(UroToday.com)The 2023 ASTRO annual meeting included a session on clinical trials in prostate cancer, featuring a presentation by Dr. Ragu Ratnakumaran discussing results of the association between acute and late genitourinary and gastrointestinal toxicities, an analysis of the PACE B study. Acute gastrointestinal and genitourinary toxicity after prostate radiotherapy has been shown to be associated with late toxicity with 3D conformal radiotherapy.
This association may be due to significant baseline symptoms, genetic factors, dosimetric risk factors, and/or consequential late effects. However, whether this association is present with modern approaches, such as stereotactic body radiotherapy, remains unclear. Dr. Ratnakumaran and colleagues analyzed patients treated within the PACE-B international phase III non-inferiority randomized control trial to assess the association between acute and late toxicity following stereotactic body radiotherapy and conventional/moderately hypofractionated radiotherapy. They hypothesize that acute toxicity is significantly associated with equivalent late toxicity following prostate stereotactic body radiotherapy and conventional/moderately hypofractionated radiotherapy.
The trial design for the PACE-B trial is as follows, with the 2-year toxicity outcomes already published:1
Dr. Ratnakumaran and colleagues analyzed patients with gastrointestinal and Genitourinary Common Terminology Criteria for Adverse Events (CTCAE) measurements in the acute (<=12 weeks post- radiotherapy) and late period (6-24 months post-radiotherapy). Using logistic regression, they analyze the association between G2+ acute gastrointestinal and genitourinary toxicities with equivalent late toxicities. Lasso variable selection was used to determine patient, tumor and treatment variables to include in the multivariable model (patient age, NCCN risk group, prostate volume, fiducial use, alpha blocker/anticholinergic use before randomization, and stereotactic body radiotherapy modality). The area under the receiver operator characteristics curve (AUC) was used to evaluate the model’s predictive performance. Of patients included in this analysis (n=842), 414 were treated with stereotactic body radiotherapy and 428 with conventional/moderately hypofractionated radiotherapy. The baseline features for these patients is as follows:
The following is the stacked bar graph for maximum grade CTCAE late genitourinary toxicity experienced for patients with grade 0-1 and grade 2+ baseline symptoms (left) and grade 0-1 and grade 2+ acute toxicity (right):
In univariable analysis, G2+ acute genitourinary toxicity was significantly associated with developing G2+ late genitourinary toxicity after stereotactic body radiotherapy (OR 4.63, 95% CI 2.96-7.25). This association remained significant in multivariable analysis (OR 3.70, 95% CI 2.39-5.98). The models AUC for predicting G2+ late genitourinary toxicity after stereotactic body radiotherapy was 0.73 (95% CI, 0.67-0.78) and 0.66 (95% CI, 0.59-0.73) following conventional/moderately hypofractionated radiotherapy.
The following is the stacked bar graph for maximum grade CTCAE late gastrointestinal toxicity experienced for patients with acute grade 0-1 (left) and grade 2+ (right) toxicity:
In univariable analysis, G2+ acute gastrointestinal toxicity was associated with developing G2+ late gastrointestinal toxicity after stereotactic body radiotherapy (OR 3.67, 95% CI 1.91-7.03) and conventional/moderately hypofractionated radiotherapy (OR 4.4, 95% CI 2.04-9.47). This association also remained significant in multivariable analysis (stereotactic body radiotherapy: OR 3.68, 95% CI 1.89-7.17; conventional/moderately hypofractionated radiotherapy: OR 4.61, 95% CI 2.11-10.06). The models AUC for predicting G2+ late gastrointestinal toxicity after stereotactic body radiotherapy was 0.66 (0.95% CI, 0.57-0.75) and 0.64 (95% CI, 0.57-0.72) following conventional/moderately hypofractionated radiotherapy.
Dr. Niazi concluded this presentation discussing results of the association between acute and late genitourinary and gastrointestinal toxicities, an analysis of the PACE B study with the following take-home points:
- Baseline urinary symptoms and acute urinary toxicity are significantly associated with late urinary toxicity following stereotactic body radiotherapy and conventional/moderately hypofractionated radiotherapy
- Acute bowel toxicity is significantly associated with late bowel toxicity following stereotactic body radiotherapy and conventional/moderately hypofractionated radiotherapy
- Future work should test whether optimizing symptoms pre-treatment/early intervention in those with significant acute toxicities could mitigate the development of late toxicity
- In those with severe genitourinary symptoms at baseline, one could offer moderate hypofractionation in preference to stereotactic body radiotherapy
Presented by: Ragu Ratnakumaran, Royal Marsden NHS Foundation Trust, Sutton, UK
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 American Society of Radiation Oncology (ASTRO) Annual Meeting, San Diego, CA, Sun, Oct 1 – Wed, Oct 4, 2023.
Related Content: PACE B Study Analysis: Acute and Late Toxicities in Prostate Cancer Radiotherapy - Ragu Ratnakumaran
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