What is the likely overall survival for a 79-year-old patient with high-volume metastatic castration-resistant prostate cancer, currently on Docetaxel (Docetaxel), Apalutamide (Apalutamide), and Androgen Deprivation Therapy (ADT), with Prostate-Specific Membrane Antigen (PSMA) expression, minimal Prostate-Specific Antigen (PSA) production, and planned treatment with Lutetium-177 (LU-177)?

Overall Survival for High-Volume Metastatic Castration-Resistant Prostate Cancer

The likely overall survival for this 79-year-old patient with high-volume metastatic castration-resistant prostate cancer is approximately 15-18 months based on the VISION trial data for patients who will receive Lu-177-PSMA-617 after docetaxel progression. 1

Current Treatment Profile and Prognostic Factors

The patient's current treatment regimen and clinical characteristics include:

• High-volume metastatic castration-resistant prostate cancer (mCRPC)
• Current treatment with Docetaxel, Apalutamide, and ADT
• PSMA expression (positive prognostic factor for Lu-177 response)
• Low PSA production (potentially indicating aggressive phenotype)
• Good overall health status at age 79 (positive prognostic factor)
• Planned Lu-177-PSMA-617 therapy upon progression

Survival Estimates Based on Evidence

Lu-177-PSMA-617 Therapy Outcomes

• The VISION trial demonstrated that Lu-177-PSMA-617 plus standard of care significantly improved overall survival to 15.3 months compared to 11.3 months with standard of care alone (4.0-month absolute survival gain) in patients previously treated with androgen receptor pathway inhibition and taxane-based chemotherapy 1, 2
• The hazard ratio for death was 0.62 (95% CI 0.52-0.74; p<0.001), indicating a 38% reduction in the risk of death with Lu-177-PSMA-617 2

Factors That May Influence Survival

1. PSMA Expression: The patient's positive PSMA expression is favorable for response to Lu-177 therapy 1

2. Low PSA Production: This may indicate a more aggressive phenotype, potentially negatively impacting survival 1

3. Good Health Status: The patient's good overall health status at age 79 is a positive prognostic factor that may improve treatment tolerance and potentially extend survival beyond median estimates 1

4. Current Treatment Response: Current response to Docetaxel, Apalutamide, and ADT will influence the timing of progression and subsequent Lu-177 therapy initiation

Comparative Data from Recent Trials

• The TheraP trial showed similar overall survival between Lu-177-PSMA-617 and cabazitaxel (19.1 months vs 19.6 months) in patients with mCRPC progressing after docetaxel 3

• In chemotherapy-naïve patients, a phase 2 trial showed comparable overall survival between Lu-177-PSMA-617 and docetaxel (19.0 months vs 15.0 months) 4

• The ENZA-p trial demonstrated improved overall survival with the combination of Lu-177-PSMA-617 plus enzalutamide compared to enzalutamide alone (34 months vs 26 months; HR 0.55) 5

Potential Complications to Consider

• Grade 3-4 adverse events are more common with Lu-177-PSMA-617 compared to standard of care (52.7% vs 38%) 1, 2

• Therapy-related myeloid neoplasms have been reported in approximately 1.3% of patients receiving Lu-177-PSMA therapy, particularly in those with extensive prior treatments 6

Conclusion for This Patient

Given the patient's good health status, PSMA expression, and planned sequential therapy with Lu-177-PSMA-617 after docetaxel progression, his overall survival is likely to be in the range of 15-18 months from the time of Lu-177-PSMA-617 initiation, potentially extending longer due to his good performance status. The timing of progression on current therapy will be a critical factor in determining when Lu-177-PSMA-617 therapy can be initiated.