INSPIRE: INnovative SABR for Prostate Cancer All IREland

This is a Phase II, single arm, multi-centre, prospective clinical trial evaluating next generation Stereotactic Ablative Radiotherapy (SABR) for low, intermediate, and eligible high-risk prostate cancer. Eligible patients will receive next generation prostate SABR incorporating toxicity reduction strategies: urethral/trigone sparing, rectal hydrogel spacer, and neurovascular bundle preservation \[as per Desai POTEN-C trial, Desai et al., 2025\]. Treatment will prioritise the dominant intraprostatic lesion (DIL) while sparing surrounding organs at risk (OARs). Planned doses are: DIL 40-50 Gy in 5 fractions delivered on alternate days, prostate CTV 35 Gy, PTV 33.25 Gy, and urethral PRV 32.5 Gy. Eligible high-risk and some intermediate-risk patients may receive 6-12 months of androgen deprivation therapy (ADT)/hormonal therapy at the physician's discretion, provided they have not received \>14 weeks prior to registration. Radiotherapy planning will include advanced image-guided verification with fiducial markers, pre-treatment dosimetry to minimise dose to OARs, and adherence to protocol-defined constraints for urethra, rectum, and neurovascular bundles. Peri-rectal spacers will be inserted 7-10 days prior to CT-simulation to reduce rectal dose. Dose prioritisation allows full coverage of the DIL while sparing urethra, bladder trigone, and neurovascular bundles to minimise genitourinary, rectal, and sexual toxicity. Follow-up assessments will include clinical evaluation, toxicity reporting using v5 NCI CTCAE, and patient-reported outcome measures (PRO/QoL) at 2-, 4-, 8-, and 12-weeks post-treatment, 6 and 9 months, and annually up to 5 years. Data on biochemical/clinical failure, progression-free survival, and initiation or re-initiation of ADT will also be collected. A total of 136 patients will be enrolled to achieve 122 evaluable participants, allowing detection of a statistically significant reduction in Grade ≥2 late genitourinary toxicity compared to historical SABR controls.