Prostate cancer screening


Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. 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.
Screening precedes a diagnosis and subsequent treatment. The digital rectal examination 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 in the blood. The evidence remains insufficient to determine whether screening with PSA or DRE reduces mortality from prostate cancer. A 2013 Cochrane review concluded PSA screening results in "no statistically significant difference in prostate cancer-specific mortality...". 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.
Guidelines generally recommend that the decision whether or not to screen should be based on shared decision-making, so that men are informed of the risks and benefits of screening. 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."
Prostate biopsies are used to diagnose prostate cancer but are not done on asymptomatic men and therefore are not used for screening. Infection after prostate biopsy occurs in about 1%, while death occurs as a result of biopsy in 0.2%. Prostate biopsy guided by magnetic resonance imaging has improved the diagnostic accuracy of the procedure.

Prostate-specific antigen

is secreted by the epithelial cells of the prostate gland and can be detected in a sample of blood. 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. PSA is not a unique indicator of prostate cancer, but may also detect prostatitis or benign prostatic hyperplasia.
A 2018 United States Preventive Services Task Force draft adjusted the prior opposition to PSA screening. It suggests shared decision-making regarding screening in healthy males 55 to 69 years of age. The final recommendation for that age group states screening should only be done in those who wish it. In those 70 and over, screening remains not recommended.
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.
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 prostate cancer. 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. A PSA test cannot 'prove' the existence of prostate cancer by itself; varying levels of the antigen can be due to other causes.

Digital rectal examination

During a digital rectal examination, 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.
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.
The USPSTF recommends against digital rectal examination as a screening tool due to lack of evidence of benefits. 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.
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.

Follow-up tests

Biopsy

are considered the gold standard in detecting prostate cancer. Infection is a possible risk. MRI guided techniques have improved the diagnostic accuracy of the procedure. Biopsies can be done through the rectum or penis.

Ultrasound

has the advantage of being fast and minimally invasive, and better than MRI for the evaluation of superficial tumor. 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.

Magnetic imaging

MRI imaging is used when screening suggests a malignancy. This model potentially minimizes unnecessary prostate biopsies while maximizing biopsy yield. 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. MRI imaging can be used for patients who have had a previous negative biopsy but their PSA continues to increase. Consensus has not been determined as to which of the MRI-targeted biopsy techniques is more useful.

Other imaging

-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. It is likely to become the standard imaging modality in the staging of intermediate-to-high risk primary prostate cancer. The potential to guide therapy, and to facilitate more accurate prostatic biopsy is being explored. 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. For local recurrence, 68Ga-PSMA PET/MR or PET/CT in combination with mpMR is most appropriate. PSMA PET/CT may be potentially helpful for locating the cancer when combined with multiparametric MRI for primary prostate care. Prostate multiparametric MR imaging is helpful in evaluating recurrence of primary prostate cancer following treatment.

Other

A number of biomarkers for prostate cancer exist. These include:
From population screening to early diagnosis there is a lack of understanding. Screening for prostate cancer continues to generate debate by clinicians and broader lay audiences. Publications authored by governmental, non-governmental and medical organizations continue the debate and publish recommendations for screening. 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. Though the death rates from prostate cancer continue to decline, 238,590 men were diagnosed with prostate cancer 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 account for about 50% of all newly diagnosed cancers in men. Prostate cancer alone constitutes 28% cases in men. 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 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.
Prostate cancer is also extremely heterogeneous: many, perhaps 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. Thus, the concept of 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.
Screening for prostate cancer is controversial because of cost and uncertain long-term benefits to patients. Horan echos that sentiment in his book.
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."
A 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. Aggressive marketing of screening tests by drug companies has also generated controversy as has the advocacy of testing by the American Urological Association.
One commentator has observed: “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.“

History

Screening of PSA began in the 1990s. In the European Randomized Study of Screening for Prostate Cancer 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.
A study published in the European Journal of Cancer 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.
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." 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."
A further study, the NHS Comparison Arm for ProtecT, as part of the Prostate testing for cancer and Treatment 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. The "Comparison Arm" has yet to report as of early 2018.