Prostate Cancer Testing in the Modern Era: Does the Digital Rectal Exam Still Play a Role?

Table of Contents

• Key Points
• Why Prostate Cancer Is a Growing Concern
• PSA Blood Testing: Widely Used but Imperfect
• The Prostate Health Index (PHI): Solving the Gray Zone Problem
• MRI: High-Resolution Imaging Changes the Game
• PSMA-PET: A Powerful Tool with Practical Limits
• Artificial Intelligence and Genetic Testing
• Other Blood and Urine Biomarkers
• Digital Rectal Examination: The Traditional Exam Under Scrutiny
• Balancing Strengths and Weaknesses: A Multimodal Approach
• Conclusions: What Should Patients Take Away?
• Frequently Asked Questions
• Source Information

Key Points

• PSA testing is widely used but not cancer-specific; its specificity ranges from 6% to 66%, so elevated results often lead to unnecessary biopsies.
• The Prostate Health Index improves accuracy in the 4–10 ng/mL gray zone; a Korean study using a cutoff of 22.9 found 90% sensitivity and 68.3% specificity.
• MRI has high negative predictive value (89%–95% for clinically significant cancer), but high cost and limited availability restrict it to high-risk patients or secondary use.
• DRE remains valuable in low-resource settings and high-risk populations; a normal DRE does not rule out cancer, and 84%–89% of low-risk tumors show no DRE abnormality.
• A multimodal approach is recommended: PSA or PHI for broad screening, DRE for physical assessment in high-risk patients, and MRI or PSMA-PET when precise imaging is needed and available.

Why Prostate Cancer Is a Growing Concern

Prostate cancer is a disease closely linked to aging and Western-style dietary habits. As Korea moves toward becoming a "super-aged" society (a population where a very large share of people are over 65), the importance of detecting prostate cancer early has grown sharply. This review, published in Investigative and Clinical Urology in 2025, set out to answer a simple question: with all the new diagnostic technology available, does the traditional digital rectal examination still matter?

The numbers explain why this question is urgent. In the United States, prostate cancer is projected to cause 35,250 deaths in 2024, making up 11% of all male cancer deaths. That ranks it as the second-leading cause of cancer-related death among American men. Prostate cancer is also the most frequently diagnosed male cancer in the US, with 299,010 new cases expected in 2024 — about 29% of all new male cancer diagnoses.

Korea faces a similar picture, though with some important differences. Data from 2020 showed 2,194 prostate cancer deaths in Korea — 4.3% of male cancer deaths, ranking seventh. The same year, Korea recorded 16,815 new cases — 12.9% of male cancers, ranking third. As the population continues to age, these numbers are expected to rise significantly.

One critical gap stands out: prostate cancer is not currently a mandatory component of Korea's national cancer screening program. Still, public awareness has grown, and more men are being tested during general health checkups. Many of these evaluations are triggered by lower urinary tract symptoms (LUTS) — problems like frequent urination, weak urine flow, or the urge to urinate at night. This increase in testing has put the spotlight on which diagnostic tools are most effective and cost-efficient.

PSA Blood Testing: Widely Used but Imperfect

The prostate-specific antigen (PSA) test is the most common blood test for prostate cancer. It measures the level of PSA, a protein produced by the prostate gland. The key point for patients to understand is that PSA is prostate-specific, but it is not cancer-specific. Elevated levels can also be caused by benign prostatic hyperplasia (BPH, a non-cancerous enlarged prostate) and prostatitis (inflammation of the prostate). This complicates the diagnostic process and can create anxiety when PSA levels rise.

How accurate is PSA testing? According to this review, its sensitivity (the ability to correctly identify men who actually have prostate cancer) ranges from 78% to 100%. But its specificity (the ability to correctly rule out cancer in men who do not have it) varies widely across studies, anywhere from 6% to 66%. In patients with lower urinary tract symptoms, PSA sensitivity was noted at 93%, but specificity dropped to just 20%. In plain terms: PSA testing catches most cancers, but it also produces many "false alarms."

The consequences of this low specificity are real. False positives lead to unnecessary biopsies — invasive procedures with risks that will be described shortly. That means additional costs for the healthcare system and unnecessary anxiety for patients. Still, PSA testing remains valuable because it is relatively inexpensive and widely available.

Doctors face a special challenge in what is called the "gray zone" of PSA levels — readings between 4 and 10 ng/mL. In this range, elevated PSA alone cannot reliably tell benign conditions from cancer, so deciding whether a biopsy is necessary becomes particularly difficult. In a typical prostate cancer diagnosis, a biopsy confirms the disease. Biopsies are performed either through the rectum (transrectal approach) or through the skin between the scrotum and anus (transperineal approach). Both approaches carry risks, including infection and urinary retention (the inability to empty the bladder).

To reduce unnecessary biopsies, doctors developed additional biomarkers. One is the ratio of free PSA (fPSA, PSA that circulates unbound in the blood) to total PSA, used to estimate cancer risk. However, its lower accuracy has led to declining use worldwide. In Korea specifically, the fPSA/PSA ratio is still used because the national health insurance system covers it, making it a cost-effective option. Another tool is PSA density (PSAD), which considers both prostate volume and PSA levels. PSAD has demonstrated improved specificity compared to PSA testing alone.

Current guidelines recommend combining PSA with DRE to predict prostate cancer. Notably, some studies suggest that DRE's prognostic value grows when PSA levels are elevated, but it is minimal when PSA is below 3 ng/mL.

The Prostate Health Index (PHI): Solving the Gray Zone Problem

The Prostate Health Index (PHI) was developed specifically to address PSA's limitations in the gray zone of 4–10 ng/mL. PHI is not a separate test — it is a calculated score that combines three measurements: total PSA, free PSA, and a specific PSA variant called [-2]proPSA. This combination enhances the ability to distinguish benign from malignant conditions within that tricky gray zone.

The numbers are encouraging. PHI demonstrates a sensitivity of approximately 79% and a specificity of 63%, offering better predictive accuracy than PSA alone. For clinically significant prostate cancer (csPCa — cancers that are likely to matter during a man's lifetime, as opposed to slow-growing tumors that may never cause symptoms), PHI's sensitivity reaches 87%, with a specificity of 57%.

A study conducted in Korea confirmed PHI's effectiveness in the gray zone. Using a cutoff value of 22.9, the test achieved a sensitivity of 90% and a specificity of 68.3%. For patients, that means PHI can correctly identify 9 out of 10 men with prostate cancer in this difficult diagnostic range.

What about cost? PHI testing is more expensive than a standard PSA test, but it remains far more affordable than an MRI. It also uses a simple blood draw, making it an easy test for patients and clinics alike. Because of its higher specificity, PHI is expected to reduce the number of unnecessary biopsies — a benefit for both patients and healthcare budgets.

MRI: High-Resolution Imaging Changes the Game

Magnetic resonance imaging (MRI) has revolutionized prostate cancer diagnosis. According to the landmark PROMIS study, MRI now plays a crucial role in assessing cancer risk, staging (determining how far the cancer has spread), and treatment planning. MRI provides high-resolution images of the tumor's location, size, and extent, which enhances diagnostic accuracy while avoiding the risks of invasive biopsy procedures.

How well does MRI perform? According to the PI-RADS (Prostate Imaging–Reporting and Data System) version 2.1, which standardizes how radiologists report MRI findings, prostate MRI demonstrates a sensitivity of 90%, a specificity of 62%, a positive predictive value (PPV — the chance that a positive result truly means cancer is present) of 53%, and a negative predictive value (NPV — the chance that a negative result truly means no cancer) of 93%. For clinically significant prostate cancer specifically, the NPV ranges from 89% to 95%.

That high NPV is critical. A negative MRI is highly reassuring: it means a man is very unlikely to harbor an aggressive, clinically significant cancer. This helps doctors avoid unnecessary biopsies and prevents the overdiagnosis of clinically insignificant prostate cancer — small, low-grade tumors that would probably never cause harm if left alone.

Two large European studies reinforced MRI's value. The MRI-FIRST study, conducted in France, examined multiparametric MRI (mpMRI — MRI that combines several types of imaging sequences) for detecting clinically significant prostate cancer. The study concluded that mpMRI before biopsy improves csPCa detection but does not eliminate the need for systematic biopsy — the two approaches play complementary roles. The PRECISION study similarly demonstrated that MRI-based targeted biopsy is not inferior to standard biopsy for detecting csPCa, while also reducing the overdiagnosis of clinically insignificant cancer.

Despite these strengths, MRI has major practical barriers. The high cost and limited availability of MRI machines restrict access, particularly in primary and secondary healthcare facilities. Incorporating MRI with PSA and DRE improves diagnostic accuracy, but MRI is not yet a feasible option for initial screening in most settings. It works best for confirming the presence of tumors and determining the need for a biopsy in patients at elevated risk. This is where DRE's role becomes particularly important — in high-risk populations or settings where MRI is not accessible.

PSMA-PET: A Powerful Tool with Practical Limits

Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is an emerging imaging technique that has not yet been approved as a screening test for prostate cancer in Korea. However, it is clinically significant for certain patients. By targeting PSMA, a protein found on prostate cancer cells, this imaging method provides precise visualization of cancer throughout the body.

PSMA-PET is mainly used in two groups of patients: those with biochemical recurrence (a rising PSA level after treatment for localized prostate cancer, suggesting the cancer may have returned) and those with high-risk prostate cancer. The evidence is strong: PSMA-PET provides superior diagnostic capabilities compared to traditional imaging methods such as computed tomography (CT), bone scan, and MRI, particularly in detecting minimal residual disease (tiny amounts of cancer left after treatment) and recurrent cancer.

Nevertheless, PSMA-PET is typically used as an adjunct (a supplementary tool) rather than a primary screening method. The reasons are practical: significant resource demands, the need for specialized nuclear medicine facilities, high cost, and limited accessibility. Several studies have explored whether PSMA-PET could replace other diagnostic tools, with encouraging outcomes. But the expense and access barriers make it unlikely that PSMA-PET will replace PSA or DRE as standard screening methods anytime soon.

Artificial Intelligence and Genetic Testing

Artificial intelligence (AI) is driving the development of innovative diagnostic approaches. Machine learning and deep learning algorithms (types of AI that learn patterns from large amounts of data) have been employed to increase the diagnostic accuracy of imaging and genomic data. The potential is enormous — AI can potentially spot subtle patterns that human eyes miss.

However, there are significant obstacles. The heterogeneity (variability) of AI models poses a challenge because medical research datasets tend to be small and imbalanced (for example, far more benign than cancerous images). These limitations make it difficult to develop AI systems that work reliably across different populations and clinical settings.

Genomic approaches take a different route. Researchers analyze human tissue samples to identify genetic mutations associated with prostate cancer. Although the precise mechanisms remain unclear, specific prostate cancer-related genes have been identified that are useful for diagnosis. These techniques are primarily used in patients with a family history of prostate cancer, where they help facilitate genetic counseling and personalized treatment strategies. Due to high costs, genomic testing is not yet feasible for routine screening.

Other Blood and Urine Biomarkers

Several additional blood and urine biomarkers have been developed, though none are yet approved as screening tests for prostate cancer in Korea. These tests aim to improve accuracy beyond what PSA alone can provide.

Blood-based biomarkers include:

• 4Kscore — combines total PSA, free PSA, intact PSA, and human kallikrein-2 (hK2, another protein produced by the prostate), while also incorporating age, DRE results, and previous biopsy outcomes into its risk calculation.
• IsoPSA — a test that detects cancer-specific structural isoforms (different molecular forms) of PSA, rather than just measuring PSA quantity.
• Stockholm3 — an algorithm-based test that integrates PSA, free PSA, intact PSA, hK2, MSMB (a protein linked to prostate cancer risk), MIC1 (a signaling protein), genetic polymorphisms (natural genetic variations), clinical variables, and PSA concentration.
• Proclarix — calculates a clinically significant prostate cancer risk score based on serum levels of THBS1, CTSD (two additional proteins), PSA, and percent free PSA, along with patient age.

Urine-based biomarkers include:

• PCA3 — a urine test that targets PCA3 messenger RNA, a genetic molecule that is overproduced in prostate cancer cells.
• SelectMDX — combines HOXC6 and DLX1 (two genes associated with prostate cancer) with clinical risk factors in a urine-based test.
• MiPS — targets PCA3 and TMPRSS2-ERG (a gene fusion common in prostate cancer) in urine.
• ExoDX — utilizes exosomal PCA3 and ERG RNA (genetic material contained in tiny particles shed by cells) for detection.

One practical detail matters here: with the exception of ExoDX, all urine-based tests require a DRE before the urine sample is collected. The prostate massage during DRE releases prostate cells into the urinary tract, improving test accuracy. If DRE use declines, these urine biomarkers may lose their diagnostic yield. Since these biomarkers are not approved for use in Korea, the review does not discuss them in detail — but they represent the future direction of prostate cancer diagnostics.

Digital Rectal Examination: The Traditional Exam Under Scrutiny

The digital rectal examination has long been a cornerstone of prostate cancer screening. During a DRE, the doctor inserts a gloved, lubricated finger into the rectum to feel the prostate gland through the rectal wall. The goal is to detect hard nodules, asymmetry, or irregular contours that might indicate cancer.

How accurate is DRE historically? Reported sensitivities range from 69% to 89%, with specificities from 84% to 98%, and positive predictive values from 25% to 35%. That PPV means that only about 1 in 4 to 1 in 3 men with an abnormal DRE actually has prostate cancer. In a European randomized trial for prostate cancer screening, the PPV of DRE in patients with PSA levels below 4 ng/mL was reported to range from just 4% to 33% — meaning that at low PSA levels, a suspicious DRE finding is frequently a false alarm.

Recent evidence has challenged DRE's accuracy more directly. A 2024 large-scale randomized trial showed that cancer detection rates with DRE were four times lower compared to PSA testing. Furthermore, 84% to 89% of low-risk tumors showed no abnormalities on DRE, indicating that the test may simply miss many early-stage cancers that would benefit from detection.

A recent systematic review (a rigorous summary of multiple studies) reported that DRE's sensitivity (51%) and specificity (41%) are lower than previously believed. Its PPV of 41% could actually lead to unnecessary biopsies — meaning more than half of men with abnormal DRE findings who undergo biopsy do not have cancer.

DRE has other limitations beyond accuracy. Reproducibility is a concern. One study involving 116 patients and eight examiners revealed significant discrepancies in diagnostic agreements among the examiners — meaning two different doctors examining the same patient often reached different conclusions. Patient discomfort is another issue. DRE can be painful or embarrassing, and this discomfort may outweigh its benefits as a routine screening tool.

Clinical staging provides a clearer picture of DRE's value. In the American Joint Committee on Cancer (AJCC) staging system, DRE results determine the T stage. This assessment differentiates between:

• T1: a non-palpable tumor (the doctor cannot feel it during DRE)
• T2: an organ-confined tumor (confined to the prostate and detectable by DRE)
• T3: a tumor extending beyond the prostate (the doctor can feel that it has spread beyond the gland's edge)

This staging serves as an initial step in determining disease severity and guiding treatment planning. Preoperatively, DRE can provide clinical insights into tumor size, location, and extracapsular extension (spread beyond the prostate capsule), aiding in surgical decision-making.

However, DRE's staging accuracy is imperfect. One study showed that between 20% and 40% of cases with negative DRE results (normal-feeling prostate) still exhibited extracapsular extension when the surgical pathology specimen was examined after prostate removal. Conversely, cases with positive DRE results (suspicious findings) showed extracapsular extension rates of 20% to 75% following surgery. This discrepancy between clinical staging and pathological findings means DRE can overestimate the stage in some cases and underestimate it in others.

Despite these shortcomings, many guidelines continue to recommend combining DRE with other diagnostic techniques. Why? For patients suspected of advanced prostate cancer, DRE may still be useful — a positive DRE finding has been linked to an increased risk of advanced disease. DRE is also reasonably accessible for low-income populations: it does not require expensive equipment, and it can be performed in any outpatient setting.

For patients, the takeaway is this: even if your DRE results are normal, it is advisable to consider additional tests based on factors such as family history, PSA levels, and age. A normal-feeling prostate does not rule out prostate cancer.

Balancing Strengths and Weaknesses: A Multimodal Approach

Each diagnostic method has unique strengths and limitations, which highlights the need for a multimodal approach to prostate cancer diagnosis. No single test is perfect, but used together, they provide a more complete picture.

PSA testing is cost-effective and widely accessible, but its low specificity creates a higher risk of overdiagnosis and unnecessary biopsies. Men who have a PSA test should understand that an elevated result does not automatically mean cancer — it means further evaluation is needed.

The Prostate Health Index improves diagnostic accuracy for patients with PSA levels in the gray zone. It is more expensive than PSA alone, but evidence suggests it effectively reduces false positives and unnecessary interventions. In a healthcare system like Korea's, which strives to balance cost and quality of care, this trade-off can be worthwhile.

MRI has significantly advanced the diagnostic landscape. It provides detailed anatomical insights that guide staging and biopsy procedures, and its ability to precisely locate tumors enhances the effectiveness of targeted biopsies, reducing overdiagnosis. However, due to high costs and limited availability, MRI should be reserved for high-risk patients or used as a secondary tool after initial assessments with PSA or PHI.

Emerging technologies like PSMA-PET and AI-powered diagnostics represent the next frontier. PSMA-PET has demonstrated superior accuracy in detecting minimal residual disease and recurrent cancer compared to traditional imaging. But the cost and the need for specialized nuclear medicine facilities make it impractical for routine screening today. AI-driven tools hold promise, but challenges such as data heterogeneity and the absence of standardized protocols must be resolved before widespread adoption is possible.

DRE remains valuable in specific contexts, especially in low-resource settings where access to advanced diagnostics is restricted. Although research has highlighted its variability and limitations, DRE's simplicity and cost-effectiveness continue to make it useful for initial screening. In regions like Korea — where there is a higher incidence of aggressive prostate cancer — DRE can still provide clinically valuable information for high-risk populations.

Korea's context is distinctive in two ways. First, a larger proportion of prostate cancer cases there are diagnosed at more advanced, higher-risk stages compared to regions like the United States. For these patients, DRE may offer real utility as a screening tool. Second, Korea's healthcare system is built on universal health insurance, which promotes cost-effective medical practices. This leads to less frequent use of expensive diagnostic tests for screening purposes. In this environment, DRE's low cost and wide availability make it an attractive component of the diagnostic toolkit.

Conclusions: What Should Patients Take Away?

Technological advances have introduced superior diagnostic alternatives, leading to reduced reliance on DRE among non-high-risk populations. Concerns about reproducibility and patient discomfort add weight to the argument against routine DRE screening.

Yet the authors make a crucial point: no country has completely eliminated the use of DRE. In Korea, where prostate cancer is frequently diagnosed at more aggressive stages, and where universal health insurance emphasizes cost efficiency, DRE retains value as part of a multimodal approach. It is an accessible, cost-effective tool — particularly valuable in low-resource settings or where advanced diagnostics are unavailable.

The authors conclude that it may be premature to dismiss DRE entirely. Instead, it should be considered part of a comprehensive diagnostic strategy tailored to the specific healthcare context and the population's risk profile. For patients, this means the ideal approach combines the strengths of multiple tools: PSA or PHI blood tests for broad screening, DRE for physical assessment in high-risk patients, and MRI or PSMA-PET when more precise imaging is needed and available.

Frequently Asked Questions

What is a digital rectal examination (DRE) and why is it done?

A DRE is a physical exam where a doctor inserts a gloved, lubricated finger into the rectum to feel the prostate through the rectal wall. It looks for hard nodules, asymmetry, or irregular contours that might suggest cancer. DRE also helps determine the T stage, which describes whether a tumor is non-palpable, confined to the prostate, or has spread beyond it.

How accurate is the PSA blood test for detecting prostate cancer?

PSA is prostate-specific but not cancer-specific; benign enlargement and inflammation can also raise it. Its sensitivity ranges from 78% to 100%, but specificity varies widely from 6% to 66%. In men with lower urinary tract symptoms, sensitivity was 93% but specificity only 20%. So PSA catches most cancers but also produces many false alarms, leading to unnecessary biopsies.

What does a PSA level between 4 and 10 ng/mL mean?

This range is called the gray zone. In it, an elevated PSA alone cannot reliably distinguish benign conditions from cancer, so deciding whether a biopsy is needed becomes difficult. The Prostate Health Index (PHI) was developed for this situation. In a Korean study using a cutoff of 22.9, PHI achieved 90% sensitivity and 68.3% specificity in the gray zone.

What are the risks of a prostate biopsy?

A biopsy confirms prostate cancer and is done either through the rectum (transrectal) or through the skin between the scrotum and anus (transperineal). Both approaches carry risks, including infection and urinary retention, which is the inability to empty the bladder. Because PSA testing has low specificity, many biopsies are performed in men who turn out not to have cancer.

How well does MRI detect prostate cancer, and who should have one?

According to PI-RADS version 2.1, prostate MRI has 90% sensitivity, 62% specificity, 53% positive predictive value, and 93% negative predictive value. For clinically significant cancer, negative predictive value is 89% to 95%, so a negative MRI is highly reassuring. However, high cost and limited availability mean MRI is reserved for high-risk patients or as a secondary tool.

If my DRE result is normal, can I still have prostate cancer?

Yes. A normal-feeling prostate does not rule out prostate cancer. In one study, 20% to 40% of cases with negative DRE results still showed extracapsular extension when the surgical specimen was examined. Also, 84% to 89% of low-risk tumors showed no abnormalities on DRE. Based on family history, PSA levels, and age, additional tests may still be advisable.

Why is DRE still used when newer tests like MRI exist?

No country has completely eliminated DRE. It is accessible, cost-effective, and needs no expensive equipment, so it remains useful in low-resource settings or where advanced imaging is unavailable. It is also valuable for high-risk populations, such as in Korea where prostate cancer is often diagnosed at more aggressive stages. Guidelines recommend combining DRE with other tests.

If my PSA is in the gray zone of 4 to 10 ng/mL and my doctor wants to do a biopsy, should I get a second opinion first?

PSA readings between 4 and 10 ng/mL cannot reliably separate benign enlargement or inflammation from cancer, so biopsy decisions in this range are genuinely difficult. The Prostate Health Index combines total PSA, free PSA, and [-2]proPSA, reaching about 79% sensitivity and 63% specificity, and a Korean study using a cutoff of 22.9 achieved 90% sensitivity and 68.3% specificity. A second opinion can help clarify whether additional testing before biopsy is appropriate. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Evaluating prostate cancer diagnostic methods: The role and relevance of digital rectal examination in modern era.

Authors: Chung Y, Hong SK.

Publication: Investigative and Clinical Urology 2025;66:181-187. Published online April 7, 2025. DOI: https://doi.org/10.4111/icu.20240456

This patient-friendly article is based on peer-reviewed research. The original article is an open-access review distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use with proper citation.