The randomized trials (PLCO, Goteborg-1, ERSPC) screened patients aged 50 to 69 years every 1 to 4 years and demonstrated a reduction in prostate cancer mortality. However, increasing evidence from additional analyses of the randomized trials, observational studies, and modeling studies show the balance between benefits (reduction in metastatic prostate cancer and prostate cancer mortality) and harms (anxiety, false positives, overdiagnosis, side-effects from prostate biopsy) of screening can be modulated through personalized risk-stratified screening approaches.33, 40, 60, 64-69 Risk-stratified re-screening intervals and biopsy thresholds may be tailored for select patients The re-screening interval can be 1 to 4 years for patients with PSA levels of 1 to 3 ng/mL between the ages of 45 to 70 years, while the re-screening interval can be prolonged for patients aged 45 to 70 years with a PSA < 1 ng/mL or those with a PSA below the age-specific median.59, 64, 70 Studies have shown that patients in the age range of 40 to 59 years with a PSA below the age-specific median, without a strong family history of prostate cancer, and no known pathogenic germline mutation, have a very low risk of metastatic cancer or long-term prostate cancer mortality. In a case-control study conducted in Sweden (Malmö Preventive Project cohort),40 among patients aged 40 to 55 years, the 15-year risk of metastasis for patients with PSA below the median at ages 45 to 49 years was 0.09%, and below the median at ages 51 to 55 years was 0.23%. In a U.S. case-control study (Physicians’ Health Study cohort)68 among patients 40 to 59 years, 82%, 71%, and 86% of lethal cases occurred in patients with PSA above the median at ages 40 to 49 years (median PSA 0.68 ng/mL), 50 to 54 years (median PSA 0.88 ng/mL), and 55 to 59 years (median PSA 0.96 ng/mL), respectively. Both studies suggest risk-stratified screening based on midlife PSA and should be considered in patients aged 45 to 59 years. However, they do not explicitly evaluate potential harm-benefit implications of any specific strategies. There were 2 models71 used to examine the impact of lengthening the interval between PSA tests to 8 years from a baseline interval of 2 years for patients with a PSA < 1.0 ng/mL at 45 years of age. Compared with biennial screening from ages 45 to 69 years, this risk-stratified approach led to half the number of tests while preserving more than 95% of the lives saved. Comparing 35 different screening strategies, a modeling study showed that PSA screening strategies using higher thresholds for biopsy referral for older patients, and screening patients with low PSA levels less frequently reduced the harms of screening (false positives, overdiagnoses) while saving the majority of lives with standard intervals (e.g., annual or biennial screening).33 Patients with low PSA Amongst patients 60 years of age with a PSA < 1 ng/mL (age-specific median), the 25-year risk of metastases or death from prostate cancer in a largely unscreened population (Malmö Preventive Project) is extremely low (0.5% and 0.2%, respectively).65 Although modeling data suggest a higher likelihood of death from prostate cancer if screening were discontinued in these patients (5% to 13.1% fewer lives saved compared with continuing screening to 69 years of age),71 the absolute number of lives saved by continuing screening is small; therefore, it may be reasonable to significantly lengthen the re-screening interval or discontinue screening based on SDM provided there are no other risk factors, such as strong family history of prostate cancer.60, 65, 71 In comparison of regularly screened patients in the Goteborg-1 trial versus unscreened people 60 years of age in the Malmö Preventive Project with PSA < 2 ng/mL, continued screening every 2 years for 15 years found an increase in prostate cancer incidence (7.7%) without a decrease in prostate cancer mortality.60 For patients with PSA ≥ 2 ng/mL, the reduction in cancer mortality for screened patients was large with 23 patients being screened (NNS) and 6 diagnosed (NND) to prevent 1 prostate cancer death at 15 years.60 In long-term follow-up from ERSPC, the actuarial probability of clinically significant prostate cancer at 16 years was 1.2% to 1.5% for patients aged 55 to 69 years with baseline PSA < 1.0 ng/mL, while for those initially screened at age 60 to 61 years with baseline PSA < 2 ng/mL, further continuation of screening is unlikely to be beneficial after the age of 68 to 70 years if PSA is still <2 ng/mL.72 Older patients The decision to screen patients should be an SDM conversation predicated upon a person’s prior PSA levels and general health. A flexible age to discontinue screening may be based on individualized decision-making to balance detection of aggressive cancers and overdiagnosis. This is particularly important in people between the ages of 70 to 80 years where there is a higher risk of competing mortality.73, 74 Clinicians may discontinue or substantially lengthen the re-screening interval for patients 75 years of age or older if PSA is < 3 ng/mL. In the Baltimore Longitudinal Study of Aging, patients 75 years or older with a PSA < 3 ng/mL were unlikely to be diagnosed with aggressive prostate cancer, and no patients between the ages of 75 to 80 years with a PSA < 3 ng/mL died of prostate cancer during their remaining lifetime.75 In ERSPC Rotterdam, patients aged 70 to 74 years who have previously undergone PSA-based screening without receiving a prostate cancer diagnosis had a cumulative incidence of prostate cancer-specific mortality of 0.54% (95% confidence interval [CI]: 0.40 to 0.70) in all patients, 0.11% (95% CI: 0.05 to 0.27) in patients with PSA < 2 ng/mL, and 0.85% (95% CI: 0.47 to 1.5) in patients with PSA 2 to 3 ng/mL, by age 85, suggesting that discontinuation of screening could be considered in patients with PSA < 3.0 ng/mL.76 A modeling study77 found that discontinuing screening at ages 66 and 72 years for patients with severe and moderate comorbidity, respectively, resulted in similar harms and benefits compared to screening people with average health to 74 years of age. Life expectancy In select patients who are very healthy with an estimated life expectancy of at least ten years, ongoing screening every two to four years is reasonable following SDM as these patients are more likely to benefit from therapeutic interventions, if indicated. However, for patients with less than a ten-year estimated life expectancy, screening is not likely to provide a benefit in terms of disease-specific or overall mortality. The 95% CI around the relative risk (RR) of prostate cancer mortality between the screening and control groups in ERSPC for patients aged 70 to 74 years excluded any benefit (RR: 1.18; 95% CI: 0.81 to 1.7).78 Furthermore, the evidence from randomized treatment trials comparing surgery, radiation, and monitoring has shown to have less benefit and more risk from curative treatment with increasing age.79-82 The risk in overdiagnosis of prostate cancer increases with increasing age.59, 74, 83, 84 Estimates of overdiagnosis also depend on the study population, design, and estimation methodology.85 Empirical estimates of overdiagnosis based on excess incidence from randomized screening trials are generally biased and overstate the long-term overdiagnosis risk.85 Risk calculators have been developed to estimate a patient’s life expectancy and can be informative during SDM. While a number of methods have been applied for estimating life expectancy, a simple approach is to use the social security life tables (<a href="https://www.ssa.gov/oact/STATS/table4c6.html">https://www.ssa.gov/oact/STATS/table4c6.html</a>). Based on current Social Security Administration (SSA) data, American patients older than 77 years of age have less than a 10-year life expectancy. The Michigan Urological Surgery Improvement Collaborative (MUSIC) has deployed a paper-based life expectancy tool that includes comorbidities (e.g., <a href="https://musicurology.com/wp-content/uploads/2022/02/Hawken_et_al-2017-BJU_International.pdf">https://musicurology.com/wp-content/uploads/2022/02/Hawken_et_al-2017-BJU_International.pdf</a>). Insurance companies are known to be particularly astute at estimating life expectancy and many have online calculators that include the use of tobacco, alcohol, physical activities, and comorbidities. For the purpose of estimating life expectancy, the use of these tools is likely more reliable than individual clinician judgment.86 The Panel notes most studies regarding baseline PSA have been conducted in populations of primarily White patients. The Southern Community Cohort Study (100% Black patients) showed that PSA levels in midlife were similar to those among White controls in prior studies and were strongly associated with risk of aggressive prostate cancer.67 Given the limitations in the range of evidence supporting screening intervals and for discontinuing screening, use of SDM is recommended to assist clinicians in tailoring the decision to each patient. The Agency of Healthcare Research and Quality (AHRQ) has developed a simple approach for SDM that addresses common clinician and patient level barriers called the SHARE approach.87 This approach recommends clinicians to Seek the patient’s participation, Help patients explore and compare options, Assess the patient’s values and preferences, Reach a decision together with the patient, and Evaluate the patient’s decision. The use of publicly available decision aids may be helpful in SDM, where available, and are updated to the most current level of evidence.