Management of Biochemical Recurrence After Radical Prostatectomy and Salvage Radiation

Understanding the Clinical Context

A patient with a detectable PSA level after prior radical prostatectomy and salvage radiation therapy meets criteria for biochemical recurrence, requiring immediate referral to a specialist for consideration of systemic therapy, such as androgen deprivation therapy (ADT) or newer agents like enzalutamide, according to the European Society for Medical Oncology 1, 2
The PSA doubling time (PSADT) is a key prognostic factor, with a PSADT of less than 3 months indicating aggressive disease that requires immediate systemic therapy, as recommended by the European Association of Urology 1

To confirm biochemical recurrence, PSA should be repeated in 4-8 weeks to calculate PSADT, and a rising PSA on two consecutive measurements confirms biochemical recurrence, as suggested by the National Comprehensive Cancer Network 2
PSMA-PET/CT is the preferred imaging modality for restaging evaluation at a PSA level below 10 ng/mL, as it can detect occult metastatic disease at PSA levels as low as 0.2 ng/mL, according to the American Urological Association 2, 3
Testosterone level should be measured to confirm castration-sensitive disease, with a level of ≥150 ng/dL, as recommended by the European Society for Medical Oncology 3

Continuous ADT with GnRH analog or bilateral orchiectomy is a first-line hormonal therapy option, as recommended by the American Society of Clinical Oncology 1
Regular exercise can reduce fatigue and improve quality of life during ADT, and monitoring for cardiovascular effects, osteoporosis, and metabolic syndrome is essential, as suggested by the European Association of Urology 1
Intermittent ADT is an option for biochemical relapse after radiation to reduce cumulative side effects, according to the National Comprehensive Cancer Network 1

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, as recommended by the International Society of Geriatric Oncology 1, 4
However, if PSADT is rapid (<3 months) or the patient develops symptoms, treatment should not be delayed regardless of age, according to the American Geriatrics Society 1

If systemic therapy is initiated, PSA monitoring every 3 months initially, and testosterone levels to confirm castration (<50 ng/dL) if on ADT, are essential, as recommended by the European Society for Medical Oncology 6, 3
Bone density screening and cardiovascular risk assessment should be performed given ADT side effects, as suggested by the National Osteoporosis Foundation and the American Heart Association 1