Management of Biochemical Recurrence in Prostate Cancer

Clinical Situation Assessment

A patient with a history of prostate cancer treated with radiation therapy and prior hormonal treatments, such as leuprolide, may be at risk for biochemical recurrence, as indicated by rising PSA levels and positive PSMA PET findings 1
The presence of ill-defined nodular density with moderate radiotracer uptake in the anterior and inferior aspect of the right hemipelvis on PSMA PET is consistent with recurrent disease 2
A CT CAP showing no evidence of metastatic disease, stable prostatomegaly, and stable Crohn's disease is important in assessing the extent of disease 1

The National Comprehensive Cancer Network (NCCN) guidelines suggest that a rising PSA pattern with positive PSMA PET findings but negative conventional imaging indicates biochemical recurrence progressing to early castration-resistant prostate cancer (CRPC) 1, 3
The patient has non-metastatic CRPC by conventional imaging but with PSMA-avid disease, as defined by the presence of positive PSMA PET findings 4

The NCCN recommends initiating a novel hormonal agent, such as enzalutamide, as the next line of therapy for patients with biochemical recurrence and positive PSMA PET findings 1
Enzalutamide is FDA-approved for castration-resistant prostate cancer and has shown efficacy in delaying metastasis in patients with rising PSA 1

The European Society for Medical Oncology (ESMO) recommends PSA measurements every 3-4 weeks initially to assess response to enzalutamide 5
Regular imaging follow-up with CT scans every 2-4 months, bone scintigraphy every 2-4 months, and consideration of repeat PSMA PET in 3-6 months to assess response are recommended 5, 4

Apalutamide could be considered as an alternative novel hormonal agent for patients who cannot tolerate enzalutamide, with similar efficacy in non-metastatic CRPC 3
Darolutamide is another option with potentially fewer central nervous system side effects 3

If disease progresses on enzalutamide, consideration of docetaxel chemotherapy, 177Lu-PSMA-617 therapy, or cabazitaxel as later-line options is recommended 1, 3, 4, 2

The American Urological Association (AUA) recommends monitoring for potential adverse effects of enzalutamide, including seizures, fatigue, hypertension, and hot flashes 1
Continuing androgen deprivation therapy (ADT) concurrently with enzalutamide is recommended 1
The patient's Crohn's disease should be monitored during treatment as it may affect medication tolerance 1

The NCCN recommends avoiding reliance solely on PSA for monitoring response, as radiographic progression can occur without PSA elevation in up to 24.5% of patients on novel hormonal agents 4
Discontinuing therapy based on PSA progression alone should be avoided, and treatment should be continued until clinical progression or intolerability 1
Consideration of the patient's prior adverse effects with abiraterone is important when selecting the next agent and monitoring for side effects 1
Delaying treatment initiation should be avoided, as early intervention with novel hormonal agents has shown improved outcomes in delaying metastasis and improving survival 3