Moderator: Dr. Peter Hammerer, Germany

Panellists: Dr. Priyamvada Maitre, India & Dr. Robert Reiter, United States

Important Takeaways

1. PSMA PET’s role in patient selection: PSMA PET/CT imaging is crucial for staging and guiding treatment, particularly in determining candidacy for Lutetium-177 PSMA therapy in cases of metastatic or oligometastatic prostate cancer.

2. Importance of genetic testing: For patients with castration-resistant prostate cancer (CRPC), testing for mutations such as BRCA2 and HRR mutations is key, as it guides potential treatments with PARP inhibitors.

3. Treatment sequencing challenges: High-volume disease or progression in CRPC presents complex treatment sequencing decisions, often requiring chemotherapy, followed by PSMA-targeted therapy if other options are exhausted.

4. Impact of radio theranostic factors: The success of Lutetium-177 therapy often depends on high PSMA uptake; additional imaging with FDG PET is recommended to confirm PSMA-positive, FDG-negative status for optimal outcomes.

5. Evolving criteria and future applications: Current trials are evaluating PSMA-targeted therapies in hormone-sensitive and high-risk settings, with the potential to expand usage earlier in the disease course.

Key Highlights

Dr. Hammerer highlighted that while radiopharmaceutical therapy is now an established option, several questions remain unanswered. Key challenges include identifying optimal patient selection through imaging, the best biomarkers like PSA, and appropriate dosing strategies. There is also ongoing research on its use in earlier stages, combination with other therapies, retreatment potential, and the role of alpha-particle isotopes. He expressed hope that future studies will address these gaps to improve patient outcomes.

Dr. Hammerer then initiated the case based panel discussions:

Case 1: High-Risk Biochemical Recurrence and Treatment Options 

A 62-year-old man with high-grade prostate cancer underwent radical prostatectomy and presented with biochemical recurrence (PSA 8.2 ng/mL). Conventional imaging was negative, so a PSMA PET scan was performed, which detected a PSMA-positive mass in the mediastinum, missed on earlier CT scans.

The panellists, led by Dr. Robert Reiter, discussed the patient's next steps, initially recommending genetic testing for BRCA2 and other mutations to determine the suitability for PARP inhibitors; however, the patient tested negative. Following this, docetaxel chemotherapy was initiated but halted after two cycles due to neutropenic sepsis and hematotoxicity. Given the patient’s poor chemotherapy tolerance, the panel debated between cabazitaxel and lutetium PSMA therapy, ultimately favouring the latter based on positive PSMA PET results. The patient completed six cycles of lutetium PSMA, resulting in a significant reduction in metastatic lesions. Dr. Maitre highlighted the importance of using PSMA PET with high uptake and negative FDG PET scans to identify optimal candidates for this therapy.

Case 2: Progression to mCRPC and Genetic Testing

The second case involved a patient initially misdiagnosed with lung cancer after an FDG PET scan showed extensive liver and bone lesions. Upon further evaluation, a PSA test revealed a level of 20,800, and a biopsy confirmed metastatic prostate cancer. The patient, diagnosed with metastatic hormone-sensitive prostate cancer, was treated with chemotherapy, darolutamide, and ADT, achieving initial remission, including complete resolution of liver metastases. 

During the panel discussion, Dr. Robert Reiter suggested lutetium PSMA therapy as the next step, contingent on a PSMA PET scan confirming suitability. He emphasised the importance of PSMA uptake for therapy efficacy and discussed how tumour heterogeneity—such as low PSMA uptake in neuroendocrine variants—could affect treatment response. Dr. Priyamvada Maitre stressed the need for biopsy to guide salvage therapies if only the prostate recurs. The panel agreed that PSMA-positive metastatic sites are ideal targets for lutetium therapy, offering hope for further disease control.

Q&A Session Summary

Question 1:

Some patients present with full-blown metastasis without undergoing radical prostatectomy. In such cases, we performed radical prostatectomy, orchiectomy, and lutetium therapy, reporting success in 12 cases. Would you recommend radical prostatectomy upfront, or would you prioritise chemotherapy and lutetium therapy?

Answer:

Dr. Peter Hammerer: For high-volume metastatic disease, I would not recommend local therapy. However, in oligometastatic cases (1-2 bone or lymph node metastases), local therapy can be discussed. If radical prostatectomy is pursued, achieving negative margins is critical.

Dr. Robert Reiter: I agree. Additionally, next steps include genetic testing to check for HRR mutations to guide PARP inhibitor use. If the patient has bone metastases, radium-223 could also improve survival, as shown in a recent ESO trial.

Question 2:

If PSA rises after initial success with lutetium PSMA therapy, what would be your recommendation?

Answer:

Dr. Reiter: There are still multiple treatment options, such as cabazitaxel or radium-223. If the patient hasn't been exposed to docetaxel, that’s also a viable option.

Question 3:

What SUV cutoff is considered significant for PSMA PET in primary tumours? How do you explain SUV discordance between the primary tumour and metastases?

Answer:

Dr. Reiter: A relative cutoff of SUV >4 is often used, and anything above liver uptake is considered abnormal. Heterogeneity in PSMA uptake can reflect the tumour’s biology—for example, neuroendocrine variants may show low uptake despite aggressive behaviour.

Dr. Priyamvada Maitre: When planning salvage therapies, decisions shouldn't rely solely on SUV cutoffs. Biopsy remains essential for accurate diagnosis, especially if local recurrence is suspected. Higher PSMA uptake in metastases suggests active sites that are ideal targets for lutetium PSMA therapy.

Société Internationale d'Urologie Congress, 23-26 October 2024, New Delhi, India.