Psa Prostate Cancer Screening Guidelines

National Comprehensive Cancer Network Recommendations

The NCCN guidelines for prostate cancer offer treatment recommendations for CRPC based on the presence or absence of distant metastases. For the most part, these recommendations are based on high-level evidence and are supported by uniform NCCN consensus .

CRPC without distant metastasis:

• Continue ADT to maintain castrate serum levels of testosterone
• For patients with PSA doubling time (PSADT < 10 months, monitoring is preferred, but other secondary hormone therapy may be used.
• For patients with PSADT 10 months, preferred regimens are apalutamide, darolutamide, or enzalutamide.

CRPC with distant metastasis:

• Biopsy of metastatic lesion, with tumor testing for MSI-high or dMMR and homologous recombination repair gene mutations , if not previously performed consider tumor mutational burden testing
• Continue ADT to maintain castrate levels of serum testosterone
• Additional treatment options are bone antiresorptive therapy with denosumab or zoledronic acid if bone metastases are present, palliative RT for painful bone metastases, and best supportive care.
• Further treatment varies, depending on whether the tumor is an adenocarcinoma or small cell/neuroendocrine prostate cancer

Systemic therapy for mCRPC adenocarcinoma

In patients with no prior docetaxel or novel hormone therapy, category 1 treatment recommendations are as follows:

In patients who have had prior docetaxel or novel hormone therapy, treatment recommendations are as follows:

• Cisplatin/etoposide

At What Age Should You Get Screened For Prostate Cancer

The following prostate cancer screening guidelines apply to men expected to live at least ten years.

Men ages 45 to 49 should have a baseline PSA test.

• If the PSA level is 3 ng / mL or higher, men should talk with their doctor about having a biopsy of the prostate.
• If the PSA level is between 1 and 3 ng / mL, men should see their doctor for another PSA test every two to four years.
• If the PSA level is less than 1 ng / mL, men should see their doctor for another PSA test between the ages of 51 and 55.

Men ages 50 to 59 should have their PSA level checked.

• If the PSA level is 3 ng / mL or higher, men should talk with their doctor about having a biopsy of the prostate.
• If the PSA level is between 1 and 3 ng / mL, men should see their doctor for another PSA test every two to four years.
• If the PSA level is less than 1 ng / mL, men should see their doctor for another PSA test at age 60.

Men ages 60 to 70 should have their PSA level checked.

• If the PSA level is 3 ng / mL or higher, men should talk with their doctor about having a biopsy of the prostate.
• If the PSA level is between 1 and 3 ng / mL, men should see their doctor for another PSA test every two to four years.
• If the PSA level is less than 1 ng / mL, no further screening is recommended.

Men ages 71 to 75 should talk with their doctor about whether to have a PSA test. This decision should be based on past PSA levels and the health of the man.

Recommendations On Screening For Prostate Cancer With The Prostate

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Prostate cancer is the most commonly diagnosed nonskin cancer in men and the third leading cause of cancer-related death among men in Canada.1 The current estimated lifetime risk of diagnosis is 14.3%, whereas the lifetime risk of death from prostate cancer is 3.6%.2 The prevalence of undiagnosed prostate cancer at autopsy is high and increases with age .3 Most cases of diagnosed prostate cancer have a good prognosis the 10-year estimated relative survival ratio is now 95%, the highest among all cancers in men.1

In Canada, the age-standardized rate of death from prostate cancer rose from 1969 to 1991, followed by a decline of 37.5% from 1992 to 2009, at an average rate of 2.6% per year . In 1990, the estimated age-standardized mortality was 30 cases per 100 000, and in 2010 it was just below 20 per 100 000.1 However, over the same period, the number of cases and the age-standardized incidence of prostate cancer both increased. Subsequent to the introduction and adoption of prostate-specific antigen testing, the incidence of prostate cancer increased rapidly from 1990 to a peak in 1993 and a second, less-pronounced peak in 2001 . Much of the excess incidence represents overdiagnosis,4,5 that is, the detection of cancers that would not progress to cause symptoms or death.6

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Special Types Of Psa Tests

The PSA level from a screening test is sometimes referred to as total PSA, because it includes the different forms of PSA . If you decide to get a PSA screening test and the result isnt normal, some doctors might consider using different types of PSA tests to help decide if you need a prostate biopsy, although not all doctors agree on how to use these tests. If your PSA test result isnt normal, ask your doctor to discuss your cancer risk and your need for further tests.

Percent-free PSA: PSA occurs in 2 major forms in the blood. One form is attached to blood proteins, while the other circulates free . The percent-free PSA is the ratio of how much PSA circulates free compared to the total PSA level. The percentage of free PSA is lower in men who have prostate cancer than in men who do not.

If your PSA test result is in the borderline range , the percent-free PSA might be used to help decide if you should have a prostate biopsy. A lower percent-free PSA means that your chance of having prostate cancer is higher and you should probably have a biopsy.

Many doctors recommend a prostate biopsy for men whose percent-free PSA is 10% or less, and advise that men consider a biopsy if it is between 10% and 25%. Using these cutoffs detects most cancers and helps some men avoid unnecessary biopsies. This test is widely used, but not all doctors agree that 25% is the best cutoff point to decide on a biopsy, and the cutoff may change depending on the overall PSA level.

Timelines For Prostate Screenings

All men should have prostate screenings, but the timeline for when you need a prostate screening varies based on different factors, including your age, ethnicity, medical and family history, previous screenings, and whether you have symptoms.

Your Urological Associates provider uses these factors to recommend the right prostate screening timeline for you. Generally, most men get their first prostate cancer screening between ages 45-55 and then have them based on the recommendation of their provider at regular intervals.

Your provider may order a screening earlier or more frequently if you develop symptoms of prostate cancer or an enlarged prostate, such as but not limited to:

• Waking up at night more than once to urinate
• Having frequent, urgent need to urinate
• Having blood in your urine
• Leaking urine before you getting to the bathroom
• Having issues emptying your bladder
• Dribbling urine after you go to the bathroom
• Erectile dysfunction
• Pain or burning when urinating

If you have any of these symptoms, dont wait to share them with your Urological Associates provider. Early detection of any prostate issues helps ensure early treatment, when its more effective.

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Response To Public Comment

A draft version of this recommendation statement was posted for public comment on the USPSTF website from April 11 to May 8, 2017. A number of comments suggested that because men are now living longer, they should be screened beyond 70 years of age. However, the USPSTF considered other evidence in addition to data on life expectancy when recommending against screening in men older than 70 years, including results from large screening trials that did not report a mortality benefit for men older than 70 years and evidence on the increased likelihood of harm from screening, diagnostic evaluation, treatment, overdiagnosis, and overtreatment. Several comments requested a recommendation for younger men and for baseline PSA-based screening in men 40 years and older or 50 years and older. The USPSTF found inadequate evidence that screening younger men or performing baseline PSA-based screening provides benefit.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Authors followed the policy regarding conflicts of interest described at . All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings.

Screening By Serum Psa

• Modeling the ERSPC combined with the PLCO Cancer Screening Trial

The prostate-specific antigen test has been examined in several observational settings for initial diagnosis of disease, as a tool in monitoring for recurrence after initial therapy, and for prognosis of outcomes after therapy. Numerous studies have also assessed its value as a screening intervention for the early detection of prostate cancer. The potential value of the test appears to be its simplicity, objectivity, reproducibility, relative lack of invasiveness, and relatively low cost. PSA testing has increased the detection rate of early-stage cancers, some of which may be curable by local-modality therapies, and others that do not require treatment. The possibility of identifying an excessive number of false-positive results in the form of benign prostatic lesions requires that the test be evaluated carefully. Furthermore, there is a risk of overdiagnosis and overtreatment . Randomized trials have therefore been conducted.

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How Patients Were Involved In The Creation Of This Article:

Three men eligible for PSA screening were full panel members. They identified important outcomes and led the discussion on values and preferences. They fully participated in the teleconferences and email discussions on the evidence and the recommendation. They also contributed to the identification of practical issues related to the decision to undergo PSA screening, and met all authorship criteria for the present article.

Absolute Benefits And Harms

The main infographic explains the recommendation and provides an overview of the absolute benefits and harms of screening at a 10 year time horizon for consistency and easier communication. However, the individual trials varied in their duration of follow-up from 10 to 20 years , and we used the relative estimates of effect, pooled in the linked systematic review, at the longest available follow-up time.1 For the 10 year time horizon, we used as baseline risk in the non-screening arm of the CAP trial. It provided the most contemporary estimates of risks from a large sample of men representative of a general practice setting.2

Death and cancer diagnosis

PSA screening may increase the detection of prostate cancer at 10 years), particularly of localised cancer ). But the data show no difference in prostate cancer mortality. Overall confidence in these estimates across these outcomes was low because of risk of bias as well as the inconsistency of findings across studies.

• When focusing on studies at lower risk of biasâERSPC trialsâthe panel was confident that over a 10 year period:

• PSA screening probably has little or no effect on death

• All-cause mortality )

• Prostate cancer mortality )

• Prostate cancer mortality is similar at longer periods of up to 18 years of follow-up 1

PSA screening probably increases diagnosis of prostate cancer

Detection of any prostate cancer )

Detection of localised cancer )

The panel was also confident that:

Quality of life

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Practical Issues And Other Considerations

Figure 3 outlines the key practical issues. PSA testing can be performed on any normal blood sample, but prostate biopsies and their follow-up have important implications for daily life.

Lower urinary tract symptoms are common complaints in adult men that can have a major impact on quality of life. Benign prostatic enlargement is the major cause. Evidence to date indicates that men with these complaints are not at increased risk of prostate cancer.4

For men who chose to undergo PSA testing, the optimal frequency of screening remains unknown. Figure 2 summarises the frequency used in the different trials, yet the accompanying systematic review did not find any significant subgroup effect of the effect of screening based on these different frequencies.1 Given that the ERSPC data are likely at lower risk of bias, PSA screening every four yearsârather than, say, every year or only once in a lifetimeâmay be the optimal interval.

Interpretation Of The Evidence

A major difference in interpretation of the evidence is whether or not the ERSPC and PLCO should be considered equally relevant with respect to the benefits of screening. The trials tested two different hypotheses as noted above screening versus no or little screening in the ERSPC and organized versus opportunistic screening in the PLCO. The latter interpretation of the PLCO trial is in line with statements in the PLCO publications.19,21 A modest effect of PSA screening versus none implies that a substantially larger study than PLCO is needed to meaningfully test more versus less frequent screening. Thus the PLCO was underpowered to address the question of organized versus opportunistic screening. The Panel interprets the randomized evidence to indicate that the ERSPC trial reflects the effect of PSA screening in a situation with low background screening.

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Linked Articles In This Bmj Rapid Recommendation Cluster

• Tikkinen KAO, Dahm P, Lytvyn L, et al. Prostate cancer screening with prostate-specific antigen test: a clinical practice guideline. BMJ 2018:362:k3581. doi:10.1136/bmj.k3581

• Summary of the results from the Rapid Recommendation process

Ilic D, Djulbegovic M, Jung JH, et al. Prostate cancer screening with prostate-specific antigen test: a systematic review and meta-analysis. BMJ 2018:362:k3519. doi:10.1136/bmj.k3519

Systematic review and meta-analysis of all available randomised trials that assessed PSA based screening for prostate cancer

Vernooij RWM, Lytvyn L, Pardo-Hernandez H, et al. Values and preferences of men for undergoing prostate-specific antigen screening for prostate cancer: a systematic review. BMJ Open 2018 0:e025470. doi:10.1136/bmjopen-2018-025470

Systematic review of the values and preference of men considering PSA screening

Expanded version of the results with multilayered recommendations, evidence summaries, and decision aids for use on all devices

How Is The Psa Test Used In Men Who Have Been Treated For Prostate Cancer

The PSA test is used to monitor men after surgery or radiation therapy for prostate cancer to see if their cancer has recurred . If a mans PSA level begins to rise after prostate cancer treatment, it may be the first sign of a recurrence. Such a biochemical relapse typically appears months or years before the recurrence causes symptoms.

However, a single elevated PSA measurement in someone who has a history of prostate cancer does not always mean that the cancer has come back. Someone who has been treated for prostate cancer should discuss an elevated PSA level with their doctor. The doctor may recommend repeating the PSA test or performing other tests to check for evidence of a recurrence. The doctor may look for a trend of rising PSA level over time rather than a single elevated PSA level.

A rising trend in PSA level over time in combination with other findings, such as an abnormal result on imaging tests, may lead the doctor to recommend further cancer treatment.

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Table 2 Evidence Profile For Mortality Outcomes

Outcome
Age 55-69, PSA every four years	0.80 ±	1 death fewer per 1,000 men screened	Moderate
Age 55-74, annual PSA screening for six years and DRE annually for four years	1.14	From 1 death fewer to 1 death more per 1,000 men screened	Low*

*The quality of evidence regarding prostate cancer-specific mortality derived from PLCO is low due to methodological limitations relating to the degree of contamination in the control arm. Therefore, PLCO does not provide a direct comparison of screening v. not screening. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41% to 46% for DRE.

± After a median follow-up of 11 years in the core age group, relative risk reduction 21% , and 29% after adjustment for contamination and noncompliance. Absolute risk reduction 1.07/ 1,000 screened.

European Society For Medical Oncology

The ESMO guidelines include the following treatment recommendations :

• Watchful waiting with delayed ADT for symptomatic progression is an option for men who are not suitable for, or are unwilling to have, radical treatment.
• Active surveillance is recommended for men with low-risk disease.
• Radical prostatectomy or radiation therapy is an option for men with low-risk disease not suitable for active surveillance, and is recommended for men with intermediate-risk disease.
• Primary ADT alone is not recommended as standard initial treatment for non-metastatic disease.
• External beam RT plus ADT is recommended for men with high-risk or locally advanced prostate cancer.
• RP plus pelvic lymphadenectomy is an option for selected men with high-risk disease.
• Men receiving radical RT for intermediate-risk disease should have short-course ADT for 4-6 months.
• Men receiving radical RT for high-risk disease should have long-course ADT .
• Neoadjuvant docetaxel chemotherapy may be offered before RT for young, fit men with very high-risk localized prostate cancer.
• Following RP, patients should have their serum PSA level monitored, with salvage RT recommended in the event of PSA failure.
• Adjuvant postoperative RT after RP is not routinely recommended.

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Investigations After Raised Psa

If PSA is raised, the test is usually repeated. Men with persistently elevated PSA levels typically undergo a transrectal, ultrasound-guided, core-needle biopsy of the prostate to test for prostate cancer . If cancer is detected in the biopsied tissue, management options include surgery, radiation therapy, hormonal treatment, active surveillance, or watchful waiting. Diagnostic imaging studies such as ultrasonography, magnetic resonance imaging , bone scan, and computed tomography, are often also performed, especially in men presenting with higher risk disease, to check for disease spread.