Treatment Approach for Advanced Prostate Cancer with Pelvic Nodal Metastasis After Partial Response to Triptorelin and Radiation
Continue triptorelin (or another GnRH agonist) indefinitely to maintain castrate testosterone levels, and add either abiraterone with prednisolone or docetaxel chemotherapy as intensification therapy for metastatic hormone-sensitive disease. 1
Maintain Continuous Androgen Deprivation Therapy
ADT must be continued indefinitely, even after progression or when adding additional therapies. 1 The patient has pelvic nodal metastasis, which classifies this as metastatic disease requiring lifelong testosterone suppression to castrate levels (<50 ng/dL). 1, 2
Triptorelin should be maintained at the current dosing schedule (3.75 mg every 4 weeks, 11.25 mg every 12 weeks, or 22.5 mg every 24 weeks). 2, 3, 4 If the patient experienced only a "partial response," verify that castrate testosterone levels (<50 ng/dL, ideally <20 ng/dL) are being achieved and maintained. 1, 5
Common pitfall: Discontinuing ADT when adding novel hormonal agents or chemotherapy—this significantly worsens outcomes. 1, 6 Castration must be maintained throughout all subsequent lines of therapy.
Add Intensification Therapy for Metastatic Hormone-Sensitive Disease
Since the patient has metastatic disease (pelvic nodal involvement) and has already received radiation therapy with ADT, the next step is intensification:
First-Line Intensification Options:
Option 1: Abiraterone acetate plus prednisolone 1
- The STAMPEDE trial demonstrated that adding abiraterone 1000 mg daily plus prednisolone 5 mg daily to ADT significantly improved failure-free survival (HR 0.21,95% CI 0.15-0.31) in patients with nonmetastatic node-positive disease. 1
- This combination showed a 79% relative improvement in progression outcomes for patients with pelvic nodal disease. 1
- Abiraterone is a category 1 recommendation for metastatic castration-sensitive prostate cancer when combined with ADT. 1
Option 2: Docetaxel chemotherapy 1, 7
- For patients fit enough for chemotherapy, adding docetaxel to ADT at initial diagnosis of metastatic disease provides survival benefit. 1, 7
- This represents a paradigm shift from sequential therapy and is appropriate for metastatic hormone-sensitive disease. 7
- Docetaxel is typically given as 75 mg/m² every 3 weeks for 6 cycles. 1
Decision Algorithm:
If the patient has good performance status, no significant comorbidities, and can tolerate chemotherapy: Consider docetaxel as it provides the strongest survival data in metastatic hormone-sensitive disease. 1, 7
If the patient has significant comorbidities, poor performance status, or prefers to avoid chemotherapy: Choose abiraterone plus prednisolone, which is oral and generally better tolerated. 1
If the patient has visceral metastases or high-volume disease: Docetaxel is preferred as it has demonstrated benefit in this population. 1
Monitor for Castration-Resistant Progression
Continue monitoring PSA every 3 months and testosterone levels to confirm castrate levels are maintained. 1, 7
Castration-resistant prostate cancer (CRPC) is defined as: Clinical, radiographic, or biochemical progression despite castrate testosterone levels (<50 ng/dL). 1
If progression occurs on ADT plus intensification therapy, the patient has developed metastatic CRPC and requires second-line systemic therapy (enzalutamide, abiraterone if not already used, cabazitaxel, or radium-223 if bone metastases are present). 1
Critical Warnings and Monitoring
Cardiovascular risk: ADT increases risk of myocardial infarction, sudden cardiac death, and stroke. 8, 2 Monitor cardiovascular disease according to institutional guidelines and manage risk factors aggressively. 1, 2
Metabolic syndrome: GnRH agonists increase risk of hyperglycemia, diabetes, hyperlipidemia, and non-alcoholic fatty liver disease. 2 Monitor lipids, blood glucose, and HbA1c regularly. 2
Bone health: Patients on long-term ADT require monitoring for osteoporosis and should receive bone-modifying agents (denosumab or zoledronic acid) if bone metastases develop. 1
QT prolongation: ADT may prolong the QT interval; consider baseline and periodic ECG monitoring, especially when combining with other QT-prolonging medications. 2
Avoid Common Errors
Do not stop ADT when adding abiraterone or chemotherapy—this is the most critical error and significantly worsens outcomes. 1, 6
Do not delay intensification therapy in patients with metastatic disease who have already received radiation and ADT—early addition of systemic therapy improves survival. 1, 7
Do not use intermittent ADT in patients with metastatic disease—continuous ADT is required. 1, 7
Do not repeat triptorelin if the patient has progressed on it unless switching to a different mechanism (novel hormonal therapy or chemotherapy). 1 However, ADT itself must continue to maintain castration.