Rationale and impact
This section briefly explains why the committee made the recommendation and how it might affect practice.
The evidence on the diagnostic accuracy of fixed and age-specific prostate-specific antigen (PSA) thresholds was very uncertain because all of the studies were based on a population that had already been referred to secondary care. The 2019 guideline recommended referral if PSA levels were above the age-specific reference range. The committee agreed that referral should be considered based on PSA thresholds, but did not make a stronger recommendation because of the uncertainty in the evidence and the likely low positive predictive value of the PSA test for prevalence estimates based on UK population data. The committee noted that many prostate cancers are slow growing and might never impact a person's life expectancy. Some people might choose not to be referred to secondary care to avoid invasive investigations and treatment that might not benefit them. Therefore, the committee agreed that a patient-centred approach to referral is important, and recommended that the person's preferences and any comorbidities should be taken into account.
The committee agreed that more research is needed in this area to better understand the most appropriate thresholds that should prompt referral to secondary care for each age group. The committee noted that ethnicity and family history are important factors that affect the risk of prostate cancer. Therefore, they recommended that the data from research be stratified by these factors to determine whether different PSA levels should prompt referral in these groups. Research in this area may also help to address health inequalities in prostate cancer diagnosis and outcomes in the UK.
There was no strong evidence to differentiate between using age-specific or fixed PSA thresholds. The committee also noted that no cost-effectiveness evidence comparing age-specific thresholds with fixed thresholds was identified. However, because PSA levels increase naturally with age, the committee agreed a lower fixed PSA threshold would detect more cases of prostate cancer but also lead to unnecessary biopsies and overtreatment in some age groups. This would also be likely to result in more referrals to secondary care and have a significant impact on NHS resources. The committee therefore recommended the use of age-specific thresholds, which are already established in current practice and were recommended in the previous version of the guideline. Because of regional variations in practice (particularly in the 50 to 69 age range), the committee decided to define the age-specific PSA thresholds. The committee agreed that the thresholds used in the reviewed studies on people with symptoms of possible prostate cancer should be used in the absence of evidence to support alternative values, because these studies were most applicable to the population that the recommendation applies to. No evidence was available specifically for people under 40 or over 79, and so the committee recommended that clinical judgement is used when deciding whether to refer people in these groups to secondary care.
Referral based on age-specific PSA thresholds is already recommended, so practice should not change significantly. Also, clarifying the age-specific thresholds will help standardise care. Taking into account patient preferences and comorbidities should also lead to a more patient-centred approach to referral.