Management of PSA 28 ng/mL
A PSA of 28 ng/mL requires immediate urological referral and comprehensive staging workup, as this level carries high probability of prostate cancer with significant risk of metastatic disease. 1
Immediate Diagnostic Workup
Essential Initial Steps
Perform digital rectal examination (DRE) to assess for nodules, asymmetry, or increased firmness, which would further confirm suspicion for malignancy regardless of PSA level 1
Order bone scan immediately - at PSA >20 ng/mL, bone scan is indicated to evaluate for metastatic disease, as the probability of bone metastases increases substantially at this level 2, 1
Obtain CT or MRI of pelvis for staging, as radiographic imaging is generally indicated when PSA exceeds 20-25 ng/mL to assess for lymphadenopathy and local extension 2
Consider PSMA-PET/CT if available for higher sensitivity in detecting metastases compared to conventional imaging 3, 1
Tissue Diagnosis
Proceed directly to transrectal ultrasound-guided prostate biopsy with at least 10-12 core samples without waiting for MRI, as PSA >50 ng/mL represents high-risk disease where direct biopsy is appropriate 3, 1
Multiparametric MRI can be obtained but should not delay biopsy at this PSA level, though it may help identify extent of disease 1
Measure serum testosterone level to ensure it is ≥150 ng/dL and confirm the patient is not receiving hormonal therapy, as androgen suppression affects PSA interpretation 2, 1, 4
Risk Stratification Context
At PSA 28 ng/mL, the patient falls into a high-risk category where:
Approximately 50% of men with PSA >10 ng/mL will have cancer recurrence within 10 years even after definitive treatment 2
The risk of biochemical failure increases approximately 2-fold for each 2-point increase in PSA level 2
Extended pelvic lymph node dissection should be strongly considered at time of surgery if radical prostatectomy is pursued, as lymph node involvement probability is substantial 2
Important Caveats
Rule Out Confounding Factors
Exclude active prostatitis or urinary tract infection, as these can dramatically elevate PSA and should be treated first with reassessment in 2-4 weeks 1
Assess for recent prostate manipulation (biopsy, cystoscopy, catheterization) or ejaculation within 48 hours, which can transiently elevate PSA 1
If patient is on finasteride or dutasteride, recognize that PSA should be reduced by approximately 50% within 6 months of treatment; any confirmed increase from the lowest PSA value while on these medications signals possible cancer even if levels appear "normal" 4
Critical Clinical Pitfall
Do not delay referral or workup based on a single repeat PSA showing decrease - 43% of men with prostate cancer, including high-grade disease, show short-term PSA decreases below baseline, and this should not influence the decision to proceed with biopsy 5
Treatment Planning After Diagnosis
Once tissue diagnosis is obtained and staging is complete:
If localized disease (no metastases): Options include radical prostatectomy with extended lymph node dissection, external beam radiation therapy with androgen deprivation therapy, or enrollment in clinical trials 2
If metastatic disease is confirmed: Androgen deprivation therapy becomes primary treatment, with consideration of chemotherapy or novel systemic agents 2
Adjuvant androgen deprivation therapy should be considered for patients with positive lymph nodes found during surgery 2