Prostate-Specific Antigen (PSA) screening for Prostate Cancer (PCa): Main recommendations Detección de antígeno prostático específico (PSA) para el cáncer de próstata (CaP): recomendaciones principales

Prostate cancer is the most frequent type of cancer diagnosed in men and is the second cause of cancer death in the United States. The widespread use of Prostate-Specific Antigen since the early 1990s has significantly increased its incidence. However, screening for prostate cancer remains one of the most controversial topics in the urologic literature. The latest clinical evidence suggests that screening does not affect all-cause mortality and has only a small effect on prostate-specific mortality. At the same time, there are risks associated with biopsy and prostate cancer treatment, such as urinary incontinence, infection, and erectile dysfunction. Current recommendations propose shared decision-making with the patient but differ, with respect to the appropriate ages for screening, as well as follow-up screening intervals.


Introduction
Prostate cancer is the most frequent solid cancer in men worldwide, which imposes a significant burden on health systems. Screening is one of the most controversial topics in the urologic literature due to uncertainty as to its benefits.
On the one hand, there is data that suggest that

Epidemiology of Prostate Cancer
According to the 2018 GLOBOCAN project, prostate cancer is the most frequently diagnosed cancer in 105 countries and is the fifth leading cause of cancer death in men. Particularly in the Sub-Saharan African countries and the Caribbean, it is the leading cause of cancer death in men. Its incidence in 2018 was 1,276,106 worldwide, accounting for 13.5% of all cancers in men, with 358,989 registered deaths, representing 3.8% of total cases. (1) In the United States, the estimated cancer statistics for 2020 are 191,930 new cases of prostate cancer, accounting for more than one in five new diagnoses.
Since the early 1990s, incidence has significantly increased. Accordingly, there has been a surge in the detection of asymptomatic disease due to widespread PSA testing, but it has stabilized in recent years. In the US, prostate cancer remains the second cause of cancer death, only after lung cancer. Nevertheless, it has the highest 5-year survival rate of all cancers, for all stages combined. (2) African Americans have the highest incidence and mortality rates. The risk of prostate cancer is 60% higher in that population than in Whites, and the mortality rate is twice as high, most likely due to social aspects, such as limited access to healthcare, and to genetic characteristics. Different genes with SNPs are implicated in increasing susceptibility to prostate cancer in African American men. (3) Regionally

History of Prostate-Specific Antigen
PSA is a protease belonging to the kallikrein family. It is secreted by epithelial cells and is also present in prostate cancer cells. Its function is to digest the gel formed by semenogelins after ejaculation, which explains why PSA serum levels are higher in prostate cancer. (7) It was first discovered in 1966 in semen, when Mitsuwo Hara, a Japanese forensic scientist, described the protein and suggested it could be used as a forensic tool in rape cases. The PSA blood test as the first-line screening tool was approved by the Food and Drug Administration (FDA) in the early 1990s. PSA derivatives (PSA velocity, PSA density, and the free-to-total PSA ratio) were also approved.
The 4.0 ng/ml limit for normal PSA levels, was first proposed in a 1986 study on a small population. Later, in 1991, a more extensive study led to FDA approval, when the efficacy of the cutoff for the 50-54 age group was assessed. Consequently, the limit of > 4.0 ng/ml was settled on for recommending biopsy. (9) The FDA also approved other PSA deri-

Prostate-Specific Antigen Screening: benefits and harms
Screening is defined as the presumptive identification of an unrecognized disease in an asymptomatic population, using tests, examinations, or procedures than can be easily applied. (11) For a prostate cancer screening test to be valuable, it must reduce morbidity and mortality, by identifying cases in an early stage, when treatment can be more effective. It should also identify risk factors that increase the probability of developing the disease. (12) As mentioned before, due to the widespread use of PSA screening, the incidence of prostate cancer has increased sharply. At the same time, mortality has declined, and incidence related to metastatic stage has significantly decreased in the past three decades. However, in some cases, increasing the detection of the disease can lead to subjecting the patient to the risks associated with treatment, and may not prolong life.
According to the ERSCP study, employing a PSA threshold of 3.0 ng/ml, for every 1000 men screened between 55 to 69 years of age, 720 will have a negative test.
Follow-up testing will not identify prostate cancer, and of the patients that undergo biopsy, four will have complications that require hospitalization. Out of 1000 men, 102 will be diagnosed with prostate cancer, but 33 of them will not become ill or die from the disease. Five men will die from prostate cancer, despite the screening. (13) The rate of complications associated with biopsy is about 2%, of which 0.8% are infectious complications. (14) Other complications include pain, bleeding, and urinary obstruction but it does not increase mortality. Additionally, no PSA threshold completely excludes prostate cancer, as shown in Table 1. (15)

Current recommendations about prostate cancer screening
We now describe the latest guideline recommendations, which still differ in many aspects, although they all emphasize shared decision-making and screening in well-informed men. screening. (17) In addition to discussing the risks and bene-  (Table 2). (20)

Conclusions
Prostate cancer screening continues to be a very controversial issue due to the lack of evidence supporting a decrease in morbidity and mortality. However, it is a public health problem, as it is the second cause of cancer death in the United States, and the most common cancer diagnosed in men worldwide.
There are still many differences between current guideline recommendations, especially with respect to patient ages for screening and whether risk factors should be taken into account for earlier screening. However, what the guidelines all have in common is that men undergoing screening must be well-informed, which means physicians must have sufficient knowledge about screening risks and benefits, to be able to discuss those issues with their patients.