When to Treat Elevated PSA Results
Treatment decisions for elevated PSA depend critically on the clinical context: initial screening versus post-treatment surveillance, with immediate action required for PSA >4.0 ng/mL with abnormal digital rectal examination, PSA velocity ≥1.0 ng/mL/year, or post-treatment biochemical recurrence. 1
Initial Elevated PSA (Screening Context)
Immediate Referral Criteria
- Refer immediately to urology without waiting for repeat testing if: 1
Confirmation and Workup for PSA 4.0-50 ng/mL
- Confirm isolated elevated PSA with repeat testing 6-8 weeks later before proceeding with invasive workup, allowing resolution of transient elevations from manipulation, inflammation, or infection 3
- Exclude confounding factors: 1
- Active urinary tract infection or prostatitis (can dramatically elevate PSA; retest 6-8 weeks after completing antibiotics)
- Recent ejaculation, physical activity, or prostate manipulation (wait minimum 6-8 weeks after substantial manipulation)
- Use of 5-alpha reductase inhibitors (finasteride/dutasteride reduce PSA by ~50% within 6 months; any confirmed increase from lowest value while on these medications may signal cancer even if levels remain "normal") 4
- Use the same laboratory and assay for all measurements to minimize 20-25% variability between different assays 3
Risk Stratification After Confirmation
- Calculate PSA density (PSA ÷ prostate volume): one of the strongest predictors for clinically significant cancer 1
- Order multiparametric MRI before biopsy in most cases (high sensitivity for clinically significant cancer, guides targeted biopsies, reduces detection of insignificant cancers) 1
- For PSA 4-10 ng/mL, consider additional biomarkers: 1
- Percent free PSA: <10% suggests higher cancer risk, >25% suggests benign disease
- Phi score >35 or 4Kscore for further risk stratification
- Approximately 30-35% of men with PSA 4-10 ng/mL will have cancer on biopsy
Critical Pitfall: Antibiotics Have No Role
- Do not give empiric antibiotics for asymptomatic elevated PSA: approximately 2 of 3 men with elevated PSA do not have prostate cancer, and empiric antibiotics have little value for improving test performance in asymptomatic men 1, 5
- Antibiotics are only indicated for confirmed urinary tract infection or prostatitis with symptoms
When NOT to Treat (Surveillance Appropriate)
- If repeat PSA normalizes (<4.0 ng/mL), continue surveillance with PSA testing at 2-4 year intervals 1, 3
- Men aged 60 years with PSA <1.0 ng/mL have very low risk of metastases or death from prostate cancer and may require less frequent monitoring 1
- Men with PSA 10-20 ng/mL but PSA density <0.15 ng/mL/g have outcomes similar to low-risk disease and active surveillance may be appropriate 6
Post-Treatment Rising PSA (Biochemical Recurrence)
Definition of Biochemical Recurrence
- Post-radical prostatectomy: PSA ≥0.4 ng/mL rising on three occasions ≥2 weeks apart (all values should be ≥0.20 ng/mL and follow rising trend) 1, 3
- Post-radiation therapy: minimum of three PSA determinations ≥2 weeks apart, with minimum value >1.5 ng/dL at enrollment 1
When Rising PSA Triggers Treatment
Active Surveillance Patients:
- Rising PSA or adverse PSA doubling time/velocity should trigger further investigation with a view to active treatment 7
- Monitor in framework of standardized protocol 7
Watchful Waiting Patients:
- Commencement of hormonal therapy should be led by development of symptoms rather than PSA alone 7
- Exception: patients at high risk of complications or rapid progression (baseline PSA >50 ng/mL and/or PSA doubling time <12 months) should receive treatment based on PSA 7
Post-Radical Prostatectomy:
- Routine PSA determination is necessary to demonstrate biochemical failure early, because early salvage radiotherapy can reduce mortality 7
- Early hormonal therapy is not routinely advised for PSA relapse but is an option for those with short PSA doubling time 7
Post-Radiation Therapy:
- Intermittent androgen deprivation can be offered to patients starting salvage androgen deprivation for rising PSA >1 year following radiotherapy 7
- Optimal treatment of biochemical relapse after radiotherapy is not well established; radical local salvage treatments may induce considerable toxicity 7
Required Workup Before Treatment
- Exclude metastatic disease with CT (or MRI) and bone scan (bone scan generally unnecessary if PSA <20 ng/mL unless symptoms suggest bone involvement) 1
- Measure testosterone levels: should be ≥150 ng/dL, and patient should not be receiving hormonal therapy for minimum 1 year 1
- Consider PSMA-PET/CT if available for higher sensitivity in detecting metastases 1
- Obtain minimum of 3 PSA measurements over 3 months with at least 4 weeks between measurements to calculate PSA doubling time and assess disease progression 3
Special Considerations
PSA Kinetics
- PSA kinetics (velocity, doubling time) has no role in selecting men for initial biopsy 7
- However, PSA velocity ≥1.0 ng/mL/year warrants immediate referral regardless of absolute PSA value 1
Clinical Factors
- Age, symptoms, family history, comorbidity, digital rectal examination, and transrectal ultrasound findings should all be used in the decision whether to biopsy 7
- Risk calculators and nomograms can improve efficiency in selecting men for biopsy 7