Prostate Stereotactic Radiation and Radio-induced Lymphocyte Apoptosis for Predicting Late Toxicities in Prostate Cancer (PROSTERA)

PROSTERA is a prospective, single-arm, monocentric interventional study (RIPH-2) designed to evaluate the prognostic performance of the Radio-induced Lymphocyte Apoptosis (RILA) assay to predict late radiation-induced toxicities in patients with localized prostate cancer treated with stereotactic body radiotherapy (SBRT).

The primary objective is to determine whether pre-treatment RILA (percentage of apoptotic T-lymphocytes measured ex-vivo after controlled irradiation) is predictive of clinically meaningful late toxicities graded ≥2 according to CTCAE v5.0 within 24 months after SBRT. Secondary objectives include PSA kinetics, patient-reported outcomes (EORTC QLQ-PR25, QLQ-C30 and IPSS), dosimetric correlations, and estimation of diagnostic performance metrics (AUC, sensitivity, specificity) of the RILA assay.

A single peripheral blood sample (2 mL) is collected at the time of CT simulation (inclusion visit). Samples are transported to the designated laboratory (LIRS/RunResearch) and processed according to the RILA SOP: cells are placed in culture (RPMI 1640 + 20% FBS, dilution 1:10) within 4 hours of collection, incubated 16-24 hours, then irradiated ex-vivo (8 Gy; conformational irradiation using institutional accelerator) and incubated for an additional 48 hours. After post-irradiation incubation cells are stained for CD4/CD8 and propidium iodide and analysed by flow cytometry (FACS) on 10,000 events in triplicate to derive the percentage of apoptotic CD4+ and CD8+ T-cells. All assay timings and plate/aliquot identifiers are recorded in laboratory logs. The collected sample is entirely consumed for the assay (no sample retention).

Eligible participants are adult males with localized prostate adenocarcinoma meeting the protocol inclusion criteria (e.g. clinical stage T1-T2, Gleason score 6-7, PSA <15 ng/mL as per protocol), able to provide written informed consent and compliant with follow-up procedures. Key exclusions include prior pelvic radiotherapy, metastatic disease, inability to consent, and other criteria listed in the protocol. Enrollment will be consecutive to limit selection bias.

All participants receive SBRT delivered according to institutional conformational technique (protocol-specified dose constraints and organ-at-risk delineation per RTOG recommendations; typical stereotactic schedule described in the protocol). Imaging data (centering CT and any low-dose CT), treatment plans and dose-volume histograms (DVH) will be collected and stored in the electronic CRF for dose-toxicity correlation analyses.

Safety and patient-reported outcomes will be recorded during routine follow-up visits at baseline (pre-SBRT) and at 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 months post-radiotherapy; CTCAE v5.0 will be used for toxicity grading and the EORTC QLQ-PR25, QLQ-C30 and IPSS questionnaires for quality-of-life and urinary symptom assessment. PSA will be measured at the same scheduled timepoints. No additional study-specific clinic visits are required beyond standard care.

The planned sample size is 220 subjects (calculated to achieve the desired precision for the RILA AUC estimate; ~166 evaluable subjects minimally required), with an anticipated inclusion period of 24 months and maximum individual follow-up of 61 months (total study duration ≈ 88 months). Data will be recorded in a pseudonymized electronic CRF and source documents will remain available in patient medical records. The study will be conducted under the applicable ethical and regulatory framework (CPP approval, MR-001, GDPR).

Inclusion criteria

• Male, aged 60 years or older, presenting with localized prostate cancer of low or intermediate risk (T1-T2 stage, Gleason score 6-7, and PSA <15 ng/mL) without metastatic disease, and for whom radiotherapy is indicated.
• Patient affiliated with, or beneficiary of, the French national health insurance system.
• French-speaking patient.
• Patient who has been informed about the study and has provided written informed consent.

Exclusion criteria

• Patient unable to read, write, or understand French.
• Vulnerable patient as defined in Article L1121-6 of the French Public Health Code.
• Adult under legal guardianship, curatorship, or judicial protection.
• Patient unable to personally provide informed consent as per Article L1121-8 of the French Public Health Code, or adult protected by law.
• Patient already enrolled in an interventional study that could influence the outcomes of the present study.
• Patient with a history of prostate and/or digestive surgery.
• Refusal to sign the written informed consent at inclusion.