Prostate cancer screening

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Prostate cancer screening
PurposeDetect prostate cancer (when no symptoms are present)

Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. [1] [2] When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early detection reduces mortality rates. [2]

Contents

Screening precedes a diagnosis and subsequent treatment. The digital rectal examination (DRE) is one screening tool, during which the prostate is manually assessed through the wall of the rectum. The second screening tool is the measurement of prostate-specific antigen (PSA) in the blood. The evidence remains insufficient to determine whether screening with PSA or DRE reduces mortality from prostate cancer. [1] A 2013 Cochrane review concluded PSA screening results in "no statistically significant difference in prostate cancer-specific mortality...". [3] The American studies were determined to have a high bias. European studies included in this review were of low bias and one reported "a significant reduction in prostate cancer-specific mortality." PSA screening with DRE was not assessed in this review. DRE was not assessed separately. [3]

Most recent guidelines have recommended that the decision whether or not to screen should be based on shared decision-making, [4] so that men are informed of the risks and benefits of screening. [5] [6] In 2012, the American Society of Clinical Oncology recommends screening be discouraged for those who are expected to live less than ten years, while for those with a longer life expectancy a decision should be made by the person in question. In general, they conclude that based on recent research, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment." [7]

Prostate biopsies are used to diagnose prostate cancer but are not done on asymptomatic men and therefore are not used for screening. [8] [9] Infection after prostate biopsy occurs in about 1%, while death occurs as a result of biopsy in 0.2%. [10] [11] Prostate biopsy guided by magnetic resonance imaging has improved the diagnostic accuracy of the procedure. [12] [13]

Prostate-specific antigen

Prostate-specific antigen PSA KLK3 PDB 2ZCK.png
Prostate-specific antigen

Prostate-specific antigen (PSA) is secreted by the epithelial cells of the prostate gland and can be detected in a sample of blood. [14] PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders. [15] PSA is not a unique indicator of prostate cancer, but may also detect prostatitis or benign prostatic hyperplasia. [16]

A 2018 United States Preventive Services Task Force (USPSTF) recommendation adjusted the prior opposition to PSA screening, [17] suggesting shared decision-making regarding screening in healthy males 55 to 69 years of age. [17] The recommendation for that age group states screening should only be done in those who wish it. [18] In those 70 and over, screening remains not recommended. [18]

Screening with PSA has been associated with a number of harms including over-diagnosis, increased prostate biopsy with associated harms, increased anxiety, and unneeded treatment. [19] The evidence surrounding prostate cancer screening indicates that it may cause little to no difference in mortality. [3]

On the other hand, up to 25% of men diagnosed in their 70s or even 80s die of prostate cancer, if they have high-grade (i.e., aggressive) prostate cancer. [20] Conversely, some argue against PSA testing for men who are too young, because too many men would have to be screened to find one cancer, and too many men would have treatment for cancer that would not progress. Low-risk prostate cancer does not always require immediate treatment, but may be amenable to active surveillance. [21] A PSA test cannot 'prove' the existence of prostate cancer by itself; varying levels of the antigen can be due to other causes. [22]

Digital rectal examination

During a digital rectal examination (DRE), a healthcare provider slides a gloved finger into the rectum and presses on the prostate, to check its size and to detect any lumps on the accessible side. If the examination suggests anomalies, a PSA test is performed. If an elevated PSA level is found, a follow-up test is then performed. [2]

A 2018 review recommended against primary care screening for prostate cancer with DRE due to the lack of evidence of the effectiveness of the practice. [23]

The USPSTF recommends against digital rectal examination as a screening tool due to lack of evidence of benefits. [24] Although DRE has long been used to diagnose prostate cancer, no controlled studies have shown a reduction in the morbidity or mortality of prostate cancer when detected by DRE at any age. [25] [26]

The American Urological Association in 2018 stated that for men aged 55 to 69, they could find no evidence to support the continued use of DRE as a first-line screening test; however, in men referred for an elevated PSA, DRE may be a useful secondary test. [27]

A study by Krilaviciute et al. (2023) [28] examined the effectiveness of the DRE as a standalone screening test for prostate cancer in >46,000 young men in Germany (age 45). It was found that DRE has a much lower detection rate for prostate cancer compared to PSA screening. Therefore, the authors recommend not to use DRE as a screening test for prostate cancer in young men, as it does not provide an improvement in detection compared to PSA screening.

Follow-up tests

Biopsy

Prostate biopsies are considered the gold standard in detecting prostate cancer. [8] [9] Infection after the biopsy procedure is a possible risk. [10] MRI guided techniques have improved the diagnostic accuracy of the procedure. [12] [13] Biopsies can be done through the rectum or perineum. [29] The biopsy technique includes factors such as needle angle and prostate mapping method. [30] People who have localized cancer and perineural invasion may benefit more from immediate treatment rather than adopting a watchful waiting approach. [30]

Ultrasound

Transrectal ultrasonography (TRUS) has the advantage of being fast and minimally invasive, and better than MRI for the evaluation of superficial tumor. [2] It also gives details about the layers of the rectal wall, accurate and useful for staging primary rectal cancer. While MRI is better in visualization of locally advanced and stenosing cancers, for staging perirectal lymph nodes, both TRUS and MRI are capable. TRUS has a small field of view, but 3D TRUS can improve the diagnosis of anorectal diseases. [31]

Magnetic Resonance Imaging

MRI is used when screening suggests a malignancy. [32] This model potentially minimizes unnecessary prostate biopsies while maximizing biopsy yield. [33] [ dubious – discuss ][ citation needed ] Despite concerns about the cost of MRI scans, compared to the long-term cost burden of the PSA/TRUS biopsy-based standard of care, the imaging model has been found to be cost-effective.[ dubious – discuss ][ citation needed ] MRI imaging can be used for patients who have had a previous negative biopsy but their PSA continues to increase. [34] Consensus has not been determined as to which of the MRI-targeted biopsy techniques is more useful. [35] In a study involving 400 men aged 50 – 69, MRI screening identified more men with prostate cancer than PSA tests or ultrasound and did not increase the number of men who needed a biopsy. [36] [37] A large-scale trial of MRI screening, TRANSFORM, began in the UK in spring 2024. [38]

Other imaging

68Ga-PSMA PET/CT imaging has become, in a relatively short period of time, the gold standard for restaging recurrent prostate cancer in clinical centers in which this imaging modality is available. [39] It is likely to become the standard imaging modality in the staging of intermediate-to-high risk primary prostate cancer. [39] The potential to guide therapy, and to facilitate more accurate prostatic biopsy is being explored. [39] In the theranostic paradigm, 68Ga-PSMA PET/CT imaging is critical for detecting prostate specific membrane antigen-avid disease which may then respond to targeted 177Lu-PSMA or 225Ac-PSMA therapies. [39] For local recurrence, 68Ga-PSMA PET/MR or PET/CT in combination with mpMR is most appropriate. [40] PSMA PET/CT may be potentially helpful for locating the cancer when combined with multiparametric MRI (mpMRI) for primary prostate care. [41] Prostate multiparametric MR imaging (mpMRI) is helpful in evaluating recurrence of primary prostate cancer following treatment. [42]

Other

A number of biomarkers (blood, urine and tissue based tests) for screening, diagnosing and determining the prognosis of prostate cancer are supported by evidence and used widely. [43] [44]

Researchers at the Korea Institute of Science and Technology (KIST) developed a urinary multi marker sensor with the ability to measure trace amounts of biomarkers from naturally voided urine. [48] The correlation of clinical state with the sensing signals form urinary multi markers was analyzed by two machine learning algorithms, random forest and neural network. Both algorithms provided a monotonic increase in screening performance as the number of biomarkers was increased. With the best combination of biomarkers, the algorithms were able to screen prostate cancer patients with more than 99% accuracy. [48]

Guidelines

Controversy

Screening for prostate cancer continues to generate debate among clinicians and broader lay audiences. [53] Publications authored by governmental, non-governmental and medical organizations continue the debate and publish recommendations for screening. [3] One in six men will be diagnosed with prostate cancer during their lifetime but screening may result in the overdiagnosis and overtreatment of prostate cancer. [54] [55] Though the death rates from prostate cancer continue to decline, 238,590 men were diagnosed with prostate cancer in the United States in 2013 while 29,720 died as a result. Death rates from prostate cancer have declined at a steady rate since 1992. Cancers of the prostate, lung and bronchus, and colorectum accounted for about 50% of all newly diagnosed cancers in American men in 2013, with prostate cancer constituting 28% of cases. Screening for prostate cancer varies by state and indicates differences in the use of screening for prostate cancer as well as variations between locales. Out of all cases of prostate cancer, African American men have an incidence of 62%. African American men are less likely to receive standard therapy for prostate cancer. This discrepancy may indicate that if they were to receive higher quality cancer treatment their survival rates would be similar to whites. [54]

Prostate cancer is also extremely heterogeneous: most prostate cancers are indolent and would never progress to a clinically meaningful stage if left undiagnosed and untreated during a man's lifetime. On the other hand, a subset are potentially lethal, and screening can identify some of these within a window of opportunity for cure. [56] Thus, PSA screening is advocated by some as a means of detecting high-risk, potentially lethal prostate cancer, with the understanding that lower-risk disease, if discovered, often does not need treatment and may be amenable to active surveillance. [21] [57]

Screening for prostate cancer is controversial because of cost and uncertain long-term benefits to patients. [58] Horan echos that sentiment in his book. [59] Private medical institutes, such as the Mayo Clinic, likewise acknowledge that "organizations vary in their recommendations about who should – and who shouldn't – get a PSA screening test." They conclude: "Ultimately, whether you should have a PSA test is something you'll have to decide after discussing it with your doctor, considering your risk factors and weighing your personal preferences." [60]

A 2009 study in Europe resulted in only a small decline in death rates and concluded that 48 men would need to be treated to save one life. But of the 47 men who were treated, most would be unable to ever again function sexually and would require more frequent trips to the bathroom. [59] [ page needed ] Aggressive marketing of screening tests by drug companies has also generated controversy as has the advocacy of testing by the American Urological Association. [59]

One commentator observed in 2011: “[I]t is prudent only to use a single PSA determination as a baseline, with biopsy and cancer treatment reserved for those with significant PSA changes over time, or for those with clinical manifestations mandating immediate therapy..... absolute levels of PSA are rarely meaningful; it is the relative change in PSA levels over time that provides insight, but not definitive proof of a cancerous condition necessitating therapy.“ [61]

Men report low levels of distress surrounding PSA screening. [62] Men who present for PSA or have PSA levels at baseline scored low on cancer distress on numerous scales. [62]

History

Global comparisons of prostate cancer screening Prostate cancer global epidemiology.png
Global comparisons of prostate cancer screening

Screening of PSA began in the 1990s. In the European Randomized Study of Screening for Prostate Cancer (ERSPC) initiated in the early 1990s, the researchers concluded that PSA-based screening did reduce the rate of death from prostate cancer but created a high risk of overdiagnosis, i.e., 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent just one death from prostate cancer within 9 years. [63]

A study published in the European Journal of Cancer (October 2009) documented that prostate cancer screening reduced prostate cancer mortality by 37 percent. By utilizing a control group of men from Northern Ireland, where PSA screening is infrequent, the research showed this substantial reduction in prostate cancer deaths when compared to men who were PSA tested as part of the ERSPC study. [64]

A study published in the New England Journal of Medicine in 2009 found that over a 7 to 10-year period, "screening did not reduce the death rate in men 55 and over." [59] Former screening proponents, including some from Stanford University, have come out against routine testing. In February 2010, the American Cancer Society urged "more caution in using the test." And the American College of Preventive Medicine concluded that "there was insufficient evidence to recommend routine screening." [59]

A further study, the NHS Comparison Arm for ProtecT (CAP), as part of the Prostate testing for cancer and Treatment (ProtecT) study, randomized GP practices with 460,000 men aged 50–69 at centers in 9 cities in Britain from 2001–2005 to usual care or prostate cancer screening with PSA (biopsy if PSA ≥ 3). [65] The "Comparison Arm" has yet to report as of early 2018. [66]

See also

Related Research Articles

<span class="mw-page-title-main">Prostate cancer</span> Male reproductive organ cancer

Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of prostate tissue is usually detected through screening tests, typically blood tests that check for prostate-specific antigen (PSA) levels. Those with high levels of PSA in their blood are at increased risk for developing prostate cancer. Diagnosis requires a biopsy of the prostate. If cancer is present, the pathologist assigns a Gleason score, and a higher score represents a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. A higher stage signifies a more advanced, more dangerous disease.

<span class="mw-page-title-main">Benign prostatic hyperplasia</span> Noncancerous increase in size of the prostate gland

Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.

<span class="mw-page-title-main">Prostate-specific antigen</span> Mammalian protein found in humans

Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland in men and the paraurethral glands in women.

<span class="mw-page-title-main">Prostate biopsy</span> Medical test

Prostate biopsy is a procedure in which small hollow needle-core samples are removed from a man's prostate gland to be examined for the presence of prostate cancer. It is typically performed when the result from a PSA blood test is high. It may also be considered advisable after a digital rectal exam (DRE) finds possible abnormality. PSA screening is controversial as PSA may become elevated due to non-cancerous conditions such as benign prostatic hyperplasia (BPH), by infection, or by manipulation of the prostate during surgery or catheterization. Additionally many prostate cancers detected by screening develop so slowly that they would not cause problems during a man's lifetime, making the complications due to treatment unnecessary.

A gallium scan is a type of nuclear medicine diagnostic investigation that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. The gamma emission of gallium-67 is imaged by a gamma camera, while the positron emission of gallium-68 is imaged by positron emission tomography (PET). Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Radioactive gallium(III) is rapidly bound by transferrin, wich then preferentially accumulates in tumors, inflammation, and both acute and chronic infection, allowing these pathological processes to be imaged. Gallium is particularly useful in imaging osteomyelitis that involves the spine, and in imaging older and chronic infections that may be the cause of a fever of unknown origin. Due to lack of disease specificity, imaging with radioactive gallium(III) salts or simple complexes thereof, such as 67Ga-citrate, has gradually become less important over time and is rarely used these days.

Early prostate cancer antigen-2 (EPCA-2) is a protein of which blood levels are elevated in prostate cancer. It appears to provide more accuracy in identifying early prostate cancer than the standard prostate cancer marker, PSA.

<span class="mw-page-title-main">Glutamate carboxypeptidase II</span> Enzyme

TAH molecule, also known as N-acetyl-L-aspartyl-L-glutamate peptidase I, NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa.

Lower urinary tract symptoms (LUTS) refer to a group of clinical symptoms involving the bladder, urinary sphincter, urethra and, in men, the prostate. The term is more commonly applied to men – over 40% of older men are affected – but lower urinary tract symptoms also affect women. The condition is also termed prostatism in men, but LUTS is preferred.

<span class="mw-page-title-main">PCA3</span> Non-coding RNA in the species Homo sapiens

Prostate cancer antigen 3 is a gene that expresses a non-coding RNA. PCA3 is only expressed in human prostate tissue, and the gene is highly overexpressed in prostate cancer. Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.

Douglas S. Scherr is an American surgeon and specialist in Urologic Oncology. He is currently the Clinical Director of Urologic Oncology at Weill Cornell Medicine. He also holds an appointment at the Rockefeller University as a Visiting Associate Physician. Scherr was the first physician at Cornell to perform a robotic prostatectomy as well as a robotic cystectomy.

<span class="mw-page-title-main">Cancer screening</span> Method to detect cancer

The objective of cancer screening is to detect cancer before symptoms appear, involving various methods such as blood tests, urine tests, DNA tests, and medical imaging. The purpose of screening is early cancer detection, to make the cancer easier to treat and extending life expectancy. In 2019, cancer was the second leading cause of death globally; more recent data is pending due to the COVID-19 pandemic.

Treatment for prostate cancer may involve active surveillance, surgery, radiation therapy – including brachytherapy and external-beam radiation therapy, proton therapy, high-intensity focused ultrasound (HIFU), cryosurgery, hormonal therapy, chemotherapy, or some combination. Treatments also extend to survivorship based interventions. These interventions are focused on five domains including: physical symptoms, psychological symptoms, surveillance, health promotion and care coordination. However, a published review has found only high levels of evidence for interventions that target physical and psychological symptom management and health promotion, with no reviews of interventions for either care coordination or surveillance. The favored treatment option depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors include the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.

William K. Oh, is an American medical oncologist, academic leader and expert in the management of prostate cancer. He has also held leadership roles in industry and non-profits, including as Chair of the American Cancer Society’s National Prostate Cancer Roundtable.

Active surveillance is a management option for localized prostate cancer that can be offered to appropriate patients who would also be candidates for aggressive local therapies, with the intent to intervene if the disease progresses. Active surveillance should not be confused with watchful waiting, another observational strategy for men that would not be candidates for curative therapy because of a limited life expectancy.

Andrew Julian Vickers is a biostatistician and attending research methodologist at Memorial Sloan Kettering Cancer Center. Since 2013, he has also been professor of public health at Weill Cornell Medical College. He is the statistical editor for the peer-reviewed journal European Urology.

PI-RADS is an acronym for Prostate Imaging Reporting and Data System, defining standards of high-quality clinical service for multi-parametric magnetic resonance imaging (mpMRI), including image creation and reporting.

A PSMA scan is a nuclear medicine imaging technique used in the diagnosis and staging of prostate cancer. It is carried out by injection of a radiopharmaceutical with a positron or gamma emitting radionuclide and a prostate-specific membrane antigen (PSMA) targeting ligand. After injection, imaging of positron emitters such as gallium-68 (68Ga), copper-64 (64Cu), and fluorine-18 (18F) is carried out with a positron emission tomography (PET) scanner. For gamma emitters such as technetium-99m (99mTc) and indium-111 (111In) single-photon emission computed tomography (SPECT) imaging is performed with a gamma camera.

Caroline M. Moore is the first woman to be made a professor of urology in the United Kingdom. She works in the diagnosis and treatment of prostate cancer at University College London.

Declan G. Murphy, FRACS, FRCS, is a urologist, director of the unit for genitourinary oncology and robotic surgery at the Peter MacCallum Cancer Centre in Melbourne, Australia, professor at the Sir Peter MacCallum Department of Oncology at the University of Melbourne, and associate editor of the British Journal of Urology International. In 2010 he introduced robotic surgery for urology to the public sector health services in Victoria, Australia.

Gallium (<sup>68</sup>Ga) gozetotide Radiopharmaceutical medication

Gallium (68Ga) gozetotide or Gallium (68Ga) PSMA-11 sold under the brand name Illuccix among others, is a radiopharmaceutical made of 68Ga conjugated to prostate-specific membrane antigen (PSMA) targeting ligand, Glu-Urea-Lys(Ahx)-HBED-CC, used for imaging prostate cancer by positron emission tomography (PET). The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.

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