Overview
TACTIC-P is a single-center, prospective, single-arm study in 12 men with biopsy-proven prostate cancer and pelvic lymph-node uptake on preoperative PSMA PET, without bone or visceral metastases, who are scheduled for robot-assisted radical prostatectomy and extended pelvic lymph-node dissection. On the day of surgery, participants receive intravenous gallium-68 PSMA-11 followed by PET/CT and PSMA-radioguided surgery using a drop-in gamma probe. Resected prostate tumor, metastatic lymph-node tissue, and matched blood samples are used for high-dimensional immune profiling. The main goal is to determine whether functional pathogen-specific bystander tissue-resident T cells can be identified and quantitatively characterized in the primary tumor and/or metastatic lymph nodes. The study also evaluates immune features relevant to future personalized immunotherapy, the ability of PSMA-radioguided surgery to detect pathologically positive lymph nodes, and perioperative safety through 12 weeks after surgery.
Description
This exploratory mechanistic study investigates tissue-resident bystander T cells in node-positive prostate cancer and the feasibility of using their molecular and functional features to inform personalized immunotherapeutic strategies. All participants undergo the same study pathway. On Day 0, gallium-68 PSMA-11 is administered intravenously (approximately 1.8-2.8 MBq/kg; standard activity approximately 160 MBq). PET/CT is performed approximately 60 minutes after tracer administration. Robot-assisted PSMA-radioguided surgery is then performed 4-8 hours after injection using a drop-in gamma probe. A positive intraoperative finding is defined as a count rate at least twice the background reference. PSMA-positive lesions are excised, followed by anatomically defined extended pelvic lymph-node dissection and Retzius-sparing robot-assisted radical prostatectomy.
Fresh primary tumor, metastatic lymph-node tissue, FFPE tissue, and matched peripheral blood are collected. The first six participants are used primarily to optimize tissue acquisition and molecular workflows. The subsequent six participants expand the patient-derived tumor fragment platform and ex vivo immunological testing. Molecular analyses include scRNA-seq, scCITE-seq, scTCR-seq, bulk TCR sequencing, functional stimulation with common viral peptide pools, cytokine/chemokine assays, and spatial profiling. Functional bystander tissue-resident T cells are defined using integrated evidence of tissue detection, a resident/non-naive phenotype, ex vivo activation or proliferation after pathogen-derived peptide stimulation, and TCR clonotype identification.
Participants are followed at Day 28 and Day 84 for laboratory tests, adverse events, perioperative outcomes, pathology, and postoperative data. The study is hypothesis-generating and is not powered for confirmatory clinical efficacy testing.
Eligibility
Inclusion Criteria:
- Male participants.
- Age 18 to 85 years.
- Biopsy-proven prostate cancer with positive lymph nodes on staging PSMA PET (miN+).
- Planned robot-assisted radical prostatectomy with extended pelvic lymph-node dissection.
- Able to understand and willing to sign written informed consent.
Exclusion Criteria:
- Neoadjuvant hormonal therapy before surgery.
- Inability to complete imaging examinations according to the protocol.
- Bone or visceral metastatic disease (M1b-c) on preoperative imaging.
- Life expectancy \<12 months.
- Previous chemotherapy.
- Previous brachytherapy or external-beam radiotherapy.
- Congestive heart failure.
- Any other significant disease/disorder that, in the investigator's opinion, may increase risk, influence study results, or impair participation.
- History of allergic disease/reactions likely to be exacerbated by study IMPs or radiotracer components (68Ga-PSMA).
- Experimental drug within 30 days before radiotracer administration or within 5 half-lives of that experimental drug.
