Epidemiology and organized testing for the diagnosis of prostate cancer in Sweden

Abstract

Prostate cancer is the most diagnosed cancer and the leading cause of cancer-related death among men in Sweden. The natural history and risk factors of prostate cancer, particularly within hereditary populations, have been extensively studied in the Swedish context. Despite the absence of national recommendations for prostate-specific antigen (PSA) screening, a large proportion of Swedish men undergo PSA testing. This unstructured testing approach has shown limited effectiveness and imposes a considerable burden on healthcare resources. To address these challenges, many regions in Sweden began implementing organized prostate cancer testing (OPT) in 2020. OPT targets specific age groups, providing them with comprehensive information about PSA testing, including its potential benefits and harms, to support informed individual decision-making. Subsequent PSA testing and follow-up procedures adhere to a standardized algorithm that incorporates individual risk factors, genetic predisposition, and the natural progression of prostate cancer. This review outlines the current recommendations, implementation strategies, and emerging frontiers for prostate cancer diagnosis in Sweden.

Graphical abstract

Keywords

epidemiology / organized prostate cancer testing / prostate cancer / screening

1 INTRODUCTION

The incidence of prostate cancer in Sweden doubled between 1995 and 2004, and currently, approximately one in five Swedish men receives a prostate cancer diagnosis during their lifetime. In 2022 alone, nearly 12 000 new cases were reported[1]. The sharp increase in incidence around the turn of the millennium was primarily attributed to the widespread adoption of prostate-specific antigen (PSA) blood testing and systematic biopsies for men with moderately elevated PSA levels.

The data presented in this review, including epidemiological and clinical outcomes, are derived primarily from the National Prostate Cancer Register (NPCR) of Sweden. Established in 1998, the NPCR captures data on 98% of all incident prostate cancer cases recorded in the legally mandated Swedish Cancer Registry[2]. In 2008, the NPCR underwent substantial expansion, including the introduction of computerized reporting, an increase in the number of registered clinical variables, and the incorporation of patient-reported outcome measures (PROMs)[3]. A large portion of NPCR data is now publicly accessible through interactive dashboards on the npcr.se platform. Furthermore, a national digital decision-support tool—the Individual Patient Overview (IPÖ) for prostate cancer—has been developed to facilitate personalized clinical decision-making[4].

Beyond its clinical utility, the NPCR also serves as a valuable research resource. In 2009, the Prostate Cancer data Base Sweden (PCBaSe) was established by linking NPCR data with other national health and demographic registries. PCBaSe includes data on more than 200 000 prostate cancer cases, five matched controls per case, and close relatives, offering a robust infrastructure for epidemiological and health services research[5,6].

Despite the lack of a national recommendation for PSA-based screening, PSA testing remains prevalent among Swedish men. However, this opportunistic testing has shown limited clinical benefit and has imposed a significant burden on healthcare resources. Between 1996 and 2016, it is estimated that more than 60 000 men in Sweden were overdiagnosed—receiving a prostate cancer diagnosis that would not have occurred without PSA testing and systematic biopsies[7,8]. Consequently, following the Swedish National Board of Health and Welfare's (Socialstyrelsen, SoS) 2018 decision to again advise against a national screening program, several Swedish regions initiated the development of organized prostate cancer testing (OPT).

OPT involves proactively inviting men in defined age groups and providing them with balanced information on the potential benefits and harms of PSA testing, thereby supporting informed individual decision-making. PSA testing and subsequent diagnostics are conducted according to standardized protocols that incorporate individual risk factors and the known natural history of prostate cancer[8]. This review aims to outline the current recommendations and implementation strategies for OPT in Sweden.

2 EPIDEMIOLOGY

2.1 Incidence (number of new cases)

Prostate cancer is the most commonly diagnosed cancer in Sweden, with more than 10 000 new cases reported annually. Between 2019 and 2020, the number of newly diagnosed cases declined from approximately 11 000 to 9000. This reduction was likely due to decreased diagnostic activity during the COVID-19 pandemic, as well as the implementation of updated national clinical guidelines in spring 2020, which recommended magnetic resonance imaging (MRI) prior to performing a prostate biopsy. In 2021, 10 199 new cases were registered, increasing to 12 004 in 2022, possibly reflecting a delayed, compensatory rise in diagnoses following the pandemic.

The incidence of prostate cancer rose sharply around the turn of the century, doubling between 1990 and 2004 (Figure 1). This increase was primarily driven by more intensive diagnostic efforts, including the introduction of PSA testing and systematic prostate biopsies. In addition, demographic changes—specifically, the growing number of elderly men in the population—contributed to the rising incidence. Currently, one in five Swedish men is diagnosed with prostate cancer during their lifetime. Age-standardized incidence trends are depicted in Figure 2.

Prostate cancer is strongly age-dependent. It is rare before the age of 50 and almost nonexistent before the age of 40. Increased diagnostic activity during the early 2000s contributed to a reduction in the median age at diagnosis, from 74 years in 1995 to 69 years in 2005. Detailed data on incidence, clinical characteristics at diagnosis, and primary treatment modalities are available through the NPCR, which also provides regional- and hospital-level statistics.

The sharp rise in incidence linked to increased diagnostic activity is largely attributable to the high prevalence of clinically insignificant prostate cancer. Histopathological examinations performed during autopsies and cysto-prostatectomies for bladder cancer have shown that prostate cancer is present in approximately one-third of men in their 60s and in half of men in their 80s[9,10]. There is a broad consensus that systematic prostate biopsies in men with PSA levels just above the intervention threshold frequently lead to diagnoses of indolent cancers that would not have produced symptoms during the patient's lifetime.

2.2 Mortality

Prostate cancer is the leading cause of cancer-related death among men in Sweden, accounting for approximately 5% of all male deaths. In 2021, prostate cancer was reported as the underlying cause of death for 2077 Swedish men. The majority of these deaths occur at an advanced age; half of the men who die from prostate cancer are over 82 years old, and three-quarters are older than 75.

The overall age-standardized mortality rate for prostate cancer showed a modest decline between 1970 and 2020, with a more consistent downward trend observed since the early 2000s (Figure 2). When stratified by age, a more pronounced reduction in mortality is evident across all age groups (Figure 3). Notably, the mortality rate among men younger than 75 years has decreased by approximately 50% over the past 15 years (Figure 4). Despite these improvements, the absolute number of prostate cancer deaths has remained relatively constant—at around 2400 annually over the past decade—due to the ongoing demographic shift toward an older male population.

2.3 Prevalence (number of men living with prostate cancer)

In 2021, approximately 125 000 men in Sweden were living with a prostate cancer diagnosis[9,10], representing a threefold increase compared to two decades earlier (Figure 5). This substantial rise in prevalence is attributable to several factors: the aging male population, a shift toward earlier-stage diagnoses, and improved survival among men with advanced disease, largely due to the introduction of more effective therapeutic options.

2.4 Future projections

The prevalence of prostate cancer in Sweden is expected to continue rising in the coming years[9]. However, projecting the magnitude of this increase—as well as future trends in incidence and mortality—remains challenging. Both prevalence and incidence are closely influenced by the extent of PSA testing and the diagnostic strategies employed for men with PSA levels above the intervention threshold. Moreover, prevalence is affected by the survival duration of men living with chronic prostate cancer.

Recent advances in systemic therapies have contributed to a growing number of men living with metastatic prostate cancer, significantly increasing the demand for healthcare resources within urologic oncology. This trend is anticipated to persist in the foreseeable future. According to projections by Statistics Sweden, the population of men aged 75 years and older is expected to rise from approximately 350 000 today to 580 000 by 2030. As a result, despite improvements in curative treatment strategies and prolonged survival, the absolute number of prostate cancer-related deaths is unlikely to decline in the coming decade.

3 NATURAL HISTORY

The natural history of a disease refers to its progression in the absence of medical intervention. For ethical and practical reasons, no contemporary studies can fully characterize the untreated natural course of prostate cancer. However, several earlier studies have monitored patients with various stages of prostate cancer who were observed without immediate treatment and later received hormonal therapy upon symptom onset[11–13].

Autopsy studies have demonstrated that microscopic prostate cancer can be present as early as in men's 20s, although clinically evident disease is extremely rare before the age of 50. The prevalence of microscopic (latent) prostate cancer increases steadily with age, exceeding 50% in men in their 80s. Tumors that remain asymptomatic throughout a man's life are referred to as clinically insignificant or latent prostate cancer. PSA screening frequently results in the diagnosis of such indolent cancers[14]. Unfortunately, in clinical practice, it is often challenging to determine whether a newly diagnosed tumor is clinically insignificant. On average, PSA testing advances the timing of a prostate cancer diagnosis by 5–15 years compared to detection without screening[14].

Non-metastatic prostate cancer is stratified into risk groups based on local tumor stage, Gleason score, and PSA level. For men who do not receive curative treatment, the risk of developing symptomatic disease and cancer-specific mortality depends on both the initial risk group and the patient's age at diagnosis[11]. Estimated prostate cancer-specific mortality rates at 10 years and 15 years after diagnosis for non-metastatic disease are as follows:

• Low-risk cancer: 4.5% at 10 years; 9% at 15 years.

• Intermediate-risk cancer: 13% at 10 years; 20% at 15 years.

• High-risk cancer: 29% at 10 years; 36% at 15 years[15].

Risk group definitions (Swedish National Care Program):

• Very low risk

º T1c, Gleason score 6, ≤ 8 mm total cancer in 1–4 of 8–12 systematic biopsy cores, PSA < 10 µg/L, and PSA density < 0.15 µg/L·cm³.

• Other low risk

º T1–T2a, Gleason score 6, and PSA < 10 µg/L not meeting the criteria for very low risk.

• Intermediate risk

º T2b–T2c and/or Gleason score 7 and/or PSA 10–19 µg/L.

• High risk

º One of the following:

▪ T3.

▪ Gleason score 8.

▪ Gleason score 4 + 3 = 7 in more than 50% of systematic biopsy cores.

▪ Gleason score 4 + 3 in targeted biopsies from PI-RADS 5 lesions.

▪ PSA 20–49 µg/L.

• Very high risk

º Two or more high-risk factors, or at least one of the following:

▪ T4.

▪ Gleason score 9–10.

▪ PSA ≥ 50 µg/L.

For patients with clinically detected lymph node–only metastases, median survival with hormonal therapy alone is approximately 6 years[16]. Historically, men diagnosed with distant metastases—usually involving the skeleton—had a median survival of around 3 years. However, recent advances in systemic therapies have significantly extended survival in many cases, with some patients now living more than 10 years post-diagnosis[17]. The presence of visceral metastases, particularly in the liver or lungs, is associated with shorter survival outcomes.

4 RISK FACTORS AND PREVENTION

4.1 Geographics, ethnic variations, and chronic inflammation

The prevalence of prostate cancer varies markedly across different regions and populations worldwide. The highest incidence is observed among men of African descent in the United States and the Caribbean, followed by White populations in the United States and Scandinavia. In contrast, the disease is relatively uncommon in Southeast Asia. This considerable geographic variation is believed to reflect a complex interplay between genetic susceptibility and environmental influences. Although the specific contributing factors remain incompletely understood, evidence suggests that adoption of a Western lifestyle—including dietary patterns and lower physical activity—may increase the risk of developing prostate cancer[18].

Chronic inflammation of the prostate is another suspected contributor to prostate carcinogenesis. Persistent infection may lead to long-term inflammation, promoting DNA damage through the sustained generation of reactive oxygen and nitrogen species by infiltrating leukocytes. Mutations in the tumor suppressor gene TP53 are frequently observed in prostate cancer cells that arise in chronically inflamed tissue[19].

4.2 Hereditary risk and genetics

Hereditary factors represent a significant risk for the development of prostate cancer. Men with a first-degree relative diagnosed with prostate cancer have a substantially increased risk of the disease. Sons of affected men have a 1.5–2-fold increased risk, while brothers have a 2–3-fold increased risk—corresponding to an absolute risk of approximately 15% by age 65 and up to 30% by age 75. The risk increases further if multiple family members are affected or if the diagnosis occurred at a younger age. Men with both a father and a brother diagnosed with prostate cancer—particularly if one was diagnosed before the age of 70–75—face an estimated 40–50% lifetime risk of developing the disease before that same age. Absolute risk estimates, compared to the general population, can be made even in the absence of a known germline mutation (see Table 1)[15,20,21].

Among men with three or more affected male relatives, the onset of prostate cancer tends to occur approximately 6 years earlier than in the general population, although the clinical progression and prognosis are typically similar. Notably, familial clustering of prostate cancer does not appear to confer a significantly increased risk of other cancers—except in families carrying a BRCA2 mutation, which is associated with elevated risks of breast and ovarian cancer.

A family history of prostate cancer on the maternal side alone generally does not significantly elevate a man's risk, unless the mother has been diagnosed with breast or ovarian cancer, which may indicate an underlying BRCA2 mutation. However, if a brother is also affected, the risk may approximate that associated with paternal inheritance[22].

The genetics behind hereditary susceptibility to prostate cancer is complex. Here we subdivide into:

4.2.1 High-penetrance genes

BRCA2: Mutations in the BRCA2 gene confer about 3-fold increased risk of prostate cancer. The disease often presents at a younger age, is poorly differentiated, and shows aggressive behavior[23].

HOXB13 (G84E mutation) mutation increases prostate cancer risk by approximately three times. About one-third of Swedish carriers are diagnosed before age 80. Although the median age at diagnosis is 3 years younger than average, the distribution of risk groups is similar. Sweden has the highest known prevalence: 1.3% in the general population and 4.5% among men with prostate cancer[24].

TP53 mutations (Li-Fraumeni syndrome) greatly increase the risk for several cancers, including early-onset, poorly differentiated prostate cancer[25].

4.2.2 Moderate-penetrance genes

BRCA1 mutations slightly increase prostate cancer risk but not enough to classify carriers as high-risk[26].

MSH2 (Lynch syndrome) significantly raise the lifetime risk of clinically significant prostate cancer (up to 23% per NCCN). Other Lynch syndrome-related genes (e.g., MLH1, MSH6) have only a modest effect on prostate cancer risk and do not warrant high-risk classification[27].

4.2.3 Common variants

In addition to rare, high-risk mutations, over 250 common genetic variants (single-nucleotide polymorphisms) associated with prostate cancer have been identified. Individually, these confer small risk increases but may collectively influence risk through polygenic risk scores.

4.3 Modifiable risk factors for prostate cancer prevention

The European Code Against Cancer outlines twelve evidence-based recommendations for reducing cancer risk. Among these, adopting a healthy lifestyle—such as maintaining a balanced diet, engaging in regular physical activity, and practicing safe sun exposure—constitutes a critical strategy for reducing the incidence of many cancers, including prostate cancer.

Several modifiable lifestyle factors have been associated with prostate cancer risk. Overweight and obesity, as well as high dairy consumption, have been identified as probable risk factors for prostate cancer, particularly for advanced stages of the disease[28–32]. The 2018 World Cancer Research Fund (WCRF) report provides strong evidence linking obesity with an increased risk of advanced prostate cancer (WCRF, 2018). Conversely, some dietary components—such as soy products, tomatoes (rich in lycopene), pomegranate juice, and green tea—have been associated with a potentially reduced risk of prostate cancer in epidemiological studies. However, the evidence remains inconclusive and, in many cases, contradictory[30].

Micronutrients such as selenium and vitamin E have also been investigated for their protective potential. Nevertheless, findings from a large randomized trial (SELECT) demonstrated no benefit; rather, an increased risk of prostate cancer was observed among men who received these supplements[33]. Furthermore, the 2018 WCRF report concluded there is strong evidence that beta-carotene, whether consumed through food or supplements, does not influence prostate cancer risk.

Tobacco smoking, though not a direct etiological factor for prostate cancer, is associated with numerous adverse health outcomes and has been linked to more aggressive disease. Smoking may increase the risk of developing high-grade prostate cancer, recurrence following curative treatment, and prostate cancer-specific mortality[34–37]. Additionally, among men with conservatively managed low- or intermediate-risk prostate cancer, the risk of dying from smoking-related conditions exceeds the risk of death from the cancer itself[38]. Smoking cessation, therefore, remains a key component of overall cancer risk reduction and long-term health preservation.

4.4 Primary prevention

4.4.1 Alpha reductase inhibitors

Two drugs—finasteride and dutasteride—are approved 5-alpha reductase inhibitors. A major randomized study showed that 7 years of finasteride reduced the incidence of low-grade prostate cancer (Gleason ≤ 6) by 6 percentage points but slightly increased the diagnosis of higher-grade cancers (Gleason 7–10) by 1.3 percentage points[39]. However, overall prostate cancer mortality was unchanged[40]. This increase in high-grade diagnoses may be due to improved detection rather than a true increase in aggressive cancers[29]. Registry studies suggest these inhibitors reduce the risk of being diagnosed with Gleason 6–7 cancers but do not affect the incidence of Gleason 8–10 cancers[41–43]. Dutasteride, over 4 years, similarly reduced the detection of low-grade cancer in men with PSA 2.5–10 µg/L, but had no effect on Gleason ≥ 7 cancers[44]. A Swedish registry study found no increased risk of prostate cancer death with 5-alpha reductase inhibitors after 8 years of follow-up[45].

4.4.2 Aspirin, statins, and metformin

Meta-analyses show that long-term use of aspirin and other NSAIDs is associated with a reduced risk of death from various cancers, including prostate cancer[46,47], and possibly a lower risk of advanced prostate cancer[48]. Statins have also been linked to reduced risks of advanced disease and mortality[49,50]. Similarly, metformin use may be associated with a lower risk of prostate cancer[51]. Despite these associations, current evidence is insufficient to recommend any of these medications solely for prostate cancer prevention.

4.4.3 Captopril and ACE inhibitors

Based on a previous epidemiological study indicating that captopril users exhibited a reduced risk of subsequent prostate cancer[52], our research group conducted a small, randomized study in 2009 involving 62 patients following radical prostatectomy (RP)[53]. This study demonstrated a reduction in biochemical failure after RP in patients who received postoperative captopril treatment (Figure 6). Captopril (d-3-mercapto-2-methylpropanoyl-l-proline) is an inhibitor of angiotensin I-converting enzyme (ACE, CD 143), a type I cell surface zinc metallopeptidase. Additionally, captopril may inhibit matrix metalloproteases through direct interaction with the zinc atom on prostasomes. This inhibition could act synergistically with ACE inhibition, thereby suppressing the development and progression of prostate cancer. There is also evidence suggesting that ACE plays a role in the pathophysiology of carcinomas at a local level. ACE is differentially expressed in various malignancies and influences tumor cell proliferation, migration, angiogenesis, and metastatic potential[54]. However, to date, no large-scale, randomized, double-blind, placebo-controlled study has been conducted to confirm the preventive effects of ACE inhibitors against prostate cancer.

5 PROSTATE CANCER SCREENING

5.1 Current landscape

Prostate cancer screening has long been a subject of debate. Initial studies employed digital rectal examination (DRE), but the introduction of PSA testing in the early 1990s markedly increased interest in early detection. As early as 1994, PSA testing was shown to identify significantly more cases of organ-confined prostate cancer compared to DRE[55]. Following these findings, widespread PSA testing of asymptomatic men expanded rapidly in the United States and, with some delay, in Europe.

This surge in interest led to the initiation of multiple randomized controlled trials across Europe, in which participants were assigned either to repeated PSA testing or to a control group. These trials were primarily designed to evaluate prostate cancer-specific mortality under an intention-to-screen framework—wherein all prostate cancer deaths were counted regardless of actual screening participation. This effort culminated in the establishment of the European Randomized Study of Screening for Prostate Cancer (ERSPC) in the early 1990s, involving eight centers. The first mortality outcomes were published in 2009, with the most recent update released in 2019[56].

Notably, the Swedish Göteborg 1 trial, initiated independently in 1995 and later integrated into ERSPC, has reported up to 22 years of follow-up data[57]. Both ERSPC and Göteborg 1 demonstrated a 20%–30% relative reduction in prostate cancer-specific mortality associated with PSA-based screening.

In contrast, the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial—initiated in the late 1990s—reported no significant difference in mortality. However, substantial contamination of the control group, with widespread off-study PSA testing, compromised the trial's interpretability regarding screening efficacy[58].

Similarly, a large UK study evaluating one-time PSA testing failed to show a mortality benefit[59]. These findings suggest that single, opportunistic PSA testing is ineffective and that structured, interval-based screening protocols are essential to detect clinically significant tumors in a timely manner.

Current evidence suggests that lethal prostate tumors tend to progress rapidly and require frequent PSA screening (every 2–3 years) for early detection. However, individualized screening intervals based on baseline PSA levels are now recommended. For men with PSA < 1.0 µg/L, screening intervals of 6–8 years may be appropriate[60]. Conversely, PSA screening is not advised for men with a life expectancy of less than 10 years, as the mortality benefit is delayed.

A major limitation of PSA-based screening is its low specificity and the high prevalence of indolent cancers, leading to substantial overdiagnosis and overtreatment[61]. This concern has catalyzed research into improved risk stratification, notably through the incorporation of MRI.

In the Stockholm3 study, 49 118 men aged 50–74 were invited, and 12 750 participated. Among the 1532 men with elevated PSA, participants were randomized to receive either MRI with targeted biopsy or systematic biopsy. Over half of those in the MRI group avoided biopsy due to absence of suspicious lesions. Detection of clinically insignificant cancer was significantly lower in the MRI group (4% vs. 12%), while detection of clinically significant cancers remained comparable[62].

The Göteborg 2 study, involving 33 875 men aged 50–60, evaluated three MRI-based screening protocols. All arms employed MRI for elevated PSA, but differed in biopsy strategy. Arm 1 used both systematic and targeted biopsies; Arms 2 and 3 used targeted biopsy alone. MRI-targeted biopsy alone halved the risk of overdiagnosis and significantly reduced the biopsy rate (2.8% vs. 6.8%) compared to combined biopsy. Although detection of significant cancer was slightly lower with targeted biopsy alone, this difference was not statistically significant[63]. Ongoing MRI-based screening trials in Finland and Germany aim to further refine risk-adapted protocols.

5.2 National recommendations in Sweden

The Swedish National Board of Health and Welfare has conducted two formal assessments (2014 and 2018) regarding the implementation of a national prostate cancer screening program. On both occasions, the Board concluded that the benefits of systematic screening do not clearly outweigh the potential harms at the population level.

Nonetheless, the Board recommends that men who express an interest in PSA testing should be provided with balanced, evidence-based information regarding its potential risks and benefits. Informed individuals may then undergo testing if they choose. This approach is consistent with recommendations from most international health authorities, with the notable exception of Lithuania, where opportunistic PSA testing is actively recommended during primary care visits.

6 OPT

6.1 Background and rationale

Although there is currently no national recommendation for PSA testing in asymptomatic men, opportunistic testing remains widespread in Sweden. This unstructured approach is suboptimal—both in terms of effectiveness and resource utilization—when compared to systematic, organized strategies. In light of this, following the Swedish National Board of Health and Welfare's renewed decision in 2018 not to implement a national screening program, several regions initiated OPT programs.

OPT entails systematically offering men in defined age groups objective information about the benefits and risks of PSA testing, thereby enabling informed decision-making. Those who OPT to participate undergo PSA testing and, if necessary, further diagnostic evaluation according to a standardized algorithm (Figure 7). This structured model was developed to address the inefficiencies associated with previous opportunistic testing practices and to promote consistency and equity in prostate cancer diagnostics.

Since 2020, most of Swedish regions have launched OPT initiatives. As of spring 2024, 15 out of 21 regions had implemented such programs. Approximately 150 000 men have been offered participation, with a 48% acceptance rate. These initiatives are supported by the National Board of Health and Welfare, which views them as a means to improve diagnostic efficiency, reduce inequity, and contribute valuable data to address key knowledge gaps regarding PSA-based screening[64].

Importantly, organized testing differs fundamentally from formal population-wide screening. The Swedish National Board of Health and Welfare clarifies this distinction:

Organized PSA testing means that men receive clear information about the advantages and disadvantages of PSA testing and then make an individual decision on whether to get tested or not. Organized PSA testing should therefore not be confused with a national screening program, where testing is recommended, and men receive a direct invitation to undergo testing. Conducting organized PSA testing within the framework of research and development is fully in line with the recommendations outlined in the national guidelines for prostate cancer.

This approach allows for structured implementation and scientific evaluation while respecting the current recommendations against nationwide screening.

In December 2022, the European Union issued a recommendation for member states to progressively implement and assess organized prostate cancer screening programs. This position reflects concerns over ineffective opportunistic testing, recognizes recent advancements in imaging and targeted biopsy techniques, and underscores the need for structured testing pathways. The EU's recommendation is aligned with the Swedish model, and Sweden's experience is now serving as a reference for other European countries seeking to improve the efficiency and quality of prostate cancer diagnostics.

6.2 Implementation of OPT

6.2.1 Eligibility criteria

OPT in Sweden typically targets men aged 50 years to 74 years. The core objective is to ensure that all individuals within this age group are provided with balanced, evidence-based information about the potential advantages and limitations of PSA testing, thereby supporting informed decision-making.

The implementation of OPT has varied regionally. For example, Region Skåne initiated its program in 2020 and has progressively expanded its inclusion criteria to additional age groups. Other regions have adopted similar staggered approaches, allowing for local adaptation based on healthcare capacity and population demographics.

6.2.2 Testing workflow and follow-up protocol

Eligible men are invited via mail to participate in the OPT program. The invitation includes detailed written information on PSA testing, allowing individuals to make an informed choice. If a recipient does not respond, a follow-up invitation is sent after 2 years.

Men who accept the invitation undergo a PSA blood test. If PSA levels are within normal limits, the timing of the next test is based on age and PSA concentration:

• PSA < 1.0 µg/L (age ≤ 65 years): Retesting every 6 years.

• PSA < 1.0 µg/L (age > 65 years): No further testing recommended.

• PSA 1.0–2.9 µg/L (ages < 70); PSA 1.0–4.9 µg/L (ages 70–74): Retesting every 2 years until age 74.

• PSA increase >1.0 µg/L from prior test: Repeat test after 1 year.

If PSA is elevated, the individual is referred for multiparametric magnetic resonance imaging (mpMRI) of the prostate.

MRI findings guide further action using PI-RADS (prostate imaging reporting and data system) scoring in conjunction with PSA density (PSAD):

• PI-RADS 1–2 with PSAD < 0.15, or PI-RADS 3 with PSAD < 0.10: No immediate action; next MRI and PSA reassessment after approximately 2 years.

• PI-RADS 1–2 with PSAD ≥ 0.15, PI-RADS 3 with PSAD ≥ 0.10, or PI-RADS 4–5: Referral to urology for prostate biopsy, typically using MRI–ultrasound fusion-guided technique.

If the biopsy does not detect cancer, the patient is either scheduled for re-biopsy or monitored with follow-up MRI and PSA testing in approximately 2 years.

This structured algorithm aims to balance early cancer detection with minimization of overdiagnosis, leveraging MRI and PSAD as triage tools to refine the diagnostic pathway (Figure 7).

6.3 Individual-based PSA testing

For asymptomatic men who express interest in prostate cancer screening outside of organized programs, individual-based PSA testing remains an option. In such cases, men should be provided with written, evidence-based information that outlines the potential benefits and limitations of PSA testing. Informed consent is essential to support shared decision-making.

Men who elect to proceed with PSA testing following this information should undergo a DRE prior to referral under the Swedish Standardized Cancer Care Pathway (SVF). This step is crucial to ensure appropriate prioritization by the receiving clinical unit.

6.3.1 Eligibility and life expectancy considerations

PSA testing should be discouraged in asymptomatic men with a life expectancy of less than 10–15 years, as the potential benefits are unlikely to materialize within that time frame. For reference, average remaining life expectancy among Swedish men is:

• 15 years at age 70.

• 12 years at age 75.

• years at age 80.

These averages are derived from population data provided by Statistics Sweden and include both healthy and comorbid individuals. Clinicians should tailor life expectancy assessments based on individual health status, comorbidities, and risk factors such as smoking or genetic predisposition.

Conversely, men with an expected survival > 10–15 years, who wish to proceed after reviewing the relevant information, may undergo regular PSA testing, with or without DRE. Referral to urology under the SVF should occur under the following circumstances:

• Men < 70 years: PSA ≥ 3.0 µg/L.

• Men aged 70–80 years: PSA ≥ 5.0 µg/L.

• Men > 80 years: PSA ≥ 7.0 µg/L.

• Men on 5-alpha reductase inhibitors: Refer if PSA exceeds half of the applicable threshold.

Additionally, any palpable hardening of the prostate on DRE warrants referral, regardless of PSA level.

6.3.2 Special considerations

• Men under 50 years of age without symptoms or a family history of prostate cancer are unlikely to benefit from PSA testing and should generally not be tested.

• Men with hypogonadism (testosterone < 8 mmol/L) and a functioning prostate should undergo PSA testing at 2-year intervals. In contrast, men without documented hypogonadism can be assumed to have normal testosterone levels and do not require altered testing frequency.

6.3.3 Overuse in low-risk populations

Several longitudinal studies[45–51] have demonstrated that men with very low PSA values have a negligible risk of developing clinically significant prostate cancer in subsequent decades. Nonetheless, many such individuals are tested annually, which constitutes unnecessary overtesting without added clinical benefit. Testing intervals should therefore be adjusted based on baseline PSA to avoid overtreatment and preserve healthcare resources.

6.4 Management of men in the hereditary risk

6.4.1 PSA testing

PSA testing should begin at age 40 and continue until curative treatment for prostate cancer is no longer a viable option:

• Men with a father or brother diagnosed with prostate cancer and at least one first-degree relative of these individuals also diagnosed with prostate cancer. One of the family members should have been diagnosed before the age of 75.

• Men with a known disease-associated variant (class 4 or class 5 according to the ACMG criteria) in any of the genes BRCA2, MSH2, or TP53.

6.4.2 Follow-up of men in the hereditary risk group

Men in the hereditary risk group should be recommended follow-up starting at the age of 40. The follow-up should occur in primary care as long as the PSA level is < 2 µg/L and should be discontinued when curative treatment for prostate cancer would no longer be considered, that is, when the expected remaining lifetime is shorter than 10–15 years. The first check should include a PSA test and DRE. Afterward, follow-up should proceed as follows:

• PSA < 1 µg/L: PSA test every 2 years in primary care.

• PSA 1–1.9 µg/L: PSA test annually in primary care.

• PSA ≥ 2 µg/L: Management in urological clinic. The man should be offered an MRI of the prostate and a DRE. Targeted and/or systematic biopsies should be offered generously, especially for men with a BRCA2 mutation. If no cancer is detected, the man should be followed up in a urological unit with a maximum interval of 1 year.

6.4.3 Cancer genetic

Investigation and genetic testing recommendations for men with prostate cancer who should be offered cancer genetic investigation:

• Men younger than 60 years old who have metastatic prostate cancer and/or a Gleason score of 5, and at least one first-degree relative diagnosed with breast cancer, ovarian cancer, prostate cancer, or pancreatic cancer, should be offered testing for a BRCA2 mutation.

• For men younger than 50 years old who have metastatic prostate cancer with a Gleason score of 5, consider testing for TP53. For men with multiple family members with breast or ovarian cancer, refer to the National Care Program for Breast Cancer, Chapter 10, for details.

• If the family history suggests another hereditary cancer syndrome, men should be offered testing for other relevant genes.

6.4.4 Testing for BRCA2

If a mutation in the BRCA2 gene is detected, it can be significant not only for the individual but also for close relatives, both male and female, as they may also carry the mutation. Women with such a mutation have a significantly increased risk of breast cancer and ovarian cancer (see the National Care Program for Breast Cancer, Chapter 10), while men with the mutation have a substantial risk of:

• Developing prostate cancer as early as their 50s.

• Having cancer with low PSA production.

• Developing low-risk cancer that progresses to incurable cancer under active monitoring.

• Developing metastatic prostate cancer.

• Developing castration-resistant prostate cancer with particularly poor prognosis.

BRCA2 (and BRCA1) mutations are also significant for the treatment of metastatic prostate cancer, as PARP inhibitors are effective specifically for cancers with such mutations. Therefore, the care program group recommends that men with early-onset, severe prostate cancer who have BRCA2-associated cancer in their family should be offered oncogenetic testing (see the recommendation box above). The defined group is estimated to include approximately a hundred men per year.

6.4.5 Other genes and biomarkers

Routine germline testing for genes beyond BRCA2 is not currently recommended. The European Association of Urology (EAU), together with EANM, ESTRO, ESUR, ISUP, and SIOG, has issued guidance supporting a broader constitutional mutation panel for blood-based analysis, including BRCA1, BRCA2, ATM, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

However, outside of cases involving BRCA2 mutations or families with clear hereditary cancer syndromes, current evidence does not support widespread implementation of multigene panel testing. Data remain limited regarding the clinical utility of such testing for both index patients and their relatives. As a result, the Swedish care program group recommends that multigene testing should be limited to those fulfilling specific clinical or familial criteria, as outlined in current national recommendations.

For example, ATM (ataxia-telangiectasia mutated) gene mutations are associated with up to a 4-fold increased risk of prostate cancer and are more frequently observed in men with younger age at diagnosis, high Gleason scores, or metastatic disease. However, even among these higher-risk groups, ATM mutations are relatively uncommon (1%–2%), limiting the utility of routine testing. Moreover, screening asymptomatic men for heterozygous carrier status is not advised, given the lack of proven benefit in clinical decision-making.

7 THE FUTURE OF PROSTATE CANCER HEALTHCARE

Prostate cancer remains the most common malignancy among Swedish men. Each year, more than 20 000 men are investigated for suspected prostate cancer, and over 100 000 undergo follow-up for elevated PSA levels. Advances in diagnostics, imaging, and treatment strategies have made the management of prostate cancer increasingly complex, necessitating a high level of specialized clinical expertise.

Treatment modalities—such as robot-assisted surgery, precision radiotherapy, and systemic therapies (e.g., hormonal treatments, chemotherapy, targeted agents)—require individualized decision-making and coordination across disciplines. In parallel, the number of men living with prostate cancer continues to rise, now exceeding 130 000. While many are disease-free and monitored only with annual PSA testing, others contend with treatment-related side effects or progressive disease.

To address these growing demands, Sweden is exploring the development of specialized prostate cancer centers, designed to deliver integrated, high-quality care for patients with suspected or confirmed prostate cancer. A small number of such centers have already been established, with the expectation that more will follow. These centers aim to streamline care pathways and improve outcomes through centralized diagnostics, shared decision-making, and optimized resource allocation.

Emerging frontiers: Biomarkers and artificial intelligence (AI)

Technological innovation is accelerating change in prostate cancer care. Recent developments in AI have shown promise in improving diagnostic accuracy, risk stratification, and workflow efficiency. Furthermore, biomarker research is advancing rapidly.

A notable study from Karolinska Institutet, Stockholm, recently identified promising urine-based biomarkers using mRNA, immunohistochemistry, and proteomics in a cohort of over 2000 patients with and without prostate cancer. Using machine learning models, researchers achieved an area under the curve of 0.92 for detecting prostate cancer. These biomarkers were also significantly associated with tumor grade, suggesting potential not only for detection but also for risk classification[65].

These findings pave the way for a non-invasive diagnostic test that could one day inform not only the presence of prostate cancer, but also the biological aggressiveness of the tumor and individualized treatment strategies. Such a development could radically transform screening, diagnosis, and treatment decision-making. Envision a future where a single urine test can reveal whether a man has prostate cancer, what subtype it is, and what treatment (if it needed) is most appropriate. Realizing this vision will depend on continued research, cross-disciplinary collaboration, and sustained investment in precision medicine and data science. The evolution of prostate cancer care is well underway.

8 CONCLUSION

Prostate cancer remains the most commonly diagnosed malignancy and the leading cause of cancer-related mortality among men in Sweden. Extensive research conducted within the country has contributed to a deeper understanding of the disease's natural history and associated risk factors.

Despite the absence of national recommendations for population-wide PSA screening, opportunistic PSA testing is widespread. However, such unstructured testing is inefficient, clinically suboptimal, and imposes a substantial burden on healthcare resources. In response, Sweden has introduced OPT in several regions. This approach involves actively informing men in specific age groups about the potential benefits and risks of PSA testing, allowing for informed decision-making and individualized participation. OPT follows a structured diagnostic algorithm that incorporates PSA levels, genetic predisposition, and knowledge of disease progression to optimize detection and minimize overdiagnosis. This risk-adapted strategy represents a more equitable and evidence-based framework for early detection.

Looking ahead, emerging technologies—including non-invasive urine-based biomarker assays and AI-driven decision tools—offer the promise of revolutionizing prostate cancer diagnostics. These innovations may soon allow clinicians to diagnose, classify, and guide treatment decisions for prostate cancer using a single, highly accurate urine test. Sweden's ongoing efforts in structured testing, biomarker discovery, and precision oncology place it at the forefront of prostate cancer care innovation.

References

[1] Swedish National Board of Health and Welfare (Socialstyrelsen). Statistikdatabas för cancer.

[2] Tomic K, Sandin F, Wigertz A, Robinson D, Lambe M, Stattin P. Evaluation of data quality in the National Prostate Cancer Register of Sweden. Eur J Cancer. 2015;51(1):101–111.

[3] Stattin P, Sandin F, Loeb S, Robinson D, Lissbrant IF, Lambe M. Public online reporting from a nationwide population-based clinical prostate cancer register. BJU Int. 2018;122:8–10.

[4] Van Hemelrijck M, Wigertz A, Sandin F, Garmo H, Hellstrom K, Fransson P, et al. Cohort profile: the national prostate cancer register of Sweden and prostate cancer data base Sweden 2.0. Int J Epidemiol. 2013;42:956–967.

[5] Tomic K, Westerberg M, Robinson D, Garmo H, Stattin P. Proportion and characteristics of men with unknown risk category in the national prostate cancer register of Sweden. Acta Oncol. 2016;55:1461–1466.

[6] Beckmann K, Garmo H, Franck Lissbrant I, Stattin P. The value of real-world data in understanding prostate cancer risk and improving clinical care: examples from Swedish registries. Cancers. 2021;13(4):875.

[7] Bergengren O, Westerberg M, Holmberg L, Stattin P, Bill-Axelson A, Garmo H. Variation in prostate-specific antigen testing rates and prostate cancer treatments and outcomes in a national 20-year cohort. JAMA Netw Open. 2021;4(5):e219444.

[8] The Confederation of Regional Cancer Centres (Reghionala cancercentrum I samverkan): Organised prostate cancer testing. 2025.

[9] Bell KJL, Del Mar C, Wright G, Dickinson J, Glasziou P. Prevalence of incidental prostate cancer: A systematic review of autopsy studies. Int J Cancer. 2015;137(7):1749–1757.

[10] Trpkov K, Yilmaz A, Bismar TA, Montironi R. Insignificant’ prostate cancer on prostatectomy and cystoprostatectomy: variation on a theme ‘low-volume/low-grade’ prostate cancer? BJU Int. 2010;106(3):304–315.

[11] Rider JR, Sandin F, Andrén O, Wiklund P, Hugosson J, Stattin P. Long-term outcomes among noncuratively treated men according to prostate cancer risk category in a nationwide, population-based study. Eur Urol. 2013;63(1):88–96.

[12] Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014;370(10):932–942.

[13] Stattin P, Holmberg E, Johansson JE, Holmberg L, Adolfsson J, Hugosson J, et al. Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study. J Natl Cancer Inst. 2010;102(13):950–958.

[14] Draisma G, Boer R, Otto SJ, van der Cruijsen IW, Damhuis RAM, Schroder FH, et al. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst. 2003;95(12):868–878.

[15] Hemminki K, Czene K. Age specific and attributable risks of familial prostate carcinoma from the family-cancer database. Cancer. 2002 Sep 15;95(6):1346–1353.

[16] Aus G, Robinson D, Rosell J, Sandblom G, Varenhorst E, South-East Region Prostate Cancer G. Survival in prostate carcinoma--outcomes from a prospective, population-based cohort of 8887 men with up to 15 years of follow-up: results from three countries in the population-based National Prostate Cancer Registry of Sweden. Cancer. 2005;103(5):943–951.

[17] Westerberg M, Franck Lissbrant I, Damber JE, Robinson D, Garmo H, Stattin P. Temporal changes in survival in men with de novo metastatic prostate cancer: nationwide population-based study. Acta Oncol. 2020;59(1):106–111.

[18] Dasgupta P, Baade PD, Aitken JF, Ralph N, Chambers SK, Dunn J. Geographical variations in prostate cancer outcomes: a systematic review of international evidence. Front Oncol. 2019;9:238.

[19] Stark T, Livas L, Kyprianou N. Inflammation in prostate cancer progression and therapeutic targeting. Transl Androl Urol. 2015;4(4):455–463.

[20] Bratt O, Drevin L, Akre O, Garmo H, Stattin P. Family history and probability of prostate cancer, differentiated by risk category: a nationwide population-based study. J Natl Cancer Inst. 2016;108(10):djw110.

[21] Grönberg H, Damber L, Damber JE. Familial prostate cancer in Sweden. A nationwide register cohort study. Cancer. 1996;77(1):138–143.

[22] Bratt O, Garmo H, Adolfsson J, Bill-Axelson A, Holmberg L, Lambe M, et al. Effects of prostate-specific antigen testing on familial prostate cancer risk estimates. J Natl Cancer Inst. 2010;102(17):1336–1343.

[23] Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373:1697–1708.

[24] Karlsson R, Aly M, Clements M, Zheng L, Adolfsson J, Xu J, et al. A population-based assessment of germline HOXB13 G84E mutation and prostate cancer risk. Eur Urol. 2014;65(1):169–176.

[25] Schitcu VH, Raduly L, Zanoaga O, Jurj A, Munteanu VC, Budisan L, et al. TP53 gene implications in prostate cancer evolution: potential role in tumor classification. Med Pharm Rep. 2023;96(4):384–391.

[26] Bancroft EK, Page EC, Castro E, Lilja H, Vickers A, Sjoberg D, et al. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur Urol. 2014;66:489–499.

[27] Guedes LB, Antonarakis ES, Schweizer MT, Mirkheshti N, Almutairi F, Park JC, et al. MSH2 loss in primary prostate cancer. Clin Cancer Res. 2017;23(22):6863–6874.

[28] Häggström C, Stocks T, Ulmert D, Bjørge T, Ulmer H, Hallmans G, et al. Prospective study on metabolic factors and risk of prostate cancer. Cancer. 2012;118(24):6199–6206.

[29] Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013;63(5):800–809.

[30] Mandair D, Rossi RE, Pericleous M, Whyand T, Caplin ME. Prostate cancer and the influence of dietary factors and supplements: a systematic review. Nutr Metab. 2014;11:30.

[31] Harrison S, Tilling K, Turner EL, Martin RM, Lennon R, Lane JA, et al. Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen. Cancer Causes Control. 2020;31(5):431–449.

[32] World Cancer Research Fund. Diet, nutrition and physical activity and prostate cancer: World Cancer Research Fund International. 2018 [cited 2023 Sep 08].

[33] Klein EA, Thompson Jr. IM, Tangen CM, Crowley JJ, Lucia MS, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549–1556.

[34] Ho T, Howard LE, Vidal AC, Gerber L, Moreira D, McKeever M, et al. Smoking and risk of low- and high-grade prostate cancer: results from the REDUCE study. Clin Cancer Res. 2014;20(20):5331–5338.

[35] Moreira DM, Aronson WJ, Terris MK, Kane CJ, Amling CL, Cooperberg MR, et al. Cigarette smoking is associated with an increased risk of biochemical disease recurrence, metastasis, castration-resistant prostate cancer, and mortality after radical prostatectomy: results from the SEARCH database. Cancer. 2014;120(2):197–204.

[36] Kenfield SA. Smoking and prostate cancer survival and recurrence. JAMA. 2011;305(24):2548–2555.

[37] Islami F, Moreira DM, Boffetta P, Freedland SJ. A systematic review and meta-analysis of tobacco use and prostate cancer mortality and incidence in prospective cohort studies. Eur Urol. 2014;66(6):1054–1064.

[38] Rider JR, Sandin F, Andrén O, Wiklund P, Hugosson J, Stattin P. Long-term outcomes among noncuratively treated men according to prostate cancer risk category in a nationwide, population-based study. Eur Urol. 2013;63(1):88–96.

[39] Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215–224.

[40] Thompson Jr. IM, Goodman PJ, Tangen CM, Parnes HL, Minasian LM, et al. Long-term survival of participants in the prostate cancer prevention trial. N Engl J Med. 2013;369(7):603–610.

[41] Robinson D, Garmo H, Bill-Axelson A, Mucci L, Holmberg L, Stattin P. Use of 5 -reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study. BMJ. 2013;346:f3406.

[42] Preston MA, Wilson KM, Markt SC, Ge R, Morash C, Stampfer MJ, et al. 5α-Reductase Inhibitors and Risk of High-Grade or Lethal Prostate Cancer. JAMA Intern Med. 2014;174(8):1301–1307.

[43] Wallerstedt A, Strom P, Gronberg H, Nordstrom T, Eklund M. Risk of Prostate Cancer in Men Treated With 5α-Reductase Inhibitors-A Large Population-Based Prospective Study. JNCI J Natl Cancer Inst. 2018;110(11):1216–1221.

[44] Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192–1202.

[45] Björnebo L, Nordström T, Discacciati A, Palsdottir T, Aly M, Grönberg H, et al. Association of 5α-reductase inhibitors with prostate cancer mortality. JAMA Oncol. 2022;8(7):1019.

[46] Rothwell PM, Fowkes FGR, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41.

[47] Cuzick J, Thorat MA, Bosetti C, Brown PH, Burn J, Cook NR, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol. 2015;26(1):47–57.

[48] Mahmud SM, Franco EL, Aprikian AG. Use of nonsteroidal anti-inflammatory drugs and prostate cancer risk: a meta-analysis. Int J Cancer. 2010;127(7):1680–1691.

[49] Bansal D, Undela K, D'Cruz S, Schifano F. Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLoS One. 2012;7(10):e46691.

[50] Yu O, Eberg M, Benayoun S, Aprikian A, Batist G, Suissa S, et al. Use of statins and the risk of death in patients with prostate cancer. J Clin Oncol. 2014;32(1):5–11.

[51] Yu H, Yin L, Jiang X, Sun X, Wu J, Tian H, et al. Effect of metformin on cancer risk and treatment outcome of prostate cancer: a meta-analysis of epidemiological observational studies. PLoS One. 2014;9(12):e116327.

[52] Ronquist G, Rodríguez LAG, Ruigómez A, Johansson S, Wallander MA, Frithz G, et al. Association between captopril, other antihypertensive drugs and risk of prostate cancer. Prostate. 2004;58:50–56.

[53] Ronquist G, Frithz G, Wang YH, Lindeborg T. Captopril may reduce biochemical (prostate-specific antigen) failure following radical prostatectomy for clinically localized prostate cancer. Scand J Urol Nephrol. 2009;43:32–36.

[54] Bauvois B. Transmembrane proteases in cell growth and invasion: new contributors to angiogenesis? Oncogene. 2004;23:317–329.

[55] Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol. 1994;151(5):1283–1290.

[56] Hugosson J, Roobol MJ, Månsson M, Tammela TLJ, Zappa M, Nelen V, et al. A 16-yr follow-up of the European randomized study of screening for prostate cancer. Eur Urol. 2019;76(1):43–51.

[57] Frånlund M, Månsson M, Godtman RA, Aus G, Holmberg E, Kollberg KS, et al. Results from 22 years of follow up in the Göteborg randomized population-based prostate cancer screening trial. J Urol. 2022;208(2):292–300.

[58] Andriole GL, Crawford ED, Grubb 3rd RL, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310–1319.

[59] Martin RM, Donovan JL, Turner EL, Metcalfe C, Young GJ, Walsh EI, et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: The CAP randomized clinical trial. JAMA. 2018;319(9):883–895.

[60] Vickers AJ, Ulmert D, Sjoberg DD, Bennette CJ, Bjork T, Gerdtsson A, et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study. BMJ. 2013;346:f2023.

[61] Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010;11(8):725–732.

[62] Hugosson J, Månsson M, Wallström J, Axcrona U, Carlsson SV, Egevad L, et al. Prostate cancer screening with PSA and MRI followed by targeted biopsy only. N Engl J Med. 2022;387(23):2126–2137.

[63] Eklund M, Jäderling F, Discacciati A, Bergman M, Annerstedt M, Aly M, et al. MRI-Targeted or standard biopsy in prostate cancer screening. N Engl J Med. 2021;385(10):908–920.

[64] Alterbeck M, Järbur E, Thimansson E, Wallström J, Bengtsson J, Björk-Eriksson T, et al. Designing and implementing a population-based organised prostate cancer testing programme. Eur Urol Focus. 2022;8(6):1568–1574.

[65] Smelik M, Gonzalez D-RD, An X, Heer R, Henningsohn L, Li X, et al. Combining spatial transcriptomics, pseudotime, and machine learning enables discovery of biomarkers for prostate cancer. Cancer Res. 2025;85(13):2514–2526.

RIGHTS & PERMISSIONS

2025 The Author(s). UroPrecision published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.