177 Lu-PSMA With Olaparib Radiosensitization Potentiates Response and Toxicity in Extensive Castration-Resistant...

Area of Science:

• Oncology
• Nuclear Medicine
• Medical Physics

Background:

• Advanced prostate cancer with bone metastases and BRCA mutations presents therapeutic challenges.
• Patients often progress despite multiple lines of standard treatment.
• Prostate-specific membrane antigen (PSMA) targeted radionuclide therapy is an emerging treatment modality.

Purpose of the Study:

• To evaluate the efficacy and toxicity of 177Lu-PSMA therapy combined with olaparib radiosensitization in a patient with metastatic prostate cancer.
• To assess the predictive value of dosimetry in the context of radiosensitizer use.

Main Methods:

• A single patient with widespread PSMA-expressing, BRCA-mutated bone metastases received 177Lu-PSMA therapy (8.5 GBq).
• A short course of olaparib was administered concurrently as a radiosensitizer.
• Tumor response was assessed by PSA level decrease and response better than predicted by dosimetry.
• Marrow toxicity was evaluated based on clinical presentation and hospitalization.

Main Results:

• A 90% decrease in serum PSA level was achieved after a single 177Lu-PSMA treatment.
• Tumor response significantly exceeded predictions based on dosimetry.
• Unexpectedly severe marrow radiotoxicity occurred, necessitating hospitalization.
• Olaparib acted as a radiosensitizer, enhancing both tumor response and toxicity.

Conclusions:

• 177Lu-PSMA therapy combined with olaparib radiosensitization can yield substantial tumor response in advanced prostate cancer.
• Radiosensitizing agents represent a double-edged sword, significantly increasing toxicity alongside efficacy.
• Careful consideration and balancing of activity prescription are crucial when using radiosensitizers to mitigate adverse events.