What is the best treatment approach for an elderly man with a history of high-risk prostate cancer, previously treated with prostatectomy and adjuvant radiation, now presenting with a Prostate-Specific Antigen (PSA) level of 0.3 and a 5 mm left iliac lymph node metastasis on Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) scan?

Treatment Approach for Oligometastatic Biochemical Recurrence After Prostatectomy

For this elderly patient with PSA 0.3 ng/mL and a single 5 mm PSMA-positive iliac lymph node after prostatectomy and adjuvant radiation, salvage radiotherapy to the prostatic bed and pelvic lymph nodes combined with short-term androgen deprivation therapy (ADT) represents the optimal treatment approach, provided life expectancy exceeds 10 years. 1

Initial Risk Stratification and Life Expectancy Assessment

• Life expectancy determines treatment intent: Patients with life expectancy >10 years should pursue curative salvage treatment, while those with <10 years should consider observation or palliative approaches only 1
• Elderly men (>70 years) have higher-grade disease and worse survival compared to younger counterparts, making age-appropriate treatment selection critical 1
• For men aged 75+ with PSA <3.0 ng/mL, they are unlikely to die from prostate cancer and may safely discontinue aggressive surveillance 1, 2

Confirmation of Biochemical Recurrence

• This patient meets standard criteria for biochemical recurrence: PSA ≥0.2 ng/mL with confirmatory level ≥0.2 ng/mL after radical prostatectomy 1
• The PSA of 0.3 ng/mL represents early biochemical failure, which is optimal timing for salvage intervention 1

PSMA PET/CT Findings and Prognostic Implications

• PSMA PET/CT is the most sensitive imaging modality for detecting occult metastatic disease at low PSA levels, with detection rates of 75% at PSA 0.01-0.2 ng/mL and 100% at PSA 0.2-4 ng/mL 3
• The single 5 mm left iliac lymph node represents oligometastatic disease, which is amenable to metastasis-directed therapy combined with systemic treatment 1
• PSMA PET findings are prognostic: higher lesion numbers predict less favorable outcomes to salvage therapy, but single-lesion disease has better prognosis 4

Salvage Radiotherapy: Timing and Target Volume

Salvage radiotherapy should be initiated immediately at this PSA level of 0.3 ng/mL for the following evidence-based reasons:

• 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 1
• Initiating salvage radiotherapy above PSA 0.25 ng/mL is associated with significantly increased all-cause mortality risk (HR 1.49,95% CI 1.11-2.00) compared to treatment at PSA ≤0.25 ng/mL 5
• The minimum radiation dose should be 64-66 Gy to the prostatic bed 1

Target Volume Considerations

• Pelvic lymph node irradiation is indicated given the PSMA-positive left iliac node, though the prostatic bed remains the primary target 6
• The defined target volumes include the prostate bed, with pelvic lymph nodes irradiated when nodal involvement is detected 6
• Extended pelvic lymph node dissection carries nearly 20% complication risk, making radiation-based treatment preferable to surgical nodal dissection 6

Androgen Deprivation Therapy Integration

Short-term ADT (4-6 months) should be combined with salvage radiotherapy based on the following evidence:

• ADT combined with radiotherapy shows significant improvements in biochemical recurrence, metastatic recurrence, metastasis-free survival, and overall survival across multiple trials 6
• For intermediate-risk disease (which this patient represents with single nodal metastasis), short duration of 4-6 months is optimal 6
• ADT should NOT be initiated for biochemical relapse alone without radiotherapy, as retrospective series show no survival benefit despite delayed time to clinical metastases 1
• If ADT is used, intermittent rather than continuous therapy should be employed, based on Level I evidence showing non-inferior overall survival with superior quality of life 1

ADT Considerations for Elderly Patients

• Patients receiving ADT are at risk for osteoporosis and should have baseline bone mineral density assessment 6
• Supplementation with calcium (500 mg) and vitamin D (400 IU) is recommended 6
• Men who are osteopenic or osteoporotic should be considered for bisphosphonate therapy 6

Alternative Treatment Options and Their Limitations

Observation Alone

• Not recommended for this patient if life expectancy >10 years, as observation is reserved for elderly men or frail patients with comorbidity that will likely out-compete prostate cancer 6
• Observation risks missing the curative window, as treatment of larger, more aggressive cancer may be more complex with greater side effects 6

Systemic ADT Alone

• ADT alone without radiotherapy provides no survival benefit for biochemical recurrence 1
• Should only be considered for proven distant metastatic disease or when salvage radiotherapy is not feasible 6

Metastasis-Directed Therapy to Lymph Node Only

• Treating only the visible lymph node without prostatic bed radiation ignores potential microscopic disease in the surgical bed 6
• The prostatic bed remains the primary site of recurrence after prostatectomy with positive surgical margins or extracapsular extension 6

Monitoring After Salvage Treatment

• PSA should be monitored every 3-6 months initially after salvage radiotherapy, then annually indefinitely 1
• PSA doubling time <6 months is associated with higher risk and need for further intervention 1
• PSMA PET response shows moderate-to-high concordance with PSA response (Cohen's κ = 0.623) when monitoring treatment response 3

Critical Pitfalls to Avoid

• Do not delay salvage radiotherapy to wait for higher PSA levels to improve PSMA PET detection rates, as this significantly worsens survival outcomes 5
• Do not initiate ADT alone without concurrent radiotherapy for oligometastatic disease, as this represents a missed curative opportunity 1
• Do not omit pelvic nodal irradiation when PSMA PET demonstrates nodal involvement 6
• Do not pursue aggressive treatment if life expectancy is <10 years, as harms substantially outweigh benefits 1, 7

Special Considerations for High-Risk Features

This patient has already received adjuvant radiation, which complicates the salvage approach:

• Previous pelvic radiation limits re-irradiation options and increases toxicity risk 6
• Consider referral to radiation oncology for assessment of feasibility and dose constraints given prior radiation exposure
• If re-irradiation is not feasible, systemic ADT with consideration of novel androgen receptor pathway inhibitors (enzalutamide) may be appropriate 8