RCMIGI trial supports feasibility of reduced margins in image-guided prostate radiotherapy

Data published in Radiotherapy and Oncology add to the growing body of evidence on the feasibility and potential benefits of margin reduction during radiation therapy treatment.

The findings, which come from the phase 2 RCMIGI trial (NCT03254420), suggest that intensity-modulated (IMRT) and image-guided (IGRT) radiotherapy with reduced target margins may improve some dosimetric parameters and patient-reported urinary symptoms compared with conventional IMRT/IGRT in patients with low- to intermediate-risk prostate cancer.¹

“Recent advances in radiotherapy, including IMRT and IGRT, offer improved protection of healthy tissues surrounding the target and help minimize radiation-induced toxicities,” the authors wrote. “Nonetheless, treatment margins—planning target volumes (PTV)—remain essential to account for inter- and intra-fractional target motion and residual uncertainties, ensuring accurate dose delivery even when IGRT is combined with adaptive radiotherapy.”

For the study, the investigators randomly assigned 74 patients in a 1:2 fashion to either IMRT/IGRT with standard (control; n = 30) or reduced (experimental; n = 44) margins. Patients in the control arm received IGRT treatment plus cone-beam computed tomography (CBCT), whereas patients in the experimental arm received IGRT plus CBCT combined with real-time tracking using the Calypso System. The Calypso System is “a real-time target tracking system that takes into account both inter- and intrafractional target motion” using “electromagnetic transponders implanted within the prostate.”

In the study, 92.9% of patients (n = 65) received conventional fractionation (80 Gy in 40 fractions) and 5 patients received moderate hypo-fractionation (62 Gy in 20 fractions).

According to the authors, baseline and tumor characteristics were well balanced between the 2 treatment arms. The median age of participants was 69.5 years. The primary end point was the incidence of grade 2 or greater late pelvic toxicity between 3 and 24 months after radiotherapy.

Five patients in each treatment arm experienced grade 2 or higher late pelvic toxicity during the follow-up period. In the experimental arm, 6.8% of patients experienced grade 2 or higher genitourinary toxicities and 4.6% experienced grade 2 or higher gastrointestinal toxicities, compared with rates of 19.2% and 0% in the control arm, respectively. Overall, 88.6% (95% CI, 75.4 to 96.2) of patients in the experimental arm and 80.8% (95% CI, 60.6 to 93.4) of patients in the control arm did not experience a grade 2 or higher late pelvic toxicity during the follow-up period.

Among patients who received conventional fractionation (n = 65), those in the experimental arm showed significantly lower doses for rectal V_70Gy and D_50% (P < .01) and for bladder D_50%, V_70Gy, and V_76Gy (P < .01). However, doses for rectal D_1% and V_76Gy, and bladder V_80Gy were significantly higher (P < .01) in the experimental arm.

At 5 years, the overall survival was 91.8% (95% CI, 69.8 to 98.0) in the experimental arm vs 100% in the control arm. Five-year biochemical recurrence-free survival was 82.1% (95% CI, 56.9 to 93.3) in the experimental arm and 100% in the control arm. The 2-year complication relapse-free survival rates were 84.9% (95% CI, 69.4 to 92.9) and 92.0% (95% CI, 71.5 to 97.9), respectively.

Patient-reported urinary symptoms, assessed via QLQ-PR25 scores, were generally higher among patients in the control arm. This trend started at 3 months and persisted up to 2 years. The authors noted, “While these differences were not statistically significant at most follow-up visits (P > .05), a significant difference was observed at the 2-year follow-up, with mean scores of 21.2 in the control arm and 12.3 in the experimental arm (P = .028).”

QLQ-C30 functional scores were consistently high over time across both study arms.

“While non-invasive alternatives, including advancements in on-board imaging and adaptive radiotherapy, represent the future of radiotherapy, margin reduction remains a fundamental principle of precision radiotherapy,” the authors wrote. “Our findings may be relevant to emerging technologies in radiotherapy that allow tighter margins while preserving organ-at-risk integrity.”

They also concluded, “These results reinforce the value of precise image guidance for safely reducing treatment margins.”

REFERENCE

1. Riou O, Fenoglietto P, Jarlier M, et al. Image-guided intensity-modulated radiotherapy with reduced margins in patients with prostate cancer: Results of the RCMIGI randomized phase II trial. Radiother Oncol. 2025:215:111322. doi:10.1016/j.radonc.2025.111322