Elective pelvic nodal irradiation in the setting of ultrahypofractionated versus moderately hypofractionated and conventionally fractionated radiotherapy for prostate cancer: Outcomes from 3 prospective clinical trials

Rachel M Glicksman; Andrew Loblaw; Gerard Morton; Danny Vesprini; Ewa Szumacher; Hans T Chung; William Chu; Stanley K Liu; Chia-Lin Tseng; Melanie Davidson; Andrea Deabreu; Alexandre Mamedov; Liying Zhang; Patrick Cheung

doi:10.1016/j.ctro.2024.100843

Elective pelvic nodal irradiation in the setting of ultrahypofractionated versus moderately hypofractionated and conventionally fractionated radiotherapy for prostate cancer: Outcomes from 3 prospective clinical trials

Clin Transl Radiat Oncol. 2024 Aug 16:49:100843. doi: 10.1016/j.ctro.2024.100843. eCollection 2024 Nov.

Authors

Rachel M Glicksman^{1

2}, Andrew Loblaw^{1

3

4}, Gerard Morton^{1

3}, Danny Vesprini^{1

3}, Ewa Szumacher^{1

3}, Hans T Chung^{1

3}, William Chu^{1

3}, Stanley K Liu^{1

3}, Chia-Lin Tseng^{1

3}, Melanie Davidson⁵, Andrea Deabreu⁶, Alexandre Mamedov⁶, Liying Zhang⁶, Patrick Cheung^{1

3}

Affiliations

¹ Department of Radiation Oncology, University of Toronto, Toronto, Canada.
² Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
³ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Canada.
⁵ Department of Medical Physics, Kelowna General Hospital, BC Cancer, Kelowna, Canada.
⁶ Clinical Trials and Epidemiology Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.

Abstract

Background and purpose: Data is needed regarding the use of ultrahypofractionated radiotherapy (UHRT) in the context of prostate cancer elective nodal irradiation (ENI), and how this compares to conventionally fractionated radiotherapy (CFRT) ENI with CFRT or moderately hypofractionated radiotherapy (MHRT) to the prostate.

Materials and methods: Between 2011-2019, 3 prospective clinical trials of unfavourable intermediate or high-risk prostate cancer receiving CFRT (78 Gy in 39 fractions to prostate; 46 Gy in 23 fractions to pelvis), MHRT (68 Gy in 25 fractions to prostate; 48 Gy to pelvis), or UHRT (35-40 Gy in 5 fractions to prostate +/- boost to 50 Gy to intraprostatic lesion; 25 Gy to pelvis) were conducted. Primary endpoints included biochemical failure (Phoenix definition), and acute and late toxicities (CTCAE v3.0/4.0).

Results: Two-hundred-forty patients were enrolled: 90 (37.5 %) had CFRT, 90 (37.5 %) MHRT, and 60 (25 %) UHRT. Median follow-up time was 71.6 months (IQR 53.6-94.8). Cumulative incidence of biochemical failure (95 % CI) at 5-years was 11.7 % (3.5-19.8 %) for CFRT, 6.5 % (0.8-12.2 %) MHRT, and 1.8 % (0-5.2 %) UHRT, which was not significantly different between treatments (p = 0.38). Acute grade ≥ 2 genitourinary toxicity was significantly worse for UHRT versus CFRT and MHRT, but not for acute grade ≥ 3 genitourinary, or acute gastrointestinal toxicities. UHRT was not associated with worse late toxicities.

Conclusion: ENI with UHRT resulted in similar oncologic outcomes to CFRT ENI with prostate CFRT/MHRT, with worse acute grade ≥ 2 GU toxicity but no differences in late toxicity. Randomized phase 3 trials of ENI using UHRT techniques are much anticipated.

Keywords: Elective nodal irradiation; High-risk prostate cancer; Stereotactic body radiotherapy; Ultrahypofractionation.