cancer (CaP) screening, has been a controversial area for decades. Current recommendation in our region is for an opportunistic approach to screening, with estimated low prevalence of such practice in the community. However, our clinical observations suggested that the extent is beyond what might be expected from an opportunistic screening practice. This study aims to estimate the current prevalence and the extent of opportunistic CaP screening, and investigate the contemporary patterns of PSA testing in a large population. Methods: From 2008 to 2017, all men in the Northern cancer network of New Zealand, who had a screening PSA test performed in a community laboratory were identified. The study variables were accessed from multiple prospectively maintained databases. These included: Age, Ethnicity, Region, Social deprivation, Medical therapy, CaP history, Gleason score, and PSA test information (results and date). Population estimations were obtained from customized an updated national census data. Results: The study cohort constituted 311,725 men, with 1,208,214 PSA tests performed, in the ten-year period. The mean age at first test was 55.2 years and each man received approximately 4 PSA tests. The prevalence of opportunistic CaP PSA screening in men aged 40 to 79 years, was 87% of the region population. In the 50 to 69-year age group, 65% of men in the region had been receiving regular 2-yearly, screening PSA tests. Men who had 3 or more PSA tests, were more likely to be diagnosed with CaP (Odds ratio [OR] 1.85, P < 0.001). Conclusions: PSA based CaP screening, is a highly prevalent practice in the NZ community. This raises concerns regarding the quality of the individual counseling process and the adequacy of resources allocated to accommodate for such practice. Ó 2019 Elsevier Inc. All rights reserved.

Keywords: Prostate specific antigen; Prostate cancer; Population screening

1. Introduction The concept of population-based screening for early detection of cancer has been well implemented in clinical practice for malignancies such as breast, cervical, and colorectal cancers [1]. However, despite 3 large randomized clinical trials which included over 500,000 men, prostate specific antigen (PSA) based screening for prostate cancer (CaP), remains controversial [2]. Even with long-term data supporting improved cancer-specific mortality with PSA testing, the balance between the effectiveness, overdiagnosis, overtreatment Funding: This work was supported by the University of Auckland; the Goodfellow foundation for urology research; and the Auckland Medical Research Foundation. *Corresponding author. Tel.: +64 9 373 7599; fax: +64 9 377 9656. E-mail address: [email protected] (B. Matti). https://doi.org/10.1016/j.urolonc.2019.12.009 1078-1439/Ó 2019 Elsevier Inc. All rights reserved.

and benefit to harm ratio, remains a major source of debate. The European Randomised Study of Screening for Pca (ERSPC) demonstrated that at almost 20 years of follow-up, the number of men needed to be screened and diagnosed to prevent one CaP death were 101 and 13, respectively [3]. These are in fact lower than those seen for breast and colon cancer screening [4]. On the other hand, PSA based screening may lead to over detection (and potentially treatment) of 7 more CaP, per 1,000 men screened [2]. Currently, there are no standard consensus with regards to the utility of PSA for CaP screening [5]. A number of organizations and professional societies, have issued guidelines against PSA screening [6-8]. Others, such as the American Urological Association (AUA), the American College of Physicians (ACP), the National Comprehensive Cancer Network (NCCN), and the 2018 statement from the

ARTICLE IN PRESS 2

B. Matti and K. Zargar-Shoshtari / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−8

US Preventive Services Task Force, have recommended shared decision making [5,9,10]. The European Association of Urology (EAU) have previously recommended an individualized risk-adapted early strategy with baseline PSA test at the age of 45 to 50 years in well-informed men with life expectancy of more than 10 years [11]. EAU’s latest position statement recommends organized, populationbased PSA screening [12]. A formal population-based CaP screening program does not exist in our region [13]. Current regional guidelines suggest offering 1- or 2-yearly PSA testing for healthy, wellinformed men aged 40 to 70 years. It had been postulated that these guidelines, would lead to screening PSA testing in approximately 20% of men aged 50 or above [14]. However, in our population, PSA testing is readily available without cost to all patients and can be ordered by any clinician without restrictions and based on our clinical observations, we believe the prevalence of PSA testing to be significantly higher. We hypothesize that secondary to the ease of access and general regional attitudes for regular “health checks,” opportunistic PSA testing will be highly prevalent in our population. This carries unforeseen consequences on patients, resources and the delivery of health care services. This study aims to assess the frequency and prevalence of opportunistic PSA screening in a large population of men in our region and to evaluate the efficacy of the community-based PSA testing process.

2.2. PSA data

2. Materials and methods

This is retrospectively assessed by identifying the proportion (fraction) of men who had at least 1 PSA test in our region, within the study period. The number of men with qualified PSA tests (the numerator) were divided by the total male population estimates in the region (the denominator). The latter were specifically provided to our research team by Statistics NZ, and were custom analyses based on national census (2006 and 2013), with account to population growth estimates. The age-matched count of men known to have CaP prior to the study commencement was removed from the denominator.

2.1. Population data The data were collected from New Zealand’s Northern regional cancer network, containing a population of 1,851,450 residents, including 911,770 (49%) men with 377,020 (41%) being 40 years or older [15]. This region includes four major hospital systems (District Health Boards) and accounts for approximately 38% of the total population of the country. In 2013, the ethnic distribution of men in this region was: 51% European or other, 24% Asians, 13% indigenous (Maori), and 12% Pacific Islanders. Three prospectively maintained databases were linked together to generate the study population. This was only possible since New Zealand (NZ) has a unique single identifier assigned by the Ministry of Health to each health user, known as National Health Index (NHI). First dataset included all laboratory, pathology, radiology, and pharmaceutical dispensing records, which were extracted through an electronic system called E-Clair (Sysmex, Auckland, NZ) [16]. Second dataset included the demographic information stored in each NHI number (date of birth, date of death, ethnicity, and deprivation index). Third dataset was the NZ cancer registry, which maintains detailed information on the incidence and characteristics of every CaP diagnosed in the country from 1,948 onwards.

From January 2008 to December 2017, the result for every PSA test performed in our region was extracted into the study database. Since we targeted PSA testing for screening purposes, men known to have CaP prior to the study commencement, were excluded. Similarly, PSA tests for men who developed CaP within the study period, were included until the date of cancer diagnosis. We matched NHI identifiers to cancer registry data in order to identify and exclude known CaP men from the study database. In addition, data on men receiving treatment for lower urinary tract symptoms (LUTs), including alpha blockers and/or 5-alpha reductase inhibitors, were collected. This was performed in order to compare PSA testing patterns in symptomatic and asymptomatic men, to test the effect of LUTs on the screening process. For this part of the analysis, PSA tests performed prior to commencement of medical therapy, were excluded. Data collected included age, ethnicity, socioeconomic status (SES), frequency of testing (number of PSA tests per person over the ten years period), the date of PSA test, PSA value, medication dispensing records, prostate biopsy outcomes, and cancer related information. The data were stored in a central project database. 2.3. Primary outcomes 2.3.1. Prevalence of opportunistic screening

2.3.2. Prevalence of regular PSA testing For the purpose of this study, regular PSA testing was defined as obtaining 2 or more PSA tests, at a minimum of 2 years interval. This interval was selected based on the previous CaP screening trials, and the AUA, EAU, and local screening guidelines [3,9,11,13]. The prevalence was estimated for men aged 40 years or older, in the same method described in section 2.3.1. 2.4. Secondary outcomes: efficacy of population sampling and community-based PSA testing For this part of the analysis, men aged 50 to 69 at the time of first PSA test, were considered. This group represents the

ARTICLE IN PRESS B. Matti and K. Zargar-Shoshtari / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−8

“target” age for CaP screening as recommended by the regional and international guidelines. We hypothesized that if opportunistic screening was in a perfect system, then all men in this group, irrespective of demographic backgrounds, should have similar access to PSA testing. We examined the effect of SES, age, and ethnicity on the PSA testing frequency, and subsequently on CaP detection rates. 2.5. Statistical analysis Statistical analysis and data management was conducted using SPSS 25.0. Descriptive statistics were listed either in crude numbers, proportions, or as mean (standard deviation and/or interquartile range). Primary outcomes were reported in percentages over 5-year age intervals, with age at first PSA test within the study period used for each numerator. Secondary outcomes were reported as adjusted and unadjusted odds ratio (OR). Pearson correlation (r) used to estimate linear correlation between variables. Univariate, multivariate, and binary logistic regression analysis performed for adjustments and comparisons when appropriate. Estimated mean, differences, and OR reported with 95% Confidence Intervals (CI). For all calculations, a P value < 0.05 was considered statistically significant. 2.6. Ethical approval Ethics approval for human participation in this study, has been obtained from the relevant institutions and the Health and Disability national ethics committee (HDEC). 3. Results

3

commencement and were excluded from the “screening” study. Therefore, 311,725 men were included in the final analysis. The ethnic distributions in this PSA tested cohort were as follows: 65% European or Others, 15% Asians, 13% Maori and Pacific Islanders and 7% unknown. Over the 10 years study period, the frequency of PSA testing for the entire cohort was 3.9 (3.6, 4) tests per person. Mean age at first test was 55.2 years (12.3, 17). On average, the number of men in the cohort receiving PSA tests increased by 5% per year. Table 1 shows the cohort’s characteristics listed for each year of the study period. The frequency of PSA testing increased with age at first test, and peaked at 71 years (r = 0.24, P < 0.001). The average frequency of PSA testing, was 2.9 (2.4, 3), 4.1 (3.5, 4), 5.2 (4.4, 5), 4.9 (4.7, 5), and 3.6 (4.2, 3) tests per person, for men aged 40 to 49, 50 to 59, 60 to 69, 70 to 79, and 80 to 89 years, respectively. Within the entire cohort, 70.1% of men (n = 218,594) received 2 or more PSA tests (Table 2). Those men were generally older compared to participants who had a single test (56.7 vs. 51.5 years, P < 0.001). Furthermore, the time difference between first and last PSA tests, increased significantly with the number of tests per person performed (r = 0.58, P < 0.001). The proportions of men in the region, who had at least 1 PSA test in the study timeframe, is illustrated in Fig. 1. The prevalence of opportunistic screening was highest in the sixth decade of life, with nearly 100% of the population being tested. Similarly, 87% of men aged 40 to 79 had received at least a single screening PSA test in the 10-year study period. The PSA testing prevalence remained high for men aged 80 years or above (63%).

3.1. Opportunistic screening in the cohort 3.2. Regular PSA testing patterns From January 2008 to December 2017, 1,485,721 PSA tests were performed in 320,520 men. About 8,795 men (2.7%) had confirmed diagnosis of CaP at the time of study

Fifty-eight percent of the entire cohort met our defined criteria for regular PSA testing. These men had 1,011,416

Table 1 Characteristics of men who received PSA testing in the Northern Cancer Region of New Zealand, from 2008 to 2017. Study year

No. Men tested

Age a

No. PSA tests

No. PSA tests per person b

No. Men with first PSA test

Age c

2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Total

74,165 78,210 88,454 89,661 99,229 111,868 112,724 115,680 115,968 117,987

59.4 (11.7) 59.4 (11.7) 59.2 (11.7) 59.5 (11.7) 59.7 (11.7) 59.7 (11.6) 60.0 (11.6) 60.2 (11.5) 60.4 (11.5) 60.7 (11.5)

89,509 94,897 105,661 107,517 118,768 134,793 135,113 138,985 139,692 143,279 1,208,214

1.21 1.21 1.19 1.19 1.20 1.19 1.20 1.20 1.20 1.21 1.20

74,165 43,386 34,888 25,480 27,239 29,211 22,830 20,016 17,816 16,694 311,725

59.4 (11.7) 56.5 (11.8) 54.8 (12.1) 53.6 (12.2) 54.2 (12.5) 54.1 (12.3) 52.3 (12.1) 51.9 (12.1) 51.4 (12.0) 51.1 (11.9) 55.2 (12.3)

a

Mean age (SD) in years. Mean. c Mean age (SD) in years. Note the decline indicating PSA testing in younger men. b

ARTICLE IN PRESS B. Matti and K. Zargar-Shoshtari / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−8

4

Table 2 Characteristics of men who received PSA testing in the Northern Cancer Region of New Zealand, from 2008 to 2017, grouped by the number of PSA tests. No. PSA tests

No. Men

Percent of total

Age at first test a

Age at last test a

Years between first and last tests b

1 2 3 4 5 6+

93,131 54,478 38,985 29,535 23,188 72,408

29.9 17.5 12.5 9.5 7.4 23.2

51.5 (13.6) 54.0 (12.4) 55.4 (11.8) 56.2 (11.2) 57.0 (10.7) 59.5 (9.9)

51.5 (13.6) 56.7 (12.2) 59.6 (11.5) 61.5 (10.9) 63.1 (10.4) 67.0 (9.8)

N/A 2.57 (2.55−2.58) 4.17 (4.15−4.19) 5.29 (5.27−5.31) 6.11 (6.09−6.14) 7.59 (7.57−7.60)

a b

Mean age (SD) in years. Univariate analysis where age at first test was a covariate.

Fig. 1. Proportions of men in the Northern Cancer Region of New Zealand, who had at least 1 PSA test for opportunistic CaP screening, plotted against 5year age intervals.

PSA tests performed with a mean of 5.7 tests per person (3.9, 4). The mean age at first test in this “regular screening cohort” was 57.2 years (10.4, 15). The average time interval between first and last tests was 6.1 years (2.2, 4). Fig. 2 illustrates the prevalence of screening in this group. Overall, 65% of men aged 50 to 69 years in the region, received regular PSA testing.

3.3. PSA testing in symptomatic men We identified 40,987 men who received treatment for LUTs within our study period. This group underwent 273,150 PSA tests. Forty four percent (n = 122,061) of these tests were performed prior to commencement of treatment

Fig. 2. Proportions of men, aged 40 or above, in the Northern Cancer Region of New Zealand, who had regular screening PSA tests for CaP, plotted against 5-year age intervals.

ARTICLE IN PRESS B. Matti and K. Zargar-Shoshtari / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−8

5

Table 3 Characteristics of men who received PSA testing in the Northern Cancer Region of New Zealand, from 2008 to 2017, Grouped by presence and absence of LUTs. Variable

No. Men (%) No. Men with repeated PSA test (%) No. PSA tests Age at first test in years (mean, SD) PSA tests per person (mean, SD)

Men with LUTs

40,987 (13.1) 29,230 (71.3) 151,089 65.9, 11.8 3.7, 3.4

Men without LUTs

270,738 (86.9) 180,992 (66.9) 934,514 54.1, 12.1 3.5, 3.2

for LUTs and may have not been as part of “symptomatic screening” and hence, were excluded. Majority of these men (93.5%) received alpha blockers while 6.5% received finasteride. Table 3 demonstrates the characteristics in men with and without symptoms. Symptomatic men were generally older, and were more likely to receive a repeated PSA test (unadjusted OR 1.23, 95% CI 1.21−1.26, P < 0.001). Multivariate analysis including PSA testing frequency, age, and symptoms presence, showed that men with LUTs have marginally higher testing frequency compared to asymptomatic men (mean difference 0.24, 95% CI 0.20−0.27 tests per person, P < 0.001). 3.4. Efficacy of population sampling Fifty two percent (n = 160,827 men) of the total cohort were in the “target” age group (50−69 years) at the time of first PSA test. Majority (62%) of these men had 3 or more PSA tests, while the remainder (n = 61,470 men) had 1 or 2 tests. Within this sub-cohort, 5,425 (3.4%) men were diagnosed with CaP and majority of these cancers were detected in men in the higher testing frequency group (74.5% vs. 25.5%, P < 0.001). This corresponds to unadjusted OR of 1.85 (95% CI 1.74−1.96, P < 0.001). Significant differences were observed in socioeconomic and ethnic characteristics between the 2 groups (Table 4). Men in the high frequency group were more likely to be living in a better socioeconomic area (adjusted OR 1.45, 95% CI 1.42−1.48, P < 0.001), and to be of non-Maori, non-Pacific Islander ethnicity (adjusted OR 2.03, 95% CI 1.96−2.03, P < 0.001). Similarly, younger men and those living in lower socioeconomic areas, were less likely to be diagnosed with CaP (P < 0.001). 4. Discussion This study is one of the largest population-based projects, which has examined “the real world” utilization of opportunistic CaP screening, within a healthcare setting where PSA tests are freely and easily accessible for all health practitioners. We have demonstrated that, despite controversies and limitations associated with PSA testing, a high intensity of opportunistic screening is in existence. In

Multivariate analysis Mean difference (95% CI)

t statistic

P value

N/A N/A N/A 11.8 (11.72−11.99) 0.24 (0.20−0.27)

N/A N/A N/A 186.03 13.86

N/A N/A N/A < 0.001 < 0.001

this study, over a ten-year period, each man received an average of 3.9 PSA tests. The age at which PSA testing commenced (55 years), was in line with the AUA and EAU recommendations [9,11]. In addition, we observed a relatively low prevalence of PSA usage in men younger than 40 years. However, the high prevalence of screening in elderly men, aged 80 or above, was surprising. A potential explanation for this trend, is the true opportunistic nature of this approach, offering PSA tests for men seeking medical care for nonurological reasons. Moreover, older men are more likely to develop symptoms which may trigger PSA testing in the primary care setting [17,18]. Another possible contributor is a degree of reluctance from clinicians to stop cancer screening in older men [19]. All of these possible reasons in turn, highlight the known pitfalls of a non-structured approach to health screening. Our study revealed that the “real-world” prevalence of PSA testing is significantly higher than previously estimated in our region (87% vs. 20%). This observed prevalence of PSA testing was comparable to Sweden, but higher than the United Kingdom (UK). In a study of PSA testing in Stockholm County, from 2003 to 2011, Nordstrom et al demonstrated that approximately 60% of Swedish men, aged 50 to 79, received at least 1 PSA test [20]. Furthermore, the authors reported that the incidence of re-testing to be 40%, 51%, and 58%, for men in their 50s, 60s, and 70s, respectively. These figures are similar to our observations, and correspond to similar cancer incidence in the 2 regions (Age-Standardized Rate of 100.7 and 99.4 cancers diagnosed per 100,000 men, in Sweden and NZ respectively [2011 estimates]) [21,22]. On the other hand, the estimated 10-year risk of exposure to a PSA test in the UK, for men aged 45 to 69, is 39.2% [23] with estimated incidence of receiving a follow-up PSA test of 20%. The lower rates of PSA testing is reflected in the incidence of CaP diagnosis, being considerably lower in the UK (Age-Standardized Rate of 72.5 cancers diagnosed per 100,000 men [2011 estimates]) [24]. The implied relation between PSA testing, and CaP diagnosis, is well documented in the literature [5]. In fact, the risk of overdiagnosis is one of the major limiting steps towards implementing the use of PSA testing in an organized population-based screening program [5-11].

ARTICLE IN PRESS 0.720 1.02 (0.93−1.11) < 0.001 1.17 (1.08−1.23) High testing frequency defined as having 3 or more PSA tests within the study period. Binary logistic regression model including variables from all 3 categories. b

Ethnicity

SES

a

2.03 (1.96−2.08) < 0.001 2.36 (2.29−2.43)

< 0.001

1 2.46 (2.33−2.61) 1 1.24 (1.16−1.31) 1 ref < 0.001 ref < 0.001 ref 1 2.47 (2.33−2.61) 1 1.20 (1.14−1.23) 1 ref < 0.001 ref < 0.001 ref 1 1.46 (1.43−1.49) 1 1.45 (1.42−1.48) 1 ref < 0.001 ref < 0.001 ref

50−59 60−69 Low High Maori and Pacific Islanders Others Age at first test

1 1.46 (1.43−1.49) 1 1.63 (1.59−1.66) 1

P value Adjusted OR (95% CI) b P value Unadjusted OR (95% CI)

P value

Adjusted OR (95% CI)b

P value

Unadjusted OR (95% CI)

OR for CaP detection OR for high PSA testing frequency a Variable Category

Table 4 The efficacy of population sampling for PSA testing and prostate cancer detection, for men aged 50−69 years, in the Northern Cancer Region of New Zealand, from 2008 to 2017.

ref < 0.001 ref < 0.001 ref

B. Matti and K. Zargar-Shoshtari / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−8

6

Screening is occasionally defined as testing in asymptomatic men, and therefore we assessed utilization of medical therapy for LUTS as a surrogate for symptomatic presentations. Previous reports of PSA testing in General Practice, have shown that 70% of these tests were performed in asymptomatic men [14,25]. In our cohort, 86% of men receiving PSA testing were asymptomatic. Our higher prevalence is potentially confounded by the fact that we did not assess other possible symptoms, and some men with LUTs might have opted against medical therapy. Nevertheless, we demonstrated that symptoms’ presence led to a marginal increase in the testing frequency (by 0.24 tests per person). This trend, and the commonness of testing in elderly men, maybe explained by the health providers becoming more concerned about CaP, in men with LUTs, despite the uncertainty in literature to support such concerns [26]. In our region, we do not have an organized CaP screening program. However, we do have centrally sponsored national screening programs for cervical and breast cancers [27]. Our study demonstrated that 65% of our “target” population received regular CaP screening PSA tests, which is similar to the well-organized and centrally funded Breast and Cervical cancer screening programmes (70% and 80% respectively), and the newly introduced national bowel cancer screening, which has an anticipated uptake rate of 62%. These comparable proportions reflect the accessibility and ease of PSA testing; however, they do not reflect the cost associated with over utilization of these tests, or the population sampling bias associated with current practices. Opportunistic screening for CaP, has significantly worse mortality outcomes when compared to organized screening [28]. Our study demonstrated that opportunistic community-based screening resulted in significant sampling bias. We observed that men from higher socioeconomic areas were more likely to receive frequent PSA testing, and subsequently, would have higher cancer detection rates. Low intensity testing was observed in 38% of the target cohort. This is more likely to lead to overdiagnosis of low-risk cancer but have no impact on improved CaP mortality rates [29]. Previous studies have reported similar inequalities when using opportunistic approach to CaP screening [30,31]. In the Finnish cohorts of the ERSPC, men with high SES in the control arm, were more likely to be active in the screening process, which had led to lower incidence of advanced and incurable cancers, when compared to those from lower SES [30]. On the other hand, organized screening, as represented in the screening arm of the study, had significantly reduced the disparity in the advanced cancer detection rates. Furthermore, in the Swedish cohort of the ERSPC, the screening arm had significantly lower socioeconomic disparities in CaP specific mortality, when compared to the control arm [31]. This suggests that organized screening for CaP, offer the additional advantage of reducing healthcare disparities in the population. With extensive PSA testing practice in the community, a concern must be raised regarding the adequacy of counseling

ARTICLE IN PRESS B. Matti and K. Zargar-Shoshtari / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−8

offered to men prior the testing process. Most guidelines, including our regional recommendations, emphasize that PSA testing should only be offered following a culturally appropriate discussion with the patient, regarding the benefits and harms of CaP screening [6,9-11,13]. Previous reports, from USA, UK and Australia, have demonstrated the dearth of the consenting process prior to PSA testing [32-34]. In a survey of American men tested in the previous 3 months, Federman et al found that approximately 70% of them, did not have a risk discussion with their primary care provider regarding PSA testing [32]. Likewise, it was found that nearly two-thirds of men referred to a urology clinic in the UK, for elevated PSA results, were not even aware that they had a PSA test done [33]. In a similar settings study from Australia, only 6/48 men were adequately counseled prior to receiving a PSA test [34]. We suspect similar issues with PSA testing of patients in our study. This study offers many strengths. Due to the unique nature of our health system where a single identifier is assigned to each patient, we were able to accurately access and link data from multiple prospectively maintained databases. We utilized the laboratory PSA database which captures every single PSA test performed in the region, essentially eliminating selection bias. Moreover, we accessed the prospectively maintained National Cancer Registry, to ensure the exclusion of PSA tests from men known to have cancer. There are, however, potential limitations to the study data. It is difficult to ascertain the indications of PSA testing in our study populations. Although, we assessed LUTs with utilization of medical therapy, we did not assess other possible symptoms such as urinary tract infection, hematuria or other possibilities. Therefore we cannot be sure whether PSA testing for the remainder of the population was performed in otherwise asymptomatic men for CaP screening purpose. In addition, we did not assess the patterns of secondary referrals following PSA testing in this study, however this is an aim for a secondary project being currently conducted. 5. Conclusions We demonstrated that, there is a high prevalence of opportunistic CaP screening, for men aged 40 years and above. This raises concerns regarding the quality of the individual counseling process and the adequacy of resources allocated to accommodate for such practice. The lack of monitoring on the process had led to a significant sampling bias in PSA testing within the population, which contributed to disparities in cancer detection rates. These observed deficiencies in this opportunistic screening process highlight the potential benefits of a more organized approach, as per the recent EAU position statement on CaP screening. However, this constantly needs to be weighed against the known risks of harms from the PSA based screening process.

7

References [1] American Cancer Society. Cancer prevention & early detection facts & figures 2019-2020. Atlanta: American Cancer Society; 2019. [2] Ilic D, Djulbegovic M, Jung JH, et al. Prostate cancer screening with prostate-specific antigen (PSA) test: A systematic review and metaanalysis. BMJ 2018;362:k3519. [3] Osses DF, Remmers S, Schroder FH, van der Kwast T, Roobol MJ. Results of prostate cancer screening in a unique cohort at 19 yr of follow-up. Eur Urol 2019;75(3):374–7. [4] Richardson A. Screening and the number needed to treat. J Med Screen 2001;8(3):125–7. [5] Kim EH, Andriole GL. Prostate-specific antigen-based screening: Controversy and guidelines. Bmc Med 2015;13. [6] Bell N, Gorber SC, Shane A, et al. Recommendations on screening for prostate cancer with the prostate-specific antigen test. Can Med Assoc J 2014;186(16):1225–34. [7] Livingston CJ, Freeman RJ, Mohammad A, et al. Choosing wisely (R) in preventive medicine the American College of Preventive Medicine’s top 5 list of recommendations. Am J Prev Med 2016;51(1):141–9. [8] American Academy of Family Physicians. Summary of recommendations for clinical preventive services. AAFP; July 2017. [9] Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. J Urol 2013;190(2):419–26. [10] USPST, Grossman DC, Curry SJ, et al. Screening for prostate cancer: US preventive services task force recommendation statement. JAMA 2018;319(18):1901–13. [11] Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 2017;71(4):618–29. [12] Gandaglia G, Albers P, Abrahamsson PA, et al. Structured populationbased prostate-specific antigen screening for prostate cancer: The European Association of Urology position in 2019. Eur Urol 2019. [13] Prostate Cancer Working Group and Ministry of Health. Prostate cancer management and referral guidance. Wellington: Ministry of Health; September 2015. [14] National Screening Advisory Committee. Prevalence of opportunistic prostate cancer screening in New Zealand. Wellington: Ministry of Health; October 2010A report for the National Screening Advisory Committee, Ministry of Health. [15] Statistics New Zealand. 2013 Census usually resident population counts. Statistics New Zealand; October 2013. [16] Sysmex New Zealand Limited. Eclair case study. northern region CDR. 2019. https://www.sysmex.co.nz/solutions/health-it-solutions/ eclair-2/clinical-data-repository/. Accessed April 01, 2019. [17] Haidinger G, Temml C, Schatzl G, et al. Risk factors for lower urinary tract symptoms in elderly men. For the Prostate Study Group of the Austrian Society of Urology. Eur Urol 2000;37(4):413–20. [18] Roberts RO, Lieber MM, Rhodes T, Girman CJ, Bostwick DG, Jacobsen SJ. Prevalence of a physician-assigned diagnosis of prostatitis: the Olmsted County Study of Urinary Symptoms and Health Status Among Men. Urology 1998;51(4):578–84. [19] Schoenborn NL, Janssen EM, Boyd CM, Bridges JFP, Wolff AC, Pollack CE. Preferred clinician communication about stopping cancer screening among older US adults: results from a national survey. Jama Oncol 2018;4(8):1126–8. [20] Nordstrom T, Aly M, Clements MS, Weibull CE, Adolfsson J, Gronberg H. Prostate-specific antigen (PSA) testing is prevalent and increasing in Stockholm county, Sweden, despite no recommendations for PSA screening: results from a population-based study, 20032011. Eur Urol 2013;63(3):419–25. [21] Danckert B FJ, Engholm G, Hansen HL, et al. NORDCAN: Cancer incidence, mortality, prevalence and survival in the nordic countries, version 8.2 (26.03.2019). Association of the Nordic Cancer Registries. Danish Cancer Society. Available from: http://www.ancr.nu, accessed on 01/04/2019.

ARTICLE IN PRESS 8

B. Matti and K. Zargar-Shoshtari / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−8

[22] Ministry of Health. Cancer: historical summary 1948−2015. Wellington: Ministry of Health; 30 April 2018. [23] Young GJ, Harrison S, Turner EL, et al. Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study. Bmj Open 2017;7(10). [24] Ferlay J, Colombet M, Bray F. Cancer incidence in five continents, CI5plus: IARC CancerBase No. 9 [Internet]. Lyon, France: International Agency for Research on Cancer; 2018. Available from: http:// ci5.iarc.fr. [25] Zuzana O, Ross L, Fraser H, et al. Screening for prostate cancer in New Zealand general practice. J Med Screen 2013;20(1):49–51. [26] Jakupsstovu JOI, Brodersen J. Do men with lower urinary tract symptoms have an increased risk of advanced prostate cancer? Bmj-Brit Med J 2018;361. [27] National screening unit: NSU screening programmes. 2017; https:// www.nsu.govt.nz/. Accessed September 2018. [28] Godtman RA, Holmberg E, Lilja H, Stranne J, Hugosson J. Opportunistic testing versus organized prostate-specific antigen screening: outcome after 18 years in the Goteborg randomized population-based prostate cancer screening trial. Eur Urol 2015;68(3):354–60.

[29] Martin RM, Donovan JL, Turner EL, et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality the CAP randomized clinical trial. Jama-J Am Med Assoc 2018;319 (9):883–95. [30] Kilpelainen TP, Talala K, Raitanen J, et al. Prostate cancer and socioeconomic status in the finnish randomized study of screening for prostate cancer. Am J Epidemiol 2016;184(10):720–31. [31] Hugosson J, Godtman RA, Carlsson SV, et al. Eighteen-year follow-up of the goteborg randomized population-based prostate cancer screening trial: effect of sociodemographic variables on participation, prostate cancer incidence and mortality. Scand J Urol 2018;52(1):27–37. [32] Federman DG, Goyal S, Kamina A, Peduzzi P, Concato J. Informed consent for PSA screening: Does it happen? Eff Clin Pract 1999;2 (4):152–7. [33] Lamplugh M, Gilmore P, Quinlan T, Cornford P. PSA testing: Are patients aware of what lies ahead? Ann Roy Coll Surg 2006;88 (3):284–8. [34] Pan D, McCahy P. Patient knowledge about prostate-specific antigen (PSA) and prostate cancer in Australia. Bju International 2012;109: 52–6.