This phase II, registry-based cohort-multiple randomized controlled trial (cmRCT) evaluates whether daily online adaptive radiotherapy (ART) enables the safe delivery of hypofractionated, iso-biologically equivalent (EQD2) external beam radiotherapy compared with standard-of-care (SOC) fractionation.

Conventional radiotherapy requires generous planning target volume (PTV) margins to account for inter-fraction anatomical variation, which increases radiation exposure to surrounding organs at risk (OARs) and may contribute to toxicity. Modern ART platforms using daily on-table imaging (kV-CBCT or MRI guidance) allow real-time contour adaptation and online plan re-optimization based on same-day anatomy. This approach enables margin reduction while maintaining target coverage and may permit safe hypofractionation.

Eligible patients enrolled in an institutional prospective registry will be randomized (1:1) to receive either SOC radiotherapy or hypofractionated ART across multiple pelvic disease strata (post-prostatectomy prostate cancer, intact prostate cancer, endometrial cancer, cervical cancer, and rectal cancer).

The primary objective is to demonstrate non-inferiority of hypofractionated ART compared with SOC in terms of cumulative incidence of Grade ≥2 toxicity (CTCAE v5). Secondary outcomes include acute and late toxicity, oncologic outcomes (progression-free survival, locoregional failure, distant metastases, overall survival), patient-reported outcomes, treatment efficiency, and dosimetric parameters.

A Bayesian monitoring framework with pre-specified safety and futility stopping rules will be used to ensure patient safety and clinical equipoise throughout the trial.

Inclusion Criteria:

- Enrolled in PERa registry (CHUM CER 17.0.32), consented to contact for investigational trials, consented to serve as control, and randomly selected to be offered the experimental intervention.

Exclusion Criteria:

- For intact prostate stratum : 1. Contraindications to MRI (e.g., pacemaker, potentially mobile metal implant, claustrophobia). 2. Hip replacement, or other pelvic metalwork which causes significant artefact on MRI.