(UroToday.com) On Sunday, September 11,2022, in the Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers, Dr. Tim Smith presented a post-hoc aggregate analysis of the BC2001 and BCON trials aimed at assessing the effect of tumor hypoxia on radiotherapy fractionation schedules. Standard of care treatment for patients with muscle-invasive bladder cancer (MIBC) includes radical cystectomy or radiotherapy with radiosensitizing systemic therapy.
In the context of the BCON trial, the West 24-gene bladder cancer hypoxia signature predicted benefit from hypoxia-modifying radiosensitization (carbogen+nicotinamide, CON). In the BC2001 trial, the addition of chemotherapy (5-FU, mitomycin-C) to radiotherapy (RT) was shown to improve loco-regional progression free survival. Both of these trials allowed conventional (62Gy/32 fractions) or hypofractionated (55Gy/20 fractions) RT. In this pooled analyses of these two trials, the authors tested two hypotheses:
(1) the hypoxia signature does not predict benefit from concurrent chemotherapy;
(2) accelerated treatment (ie. hypofractionation) reduces reoxygenation and is less favourable for patients with hypoxic tumours.
The authors obtained signatures from patients in both trials including previously published data from patients in BCON (n=151) and post-hoc analysis of patients in BC2001 (n=312). Among patients in the BC2001 trial, pre-treatment biopsy samples underwent RNA extraction with subsequent full transcriptomic data generated using Affymetrix Clariom S arrays. Patients were stratified using the cohort median of the median expression of 24-signature genes hypoxia score into hypoxia-high and -low groups.
In the pooled analysis, the authors demonstrated that the hypoxia score was prognostic for overall survival in both univariable and multivariable (HR=1.29; 95% CI 0.97-1.71; p=0.075) analyses with no interaction between hypoxia score and treatment arm (p=0.92)
Patients with hypoxic tumours had a poorer prognosis following hypofractionated compared with conventional fractionated radiotherapy in both BC2001 (n=298, HR 1.80 95% CI 1.08-2.91; p=0.023) and the BCON RT only arm (n=75; HR 14.2; 95% CI 1.7-119; p=0.015).
However, in the context of the BCON trial, the use of CON negated the detrimental effect of hypoxia with hypofractionated RT.
Thus, Dr. Smith concluded that, while hypoxic MIBC has a poor prognosis and exhibits fraction sensitivity, this is mitigated with hypoxia modification. Thus, a hypoxia score may be used to personalise treatment.
Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.