Prostate cancer is the fifth leading cause of male cancer-related deaths worldwide, counting 1,276,106 new cases and 358,989 deaths annually.[1] In the united states, it is the second leading cause of male-cancer related deaths, with about 165,000 new cases and 29,000 annual deaths.[2] According to the data from the National Cancer Institute, for an average American male, there is an 11 percent risk of being diagnosed with PCa over their lifetime( the incidence increasing with age) and a 2.5 % risk of dying from it. The median age of death due to prostate cancer is 80, with 75 % of the prostate cancer-specific deaths occurring in those above 75 years. The lifetime risk of dying from prostate cancer also varies in different ethnic groups, with African American men having the highest risk of 4.2 %. 

Being the most commonly diagnosed cancer in men does raise concerns for screening; however, most cases are slow-growing, which never becomes clinically evident, and data have suggested that many men die of other causes before cancer becomes advanced, thus making routine screening controversial.[3] There are different recommendations regarding when and whom to screen for prostate cancer—all of these measures incorporate PSA testing as the primary screening tool. Apart from subtle differences, the primary focus of all of these recommendations is to help the patient make an informed decision regarding whether or not to undergo screening after being explained the benefits and risks of screening as well as taking into consideration the patient's values and preferences in this decision making. 

EXPERT RECOMMENDATIONS FOR PROSTATE CANCER SCREENING.

 The U.S Preventive Services Task Force recommendations: 

• In men aged 55 to 69 years old, the decision to undergo periodic PSA screening should be an individual one after thorough upfront discussion between the physician and patient regarding risks, benefits, and limitations of such screening incorporating patient's values and preferences in decision making.
• It recommends against PSA screening in men 70 years and above as it offers minimal survival benefit, which does not outweigh the significant treatment side effects and morbidities.[4] American Cancer Society (ACS) Recommendations:

Asymptomatic men with less than a 10-year life expectancy must receive information about risks, benefits, and uncertainties associated with PCa screening before they can make an informed decision with their physician. 

• Average risk men should receive this information beginning at 50 years 

Men at high risk (e.g., those with a family history of prostate cancer, in particular, a first-degree relative diagnosed before 65 yrs of age or black men) should receive this information before 50 yrs.[5]

American Urologic Association (AUA) Recommendations:

• It recommends against PSA screening for men less than 40 years of age 
• It recommends against routine PSA screening for men 40 to 54 Yrs at average risk (for those under 55 Yrs of age having high risk, the decision regarding screening is on an individual basis.)
• For men aged 55 to 69 years, the decision to undergo screening must involve weighing the risk against the benefits. Hence, in this age group, there must be shared decision making taking into consideration the patient's values and preferences.
• For men who have made a shared decision with the provider and have agreed to go ahead with it, the routine screening interval must be of 2 years or more to reduce the harms of screening 

• It recommends against PSA screening in men +70 yrs or any men with a life expectancy of fewer than 10 to 15 years.[6]

American Academy of Family Physician (AAFP) Recommendations:

• It recommends against routine PSA screening. In men aged 55 to 69 years who consider undergoing periodic PSA testing should indulge in collaborative decision making regarding the risks and benefits of screening. 
• It recommends against screening for prostate cancer in men 70+ years.[7]

Canadian Task Force on Preventive health care recommends against PSA based screening for Prostate cancer. [8]

PSA AND ROLE OF OTHER ADJUNCTIVE PRE-BIOPSY TESTS.

PSA is a glycoprotein secreted by prostatic secretory epithelium and seminal vesicles and is the most abundant protein in seminal plasma. Some amount normally leaks into the blood. In case of any trauma or prostatic disease or any condition which disrupts the microarchitecture of the gland, PSA diffuses into extracellular space, which is then drained by the lymphatics into the bloodstream, thereby raising the PSA value in such men. Otherwise, the amount of PSA produced on per cell basis by malignant cells is less than normal prostatic cells or in benign prostatic hyperplasia. PSA level increases in malignant as benign conditions of the prostate like benign prostatic hyperplasia, prostatic inflammation or infection, perineal trauma, or sexual activity. Hence raised PSA level is not specific for prostate cancer. Furthermore, a normal PSA value does not rule out prostate cancer. Despite the lack of specificity, PSA remains the single most widely recruited test for early detection of prostate cancer. The normal value of PSA is considered to be less than or equal to 4 ng/ml. However, serum PSA levels increase with age, plus PSA levels rise at a faster rate in older men. Hence various age-specific ranges have been defined in an attempt to reduce the detection of less advanced tumors in the older age group and increase the detection of potentially curable tumors in the younger age group. These age-specific ranges are as follows[9]:

• 40 to 49 yrs: 0 to 2.5ng/ml
• 50 to 59 yrs: 0 to 3.5ng/ml
• 60 to 69 yrs: 0 to 4.5ng/ml 
• 70 to 79 yrs: 0 to 6.5ng/ml

Apart from age, studies have shown that certain medications also affect the value of PSA levels. A few of these are statins, thiazide diuretics, NSAIDs, 5-alpha-reductase inhibitors. All of them are known to decrease PSA levels.[10] Hence any rise in PSA levels while a patient is on these medications should raise the suspicion of prostate cancer. The clinician must keep this in mind before ignoring a normal PSA value. 

Apart from PSA, a digital rectal exam (DRE) is also sometimes used to aid screening, but it has low sensitivity and specificity. A DRE checks for the consistency, size, and texture of the prostate gland. An abnormal DRE is any nodularity, induration, or asymmetry.

WHEN TO BIOPSY?

After shared decision-making, a biopsy is usually indicated/justified when:

• Life expectancy is at least ten years ( some biopsy if life expectancy over five years) AND
• Two abnormal PSA values (more than the normally defined age-specific range) OR a PSA increase > 0.75ng/ml over one year OR palpable abnormality on DRE suggestive of cancer.[11]

For some older men or those having other co-morbidities with a raised PSA level, not pursuing a biopsy may be the appropriate decision when the patient's preference is in alignment with a less aggressive approach of further management. In case of an equivocal PSA value, a further urologic evaluation consisting of adjunctive PSA tests, imaging, and specific urine and blood-based molecular and genomic tests (like Prostate Health Index (PHI), 4K score, PCA3, SelectMDx, and EPI) may be useful in deciding on pursuing a biopsy.[12]

Although the widespread availability of PSA screening in 1992 did lead to an increase in the number of prostate cancers detected and a 44 % reduction in mortality as suggested by simulation models, calculations suggest that screening does not improve quality-adjusted life years (QALYs), even if there is a reduction in mortality.[13] For prostate cancer screening, there is a high potential for overdiagnosis. Overdiagnosis means screening of a condition that would not have been clinically evident in the lifetime of the patient. The prevalence of prostate cancer detection at autopsies of men that died due to other causes is higher than the lifetime incidence of prostate cancer in the population. Per data from studies, 23 to 50 % of prostate cancers are overdiagnosed.[14][15][16] Many of the screening-detected PCa are likely to have early-stage cancer, which probably wouldn’t have even caused any clinical problems in the patient’s lifetime. But this initial screening leads the patient to undergo further confirmatory testing and aggressive treatment. These, apart from causing a myriad of adverse effects, also bring in anxiety and cancer-related psychological effects for the patient.

The goal of screening is to reduce prostate cancer-specific morbidity and mortality by early detection of high-risk and localized cancers, which can be successfully treated. Screening has shown to offer a small potential reduction in the chance of dying from prostate cancer in some men.[4] Studies from RCT have demonstrated that in men aged 55 to 69 yrs, PSA based screening can prevent 1 PCa-related death when screened for over ten years per 1000 men screened.[17] Screening programs may prevent 3 cases of metastatic PCa per 1000 men screened.[4] But current results from screening trials show no reduction in the all-cause mortality.[18] There is inadequate evidence whether the benefits of screening are more in high-risk individuals aged 55 to 65 yrs and whether earlier screening of such high-risk men is beneficial. But for men aged 70+, there is adequate evidence consistent with no benefit of PSA-based screening for prostate cancer.[19]

For enhancing prostate cancer screening outcomes, an interprofessional team of specialty-trained nurses, general practitioners, physician assistants, urologists, and oncologists must work in coordination to deal with various issues that continue to challenge them in dealing with uncertainties regarding prostate cancer screening outcomes. Some of these include:

• Individualizing the evaluation of elevated PSA level
• Use of other tests to complement PSA in improving the diagnostic and prognostic accuracy
• Various uncertainties regarding when and how to use the newly available genomic tests at each stage of evaluation
• The current controversy regarding prostate cancer screening.
• Conflicting recommendation guidelines of different professional organizations for prostate cancer screening

This result is achievable by being updated with the new recommendations and information regarding screening for prostate cancer and effective collaboration and communication amongst the interdisciplinary team members. The interprofessional team can individualize the appropriate evaluation of each patient through communication and coordination of care. Specialty care nurses must work with the team for coordination of care and can aid in educating patients. [Level 5]

One of the major concerns regarding prostate cancer screening is overdiagnosis, which involves overtreatment of low-grade prostate cancer and decreasing the quality of life of the patient by adding treatment-associated side effects and psychological harm when in reality, cancer would not have caused any clinical problems in the patient. This outcome can be overcome by active surveillance (monitoring). Active surveillance is one of the management strategies in which a super select group of low-grade cancer patients are under close monitoring and followed through their disease course with the expectation to intervene only if cancer progresses.[20] This approach will lead to the avoidance of treatment-associated side effects in such patients. This monitoring is only achievable by cumulative efforts and coordination of care amongst the interdisciplinary team members.