Abstract
Background
Two radiotherapy fractionation schedules are used for treating muscle invasive bladder cancer (MIBC): 64Gy in 32 fractions (f) over 6.5‐weeks and a hypofractionated schedule of 55Gy in 20f over 4‐weeks. Long‐term outcomes from several studies suggest that response, survival and toxicity are
comparable, but there is no direct comparison published. This work aimed to assess non‐inferiority (NI) of 55Gy/20f to 64Gy/32f in terms of invasive loco‐regional control (ILRC), and late toxicity in MIBC patients.
Methods
Individual patient data (IPD) for patients with invasive BC (T1G3, T2‐T4, N0, M0) were obtained from two multicentre randomised controlled trials: BC2001 (NCT00024349), assessing addition of chemotherapy to radiotherapy, and BCON (NCT00033436), which investigated combining hypoxiamodifying therapy with radiotherapy. In both trials, fractionation schedule was according to local
standard practice. Co‐primary endpoints were ILRC, rate free of muscle‐invasive bladder recurrence or recurrence in pelvic nodes (pre‐specified NI margin hazard ratio (HR) 1.25); and late bladder/rectal toxicity, assessed by LENT/SOMA (pre‐specified NI margin for absolute risk difference (RD) 10%) . Onestage IPD meta‐analysis models for time‐to‐event and binary outcomes were used, accounting for trial differences, within‐centre correlation, randomised treatment received, baseline imbalances and potential confounding from relevant prognostic factors.
Findings
782 patients (456 BC2001, 326 BCON; 376 64Gy/32f, 406 55Gy/20f) were included (mean age 72 years, 80% stage T1/2); median follow‐up was 120 months. Patients receiving 55Gy/20f had 29% lower risk of ILR recurrence than the 64Gy/32f schedule (adjusted HR=0.71 [95%CI: 0.52, 0.96]). Both schedules
had similar toxicity profiles, with 55Gy/20f having slightly lower risk (RD=‐3.37% [95%CI: ‐11.85%, 5.10%]) of grade 3/4 late bladder or rectum symptom than 64Gy/32f.
Interpretation
55Gy/20f is superior to 64Gy/32f for ILRC, and is non‐inferior in terms of toxicity and OS. 55Gy/20f should be adopted as standard of care for bladder preservation in this patient population.
Two radiotherapy fractionation schedules are used for treating muscle invasive bladder cancer (MIBC): 64Gy in 32 fractions (f) over 6.5‐weeks and a hypofractionated schedule of 55Gy in 20f over 4‐weeks. Long‐term outcomes from several studies suggest that response, survival and toxicity are
comparable, but there is no direct comparison published. This work aimed to assess non‐inferiority (NI) of 55Gy/20f to 64Gy/32f in terms of invasive loco‐regional control (ILRC), and late toxicity in MIBC patients.
Methods
Individual patient data (IPD) for patients with invasive BC (T1G3, T2‐T4, N0, M0) were obtained from two multicentre randomised controlled trials: BC2001 (NCT00024349), assessing addition of chemotherapy to radiotherapy, and BCON (NCT00033436), which investigated combining hypoxiamodifying therapy with radiotherapy. In both trials, fractionation schedule was according to local
standard practice. Co‐primary endpoints were ILRC, rate free of muscle‐invasive bladder recurrence or recurrence in pelvic nodes (pre‐specified NI margin hazard ratio (HR) 1.25); and late bladder/rectal toxicity, assessed by LENT/SOMA (pre‐specified NI margin for absolute risk difference (RD) 10%) . Onestage IPD meta‐analysis models for time‐to‐event and binary outcomes were used, accounting for trial differences, within‐centre correlation, randomised treatment received, baseline imbalances and potential confounding from relevant prognostic factors.
Findings
782 patients (456 BC2001, 326 BCON; 376 64Gy/32f, 406 55Gy/20f) were included (mean age 72 years, 80% stage T1/2); median follow‐up was 120 months. Patients receiving 55Gy/20f had 29% lower risk of ILR recurrence than the 64Gy/32f schedule (adjusted HR=0.71 [95%CI: 0.52, 0.96]). Both schedules
had similar toxicity profiles, with 55Gy/20f having slightly lower risk (RD=‐3.37% [95%CI: ‐11.85%, 5.10%]) of grade 3/4 late bladder or rectum symptom than 64Gy/32f.
Interpretation
55Gy/20f is superior to 64Gy/32f for ILRC, and is non‐inferior in terms of toxicity and OS. 55Gy/20f should be adopted as standard of care for bladder preservation in this patient population.
| Original language | English |
|---|---|
| Journal | Lancet Oncology |
| DOIs | |
| Publication status | Published - 1 Feb 2021 |
Research Beacons, Institutes and Platforms
- Manchester Cancer Research Centre
