What is the recommended treatment approach for a patient with a history of prostate cancer, previously on androgen deprivation therapy (ADT), now requiring definitive radiation therapy (RT) to the prostate, nodal volume, and an oligometastatic lesion in the ischium?

Treatment Approach for Oligometastatic Prostate Cancer with Nodal and Bone Involvement

This patient should receive definitive radiation therapy to the prostate, pelvic lymph nodes, and the oligometastatic ischial lesion, combined with continuation of ADT for a total duration of 24-36 months from initiation. 1

Comprehensive Treatment Strategy

Radiation Therapy Approach

Deliver definitive radiation to all sites of disease—prostate, involved pelvic nodes, and the ischial metastasis—as metastasis-directed therapy for oligometastatic disease is associated with prolonged biochemical progression-free survival and delays progression to castration-resistant disease. 2, 3

• The oligometastatic paradigm supports aggressive local therapy to all visible disease sites when ≤3-5 metastases are present 2, 4
• High-dose radiation (normalized total dose >64 Gy in 2 Gy equivalents) to metastatic lesions significantly improves biochemical relapse-free survival (65% vs 41.8% at 3 years, p=0.005) 4
• Stereotactic body radiotherapy (SBRT) to oligometastatic sites achieves 100% local control with minimal toxicity when delivered at 30-50 Gy in 3-5 fractions 2
• For the ischial lesion specifically, SBRT doses of 30 Gy in 3 fractions or 50 Gy in 10 fractions are appropriate 2

Androgen Deprivation Therapy Duration

Continue ADT for a total duration of 24-36 months from initiation, as this represents the standard for very high-risk and oligometastatic disease. 1, 5

• Long-term ADT (2-3 years) combined with definitive radiation is the NCCN-recommended standard for very high-risk disease (T3b-T4) and high-risk features 1
• RTOG 92-02 demonstrated superior outcomes with long-term (2+ years) versus short-term (4 months) ADT in high-risk patients, with particular benefit in Gleason 8-10 disease showing improved overall survival (45% vs 32%, p=0.0061) 1
• Calculate total ADT duration from initiation to determine when to discontinue, targeting 24-36 months total 1
• Continuous ADT is preferred over intermittent ADT for metastatic hormone-naïve prostate cancer 6

Radiation Dose and Technique Specifications

Deliver high-dose radiation using modern techniques to maximize tumor control while minimizing toxicity:

• Prostate and involved pelvic nodes: Use 3D conformal or intensity-modulated radiation therapy with doses appropriate for definitive treatment 5
• Oligometastatic ischial lesion: SBRT with 30 Gy in 3 fractions or 50 Gy in 10 fractions provides excellent local control 2
• Ensure normalized total dose exceeds 64 Gy (2 Gy equivalent) to metastatic sites, as this is the threshold associated with improved biochemical control 4

Surveillance and Monitoring Strategy

PSA and Clinical Monitoring

Measure PSA every 3 months for the first 5 years given the very high-risk classification, then every 6 months thereafter. 1

• More frequent PSA testing (every 3 months) is warranted for very high-risk disease 1
• Calculate PSA velocity and doubling time at each visit to assess for biochemical recurrence 1
• Perform digital rectal examination every 6-12 months to assess for local recurrence 1

Advanced Imaging for Recurrence Detection

If PSA rises (biochemical failure defined as nadir + 2 ng/mL), immediately initiate workup with PSMA PET/CT and multiparametric MRI. 1, 7

• PSMA PET combined with multiparametric MRI provides optimal detection of local intraprostatic recurrence 7, 1
• Radiographic staging via PSMA PET and mpMRI should be performed to exclude additional metastatic disease and identify the extent of any recurrence 7
• Biopsy confirmation is required before any salvage local therapy to avoid excessive toxicity in patients whose radiographic findings may represent treatment effect 7

ADT-Related Complication Monitoring

Assess for metabolic, cardiovascular, and bone health complications at each visit, as ADT side effects are cumulative over time. 1

• Monitor for hot flashes, weight gain, loss of libido, erectile dysfunction, osteoporosis, metabolic syndrome, and cardiovascular risk 1
• Consider bone density screening and calcium/vitamin D supplementation 1
• Monitor lipid profile, glucose, and cardiovascular risk factors 1
• Screen for depression, anxiety, and body image concerns 1

Expected Outcomes and Prognosis

This aggressive multimodal approach can achieve prolonged disease control with median ADT-free survival of 25 months after completion of initial ADT course and 3-year biochemical relapse-free survival rates of 54-66%. 2, 4

• Patients with hormone-sensitive oligometastatic prostate cancer treated with definitive RT achieve median biochemical progression-free survival of 17.2 months 3
• When peri-RT ADT is used with recovery of testosterone, 24-month biochemical progression-free survival reaches 77% 3
• Three-year overall survival rates exceed 92% with this combined approach 4
• Local control rates at metastatic sites approach 100% with SBRT 2

Critical Pitfalls to Avoid

Do not treat based on imaging alone—biopsy confirmation is mandatory before any salvage therapy to avoid treating treatment effect rather than true recurrence. 7

• PSMA PET has a recognized false-positive rate, and local salvage therapy should only be performed after pathologic confirmation 7
• Both systematic and targeted biopsies are necessary, as each detects approximately 6-8% of cancers missed by the other modality 1
• For local-only intraprostatic recurrence confirmed by imaging and biopsy, salvage options include SBRT, HDR brachytherapy, or LDR brachytherapy 1

Do not discontinue ADT prematurely—the full 24-36 month course is essential for optimal outcomes in oligometastatic disease. 1, 5