Evaluation of 68Ga-PSMA PET/CT Imaging for Preoperative Lymph Node Assessment in Intermediate and High-Risk Nonmetastatic Prostate Cancer

The primary objective of this study is to determine the **diagnostic performance** of Positron Emission Tomography with Prostate Specific Membrane Antigen Ligands (**PET-PSMA**) for detecting lymph node metastases in patients with intermediate or high-risk prostate cancer. This is clinically relevant as accurate detection of lymph node metastases is crucial for selecting appropriate radical treatment, such as prostatectomy, during multidisciplinary consultation meetings.

Secondary objectives include:

• Assessing the clinical impact of PET-PSMA on surgical strategy for lymph node dissection, particularly the extension to a suspected resectable area.
• Comparing MRI and PET-PSMA data with anatomopathological data for the prostate.
• Determining the positive predictive value of PET-PSMA for detecting distant visceral or bone metastases in patients selected for radical treatment by prostatectomy.
• Confirming data on the tolerance of 68Ga-HBED-CC-PSMA and 68Ga-PSMA-11.

The clinical trial focuses on **Prostate Cancer** and aims to evaluate the diagnostic performance of Positron Emission Tomography with Prostate Specific Membrane Antigen Ligands (PET-PSMA) for detecting lymph node metastases in patients with intermediate or high-risk prostatic neoplasia. The study population includes both male and female participants over the age of 18, with histologically confirmed prostatic neoplasia. Participants are selected based on their classification as having intermediate-risk neoplasia, characterized by a PSA level between 10 and 20 ng/mL, or high-risk neoplasia, with a PSA level of 20 ng/mL or higher, according to the d'Amico classification. The trial does not involve a vulnerable population, and all participants must be affiliated with or benefit from a health insurance scheme. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the **diagnostic performance** of Positron Emission Tomography with Prostate Specific Membrane Antigen Ligands (PET-PSMA) for detecting lymph node metastases in patients with intermediate or high-risk **prostate cancer**. This study is a **randomized, double-blind, controlled** trial, conducted over a period from May 2021 to May 2027. The trial involves the administration of two investigational products, 68GA-PSMA and Locametz, both delivered via **intravenous injection**. The primary objective is to assess the sensitivity, specificity, and likelihood ratios of PET-PSMA, using histological data and imaging follow-up as the gold standard.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histologically confirmed prostatic neoplasia, and risk classification according to the d'Amico classification. Follow-up visits will be scheduled to monitor the diagnostic outcomes and any adverse events. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and analyzed. The expected length of participant involvement is approximately six years, aligning with the trial's overall duration. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety.

Secondary endpoints include the modification of surgical strategies for lymph node dissection based on PET-PSMA results, the existence of pathological foci in various prostatic locations, and the positive predictive value of PET-PSMA in detecting distant metastases. Adverse events will be recorded throughout the trial to ensure participant safety. The trial is not classified as low intervention and is categorized as a Phase II clinical trial, indicating its exploratory nature in assessing the diagnostic capabilities of PET-PSMA in a specific patient population.

The clinical trial involves the administration of **68GA-PSMA**, a radiopharmaceutical agent used for diagnostic imaging. The active substance is chemically synthesized and is known as 2-[[5-[3-[[6-[[(5S)-5-CARBOXY-5-[[(1S)-1,3-DICARBOXYPROPYL]CARBAMOYLAMINO]PENTYL]AMINO]-6-OXOHEXYL]AMINO]-3-OXOPROPYL]-2-OXIDOPHENYL]METHYL-[2-[[5-(2-CARBOXYETHYL)-2-OXIDOPHENYL]METHYL-(CARBOXYLATOMETHYL)AMINO]ETHYL]AMINO]ACETATE:GALLIUM-68(3+) HYDRON, also referred to as 68GA-PSMA HBED-CC. The pharmaceutical form is an **injection**, administered via **intravenous injection**. The dosage is calculated based on the patient's weight, with a maximum daily and total dose of 5 MBq/kg. The treatment period is limited to a single day. Compliance with the dosing schedule is monitored through standard clinical trial procedures.

Additionally, the trial utilizes **Locametz 25 micrograms kit for radiopharmaceutical preparation**, which contains the active substance **gozetotide**. This product is also chemically synthesized and is provided as a **solution for injection**. The administration route is **intravenous injection**, with a maximum daily and total dose of 259 MBq. The treatment period is similarly restricted to one day. The preparation of the radiopharmaceutical is conducted according to the manufacturer's instructions, ensuring the correct dosage and administration. Participant compliance is monitored to ensure adherence to the dosing regimen.

The efficacy of the clinical trial will be assessed by evaluating the diagnostic performance of **Positron Emission Tomography with Prostate Specific Membrane Antigen Ligands (PET-PSMA)** for detecting lymph node metastases in patients with intermediate or high-risk nonmetastatic prostate cancer. The primary endpoint involves measuring the sensitivity, specificity, and likelihood ratios of PET-PSMA in detecting lymph node metastases, using histological data and/or imaging follow-up as the gold standard reference. Secondary endpoints include assessing the modification of surgical strategies for lymph node dissection based on PET-PSMA results compared to conventional imaging, identifying pathological foci across different examinations (PET-PSMA, MRI, and anatomopathology), and determining the positive predictive value of PET-PSMA in detecting distant visceral or bone metastases. Adverse events recorded during the assessment will also be considered. The trial aims to provide comprehensive data on the diagnostic accuracy and clinical utility of PET-PSMA in the pre-operative assessment of prostate cancer patients.