What is the optimal treatment approach for a 79-year-old male with high-volume metastatic prostate cancer and PSMA expression, who has a history of prostate cancer recurrence and a current PSA level of 0.2?

From the Guidelines

For a 79-year-old male with high-volume metastatic prostate cancer showing PSMA expression, recurrent disease, and a PSA of 0.2, the optimal treatment approach would be 177Lu-PSMA-617 therapy, considering the patient's cancer expresses PSMA and has received prior ADT and docetaxel is not mentioned but is a consideration for treatment intensification. Given the patient's history of prostate cancer recurrence and current PSA level of 0.2, it is crucial to consider the most recent and highest quality evidence-based treatment options. According to the updated treatment recommendations for prostate cancer from the ESMO clinical practice guideline 1, 177Lu-PSMA-617 is recommended for men with cancer expressing PSMA on positron emission tomography-PSMA and without PSMA non-expressing lesions, which aligns with this patient's profile.

Some key points to consider in the management of this patient include:

• The use of ADT alone is not recommended for fit men with metastatic hormone-sensitive prostate cancer, unless they cannot tolerate treatment intensification 1.
• The combination of ADT with novel hormone agents (such as abiraterone, apalutamide, darolutamide, or enzalutamide) or docetaxel is recommended for first-line treatment of metastatic hormone-sensitive prostate cancer 1.
• Bone-targeted therapy with zoledronic acid or denosumab should be considered if bone metastases are present.
• Regular monitoring of PSA levels, imaging, and potential side effects is essential for optimal management.

In terms of specific treatment regimens, the patient should receive 177Lu-PSMA-617 therapy, and consideration should be given to combining this with ADT and/or other novel hormone agents, depending on the patient's overall health and tolerance to treatment. The patient's age and comorbidities should be carefully considered when determining the intensity of treatment.

Overall, the goal of treatment should be to improve the patient's quality of life, while also extending life expectancy and reducing the risk of morbidity and mortality associated with metastatic prostate cancer.

From the FDA Drug Label

The major efficacy outcome measure was radiographic progression-free survival (rPFS) based on blinded independent central review (BICR) Radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. XTANDI demonstrated a statistically significant improvement in rPFS and OS compared to placebo. Consistent rPFS results were observed in patients with high or low volume of disease and patients with and without prior docetaxel therapy Table 14. Efficacy Results in ARCHES (Intent-to-Treat Analysis) XTANDI (N = 574) Radiographic Progression-free Survival* Number of events (%) 89 (15.5) Radiographic disease progression 77 (13.4) Death within 24 weeks after treatment discontinuation 12 (2.1) Median, months (95% CI)† NR Hazard ratio (95% CI)‡ 0.39 (0.30,0.50) P-value§ p < 0.0001

The optimal treatment approach for a 79-year-old male with high-volume metastatic prostate cancer and PSMA expression, who has a history of prostate cancer recurrence and a current PSA level of 0.2, is not explicitly stated in the provided drug labels. However, based on the information provided, enzalutamide (XTANDI) has demonstrated a statistically significant improvement in radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo in patients with high-volume metastatic prostate cancer.

• Key points:
  • XTANDI has shown significant improvement in rPFS and OS.
  • The treatment is suitable for patients with high-volume metastatic prostate cancer.
  • The patient's current PSA level and history of recurrence are relevant factors in determining the treatment approach.
• Considerations:
  • The patient's age and overall health should be taken into account when considering treatment options.
  • The potential benefits and risks of XTANDI, including adverse reactions and interactions, should be carefully evaluated.
• Recommendation:
  • Based on the available data, XTANDI may be a suitable treatment option for this patient, but the decision should be made in consultation with a healthcare professional, considering the patient's individual circumstances and medical history 2.

From the Research

Treatment Approach for Metastatic Prostate Cancer

• The patient's condition, with high-volume metastatic prostate cancer and PSMA expression, suggests that Lutetium-177 PSMA therapy could be a viable treatment option 3, 4.
• Studies have shown that Lutetium-177 PSMA therapy can prolong imaging-based progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer 4.
• The patient's history of prostate cancer recurrence and current PSA level of 0.2 may indicate a need for aggressive treatment, and Lutetium-177 PSMA therapy has been shown to be effective in similar cases 5, 6.

Considerations for Treatment

• The patient's age (79 years) and overall health should be taken into account when considering treatment options, as Lutetium-177 PSMA therapy can have side effects and may not be suitable for all patients 4, 6.
• The expression of PSMA in the patient's cancer is a key factor in determining the effectiveness of Lutetium-177 PSMA therapy, and studies have shown that high PSMA expression is associated with better outcomes 7.
• The patient's history of initial surgery, radiation, and 18 months of ADT, as well as the recurrence of cancer 3 years later, suggests that a combination of treatments may be necessary to achieve optimal results 6.

Potential Treatment Outcomes

• Studies have shown that Lutetium-177 PSMA therapy can lead to significant improvements in progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer 4, 6.
• The patient's PSA level of 0.2 may indicate a good response to treatment, and studies have shown that Lutetium-177 PSMA therapy can lead to significant reductions in PSA levels 5, 6.
• However, the patient's age and overall health, as well as the presence of metastatic disease, may affect treatment outcomes, and close monitoring and adjustment of treatment plans may be necessary 4, 6.