Optimal Long-Term Management for Node-Positive PSA Recurrence After Prostatectomy with Complete Response to ADT Plus Abiraterone
Direct Recommendation
Continue indefinite ADT (leuprolide) with abiraterone plus prednisone until disease progression, given the complete nodal response and high-risk features (Gleason 8, N1 disease). 1
Rationale and Treatment Algorithm
Primary Treatment Strategy: Continuation of Combination Therapy
The STAMPEDE trial demonstrated that ADT plus abiraterone and prednisolone in node-positive (N1) nonmetastatic disease achieved a 79% relative improvement in failure-free survival (HR: 0.21,95% CI 0.15-0.31) compared to ADT alone. 1
For patients with N1 disease who achieve response, treatment should continue until progression rather than stopping at an arbitrary timepoint. 1
The LATITUDE trial in high-risk metastatic disease showed median overall survival of 53.3 months with abiraterone plus prednisone versus 36.5 months with ADT alone (HR 0.66, p<0.0001), establishing the mortality benefit of continuing combination therapy. 2
Duration of Therapy Considerations
In the STAMPEDE trial, for patients with N1 nonmetastatic disease, treatment with abiraterone plus prednisolone continued until progression (not limited to 2 years as in M0 disease without planned radiotherapy). 1
The median treatment duration in STAMPEDE was 23.9 weeks (14.9-46.4), but this reflects the entire cohort; patients with ongoing response continued beyond this median. 1
For node-positive disease after radical prostatectomy, early adjuvant ADT achieved 10-year cancer-specific survival of 80%, supporting indefinite continuation in responding patients. 1
Monitoring Strategy During Continued Treatment
PSA should be monitored every 3-6 months to detect biochemical progression early. 1
PSMA PET/CT is the most sensitive imaging modality for detecting progression and should be performed if PSA rises or at regular intervals (every 6-12 months) to assess ongoing complete response. 1, 3
Monitor for mineralocorticoid excess adverse events (hypertension, hypokalemia, edema) which occurred in 21% (hypertension) and 12% (hypokalemia) of patients receiving abiraterone in LATITUDE. 2
Liver function tests should be monitored regularly given 7% incidence of grade 3-5 liver toxicity with abiraterone. 1
Alternative Considerations if Progression Occurs
If PSA progression occurs while on abiraterone plus ADT, consider switching to enzalutamide plus ADT, which showed metastasis-free survival benefit in the EMBARK trial (HR 0.42 for enzalutamide plus leuprolide vs placebo plus leuprolide). 4
Salvage radiotherapy to the pelvis should be considered if oligoprogression is detected on PSMA PET, as pelvic RT combined with long-term ADT showed local control improvement in pN+ disease. 1
Docetaxel chemotherapy can be added to ADT in castration-sensitive disease if widespread progression occurs, based on evidence from metastatic castration-naive prostate cancer trials. 1
Critical Pitfalls to Avoid
Do not discontinue abiraterone arbitrarily at 2 years in this N1 patient—the 2-year duration in STAMPEDE applied only to M0 patients receiving radiotherapy, not to N1 patients or those with progression risk. 1, 5
Do not use intermittent ADT in this high-risk setting (Gleason 8, N1 disease)—the INT-0162/SWOG-9346 trial demonstrated that intermittent ADT is inferior to continuous ADT for overall survival in metastatic disease. 6
Maintain castrate testosterone levels (<50 ng/dL) continuously; verify castrate levels every 3-6 months as some patients on LHRH agonists fail to achieve adequate suppression with standard dosing intervals. 7
Do not add enzalutamide to ongoing abiraterone—the STAMPEDE meta-analysis showed no additional benefit from concurrent enzalutamide with abiraterone (interaction HR 1.02, p=0.91). 5
Quality of Life and Toxicity Management
The most common grade 3-4 adverse events with abiraterone are hypertension (21%) and hypokalemia (12%), which are manageable with antihypertensives and potassium supplementation. 2
Patient-reported outcomes in LATITUDE showed improvements in pain intensity, fatigue, and overall health-related quality of life with abiraterone despite treatment-related toxicities. 1
Consider breast irradiation (8-15 Gy in 1-3 fractions) 1-2 weeks before continuing LHRH agonist therapy to prevent painful gynecomastia. 1
Summary Treatment Plan
Continue leuprolide (LHRH agonist) indefinitely with abiraterone 1000 mg daily plus prednisone 5 mg daily until disease progression, monitoring PSA every 3-6 months, PSMA PET every 6-12 months, blood pressure and electrolytes monthly initially then every 3 months, and liver function tests every 2 weeks for 3 months then monthly. 1, 2 This approach maximizes overall survival and failure-free survival based on the highest-quality evidence from STAMPEDE and LATITUDE trials in node-positive disease. 1, 2