(UroToday.com) The 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 16th and 18th was host to a urothelial carcinoma rapid abstract session. Dr. Robert Huddart presented the results of RAIDER CRUK/14/016, a randomized phase II trial of adaptive image-guided standard or dose escalated tumor boost radiotherapy in the treatment of transitional cell carcinoma of the bladder.
Dr. Huddart began his presentation by highlighting the technical challenges of radiotherapy to the bladder given dynamic changes in the size and shape of the bladder throughout the day. For that reason, image-guided adaptive approaches to treatment, most commonly via a chosen “plan of the day treatment” with 3 separate plans chosen beforehand commonly developed, and the best one chosen each day.
In this study, the authors sought to evaluate whether these image-guided techniques would allow focusing of high dose volume on the tumor, while reducing the dose to the normal bladder, thus allowing for safe dose escalation in patients with bladder cancer.
To test this hypothesis, the authors designed a 2 stage non-comparative phase II study in parallel fractionation cohorts (64 or 70 Gy in 32 fractions and 55 or 60 Gy in 20 fractions). Patients with cT2-4aN0M0 unifocal urothelial bladder cancer suitable for radical chemoradiotherapy were randomized in a 1:1:2 fashion to either:
- Standard planning and delivery whole bladder RT (WBRT – control)
- Standard dose adaptive tumor focused RT (SART)
- Dose escalated adaptive tumor boost RT (DART)
Patients were randomized from 46 centers in the UK, Australia, and New Zealand. The primary endpoint was the proportion of patients experiencing any Grade 3+ radiotherapy related CTCAE late toxicity (6 to 18 months after radiotherapy). The investigators anticipated 8% Grade 3+ toxicity with WBRT, while wanting to exclude >20% receiving DART. At a 90% power with a 5% one-side alpha of 5%, this study required 57 evaluable DART patients (for each fractionation cohort). Secondary endpoints included clinician-reported late toxicity, locoregional disease control, and overall survival.
Baseline patient characteristics are demonstrated below and were well-balanced between the study arms. Of note, approximately 50% of patients received neoadjuvant chemotherapy, whereas approximately two thirds received concomitant chemotherapy.
An adaptive plan was required in about 60% of patients, with <2% of patients requiring only 1 plan.
With regards to the primary endpoint of any grade 3+ treatment emergent radiotherapy related late CTCAE toxicity (6-18 months), the investigators observed low levels of toxicity in the DART arm (none in the 32f arm and only 1.7% in the 20f arm), comparable to those seen in the WBRT arm. As the upper limit of the confidence interval (0.1 to 7.9%) did not cross the pre-defined mark of 20%, the primary outcome was achieved.
Similar results were seen for the late adverse events in the safety analysis population, with no worse toxicity profile for DART compared to the other radiotherapy arms as seen below. While we would have expected potentially worse GU toxicity profiles given the dose escalation to the bladder in the DART arm, this was not associated with worse GU toxicity.
With regards to local control, just under 60% of patients underwent a biopsy, with 87% overall demonstrating no evidence of residual disease at the 3-month timepoint.
At a median follow-up of 38.2 months for the 32f cohort and 42.1 months for the 20f cohort (as of May 17, 2022), the 3-year locoregional disease control rate was 79% in the WBRT/SART arm compared to 85% in the DART arm (HR: 0.74, 95% CI: 0.45 – 1.26, p=0.34). No significant differences in OS were noted (HR: 0.97, 95% CI: 0.67 – 1.40, p=0.65).
Dr. Huddart concluded his presentation as follows:
- Late grade 3+ toxicity was low in all treatment groups
- 20f and 32f DART was safe and feasible to deliver with toxicity rates below predefined thresholds
- Local control for image guided (chemo) radiotherapy was high and better than in historical studies
Presented by: Robert A Huddart, MBBS, FRCR, MRCP, PhD, The Institute of Cancer Research, Division of Radiotherapy and Imaging and The Royal Marsden Hospital, Radiotherapy Department, London, UK
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.