What is the best course of action for an elderly man with a history of prostate cancer, treated with prostatectomy and adjuvant radiation, now presenting with rising Prostate-Specific Antigen (PSA) levels?

Biochemical Recurrence After Prostatectomy and Adjuvant Radiation: Salvage Radiotherapy is Indicated

This patient meets criteria for biochemical recurrence (PSA ≥0.2 ng/mL with confirmatory level ≥0.2 ng/mL) and should be offered salvage radiotherapy to the prostatic bed, ideally initiated now at PSA 0.3 ng/mL to maximize disease control. 1

Defining Biochemical Recurrence

• Biochemical recurrence is confirmed when PSA reaches ≥0.2 ng/mL with a second confirmatory level ≥0.2 ng/mL after radical prostatectomy. 2, 1
• This patient's rising PSA from <0.1 to 0.1 to 0.3 ng/mL clearly meets this threshold and represents treatment failure. 1

Immediate Action: Salvage Radiotherapy

Salvage radiotherapy should be offered as the primary treatment for PSA biochemical recurrence after prostatectomy without distant metastases, with treatment ideally initiated at the earliest sign of PSA recurrence and at the lowest possible PSA level (preferably <0.5 ng/mL). 1

Evidence Supporting Early Intervention

• 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, 1
• Approximately 50% of patients treated with salvage radiotherapy for isolated PSA elevation after prostatectomy remain free of biochemical relapse at 5 years. 3
• Achieving undetectable PSA after salvage radiotherapy is an independent predictor of favorable outcome, with evidence suggesting salvage radiotherapy may reduce prostate cancer-specific mortality. 1

Radiation Dose and Target

• A minimum dose of 64-66 Gy should be delivered to the prostatic bed. 1
• The defined target volumes include the prostate bed; pelvic lymph nodes may be irradiated but pelvic radiation is not necessary in most cases. 2

Pre-Treatment Restaging Evaluation

Re-staging evaluation should be considered to determine if recurrence is local versus metastatic, as this guides salvage strategy selection. 2, 1

Imaging Recommendations

• Pelvic imaging should be obtained unless the disease is low-volume and low-risk (PSA <1.0, Gleason score <7, and PSA doubling time >15 months). 1
• Imaging yield is extremely low when PSA is <10 ng/mL, particularly for bone scans. 1, 4
• PSMA PET/CT is the most sensitive imaging modality to detect metastases in patients with biochemical recurrence if available. 1
• Conventional bone scan is not justified at this PSA level and should not be ordered. 1, 5

Androgen Deprivation Therapy: NOT Recommended at This Time

Routine early androgen deprivation therapy (ADT) is NOT recommended for men with biochemical relapse unless they have symptomatic local disease progression, proven metastases, or PSA doubling time <3 months. 1

Evidence Against Early ADT

• Retrospective series evaluating ADT for relapse following radical prostatectomy observed no survival benefit, although time to clinical metastases was delayed by early androgen treatment. 1
• The PR.7 trial (1386 patients) comparing intermittent versus continuous ADT in biochemical relapse showed median overall survival of 8.8 versus 9.1 years respectively (HR 1.02; 95% CI 0.86-1.21), demonstrating no survival advantage for ADT initiation. 1
• Most patients with biochemical failure will have a good 15-year prognosis, with outcomes best approximated by absolute PSA level, PSA doubling time, and initial disease characteristics. 1

When to Consider ADT

ADT should only be considered if the patient develops: 1

• PSA doubling time <3 months
• Symptomatic local disease progression
• Proven metastatic disease on imaging

Prognostic Factors to Assess

Key factors predicting poor response to salvage therapy include Gleason score 8-10, pre-salvage PSA >2 ng/mL, negative surgical margins, PSA doubling time <10 months, and seminal vesicle invasion. 1, 3

• Calculate PSA doubling time from the available PSA values to better stratify risk. 1
• Patients without adverse features achieve 6-year progression-free survival of 69% with salvage radiotherapy. 1
• Review original pathology for Gleason score, surgical margin status, extracapsular extension, and seminal vesicle invasion. 2

Ongoing Monitoring Strategy

• PSA should be measured every 3-6 months during and after salvage radiotherapy to assess treatment response. 2
• Digital rectal examination annually is appropriate to monitor for local recurrence, though may be omitted if PSA remains undetectable. 2

Critical Pitfalls to Avoid

• Do not delay salvage radiotherapy waiting for PSA to rise further—efficacy decreases dramatically at higher PSA levels. 1
• Do not initiate ADT reflexively based solely on rising PSA when salvage radiotherapy is the appropriate treatment. 1
• Do not order bone scans or extensive metastatic workup at this low PSA level—the yield is negligible. 1, 5
• Do not counsel the patient that "nothing can be done"—salvage radiotherapy offers meaningful disease control in approximately 50% of patients. 3

Expected Treatment-Related Adverse Effects

Patients should be informed of possible short- and long-term urinary, bowel, and sexual adverse effects of radiotherapy, though these are generally modest and self-limited. 2, 3