What is the next step for an elderly patient with a history of radical prostatectomy (surgical removal of the prostate) for prostate cancer (prostate Ca) with an abnormal Prostate-Specific Antigen (PSA) level?

Management of Detectable PSA After Radical Prostatectomy

The immediate next step is to repeat the PSA measurement in 4-8 weeks to confirm the finding and calculate PSA doubling time, then refer to the treating specialist for consideration of salvage radiotherapy, which should be initiated at the earliest sign of recurrence and at the lowest possible PSA level (ideally <0.5 ng/mL) to maximize disease control. 1, 2

Confirm Biochemical Recurrence

• Repeat PSA testing at 8 weeks post-surgery to determine if the level is still declining toward undetectable or if it meets criteria for biochemical persistence 1
• Biochemical recurrence is defined as a confirmed PSA ≥0.2 ng/mL with a second confirmatory level ≥0.2 ng/mL 3, 2
• Use the same laboratory assay for longitudinal monitoring, as laboratory variability can range from 20-25% between different assays 1
• PSA should drop to undetectable levels (less than 0.03 ng/mL) within 2 months after radical prostatectomy 1

Calculate PSA Kinetics

• PSA doubling time (PSADT) is the critical prognostic factor that determines urgency and treatment approach 2, 4
• PSADT <3 months indicates aggressive disease requiring immediate systemic therapy 2, 4
• PSADT <6-10 months predicts worse outcomes with salvage therapy and warrants earlier intervention 2
• PSADT >15 months with PSA <1.0 and Gleason score <7 may allow for closer observation 3, 2

Restaging Evaluation

• PSMA PET/CT is the preferred imaging modality for detecting occult metastatic disease at PSA levels below 10 ng/mL 2, 4
• Conventional imaging (bone scan, CT) has extremely low yield when PSA is below 10 ng/mL and should not be relied upon 3, 2
• Pelvic imaging should be obtained unless the disease is low-volume and low-risk (PSA <1.0, Gleason score <7, PSA doubling time >15 months) 3, 2
• Consider restaging evaluation to determine if recurrence is local versus metastatic, as this guides salvage strategy selection 3, 2

Treatment Decision Algorithm

If No Distant Metastases on Imaging:

• Offer salvage radiotherapy immediately - this is the only potentially curative treatment for biochemical failure after prostatectomy 3, 2, 5
• Salvage radiotherapy should be delivered at minimum dose of 64-66 Gy to the prostatic bed 2
• Outcomes are dramatically better when PSA is lower at treatment initiation: patients receiving radiotherapy at PSA <0.5 ng/mL achieve 6-year biochemical progression-free survival of 48%, compared to only 18% when PSA is >1.5 ng/mL 2
• Salvage radiotherapy reduces biochemical recurrence, local recurrence, and clinical progression 3
• Early salvage radiotherapy can reduce mortality, with greatest benefit in patients with PSA doubling time <6 months 3, 2

If Distant Metastases Detected:

• Refer for systemic therapy with androgen deprivation therapy (ADT) or newer agents like enzalutamide 4
• Measure testosterone level to confirm castration-sensitive disease (≥150 ng/dL) 4
• Continuous ADT with GnRH analog or bilateral orchiectomy is first-line hormonal therapy 4

Special Considerations for Elderly Patients

• In elderly patients with limited life expectancy (<10 years) and slow PSADT (>10 months), watchful waiting with delayed hormone therapy may be appropriate to avoid treatment-related morbidity 4
• However, if PSADT is rapid (<3 months) or the patient develops symptoms, treatment should not be delayed regardless of age 4
• Consider comorbidities and functional status when weighing the risks and benefits of salvage radiotherapy 3

Adverse Prognostic Factors

• Gleason score 8-10 predicts poor response to salvage therapy 2
• Pre-salvage PSA >2 ng/mL is associated with worse outcomes 2
• Negative surgical margins paradoxically predict worse outcomes (suggesting distant disease) 2
• Seminal vesicle invasion indicates higher risk of systemic disease 2

Critical Pitfalls to Avoid

• Do not delay salvage radiotherapy while "watching" the PSA rise - every increment in PSA reduces the effectiveness of salvage treatment 2
• Do not rely on conventional imaging (bone scan, CT) at low PSA levels - these will miss occult disease 3, 2
• Do not initiate ADT reflexively without first considering salvage radiotherapy, as radiotherapy is the only potentially curative option 2, 5
• Do not use different laboratory assays for serial PSA measurements due to 20-25% inter-assay variability 1

Follow-up Protocol

• If PSA becomes undetectable after salvage radiotherapy: continue PSA monitoring every 6-12 months for the first 5 years, then annually thereafter 1
• If PSA remains detectable or rises after salvage radiotherapy: consider systemic therapy with ADT 4
• Monitor for salvage radiotherapy adverse effects including urinary, bowel, and sexual dysfunction 3