Chemoradiotherapy Offers Improved Locoregional Control, Cystectomy Rates in MIBC

Chemoradiotherapy Offers Improved Locoregional Control, Cystectomy Rates in MIBC

Prof. Emma Hall
After a median 10 years of follow-up, the BC2001 trial confirmed that adding chemotherapy to radiotherapy (RT) improves salvage cystectomy rate, locoregional control, and bladder cancer–specific survival over RT alone in muscle-invasive bladder cancer (MIBC; Abstract 280).

The BC2001 trial included 458 patients, randomly selected in a 2 x 2 partial factorial design, to receive either chemoradiotherapy with 5-fluorouracil and mitomycin C (5FU-MMC) or RT alone. A second, separate randomization divided patients into standard-volume RT and reduced high–dose volume RT, which closed early due to poor accrual; about a quarter of the patients participated in both parts of the trial.

Initial results of this study were published in 2012 in The New England Journal of Medicine, after a median 70.3 months of follow-up.1 The study showed improved locoregional control with chemoradiotherapy over RT. Unsurprisingly, due to the poor accrual, that analysis was unable to conclude that the reduced high–dose volume RT was non-inferior. The new analysis, presented by Emma Hall, PhD, of the Institute of Cancer Research, in London, extended the follow-up out to a median of 118.2 months.

Patients had a median age at randomization of 72.9 years, and most were male (80.8%). Most patients had a pathologic stage of T2 (83.3%), and most did not have residual mass after resection (70.8%).

The new analysis confirmed that chemoradiotherapy offers better locoregional control over RT alone. The adjusted hazard ratio (HR) for locoregional control was 0.59 (95% CI [0.41, 0.83]; p = 0.003). This was also true specifically for invasive locoregional control, with an adjusted HR of 0.52 (95% CI [0.33, 0.81]; p = 0.004).

Differences with regard to overall survival did not reach statistical significance, although Prof. Hall said there was “a hint of a separation of those curves,” with an adjusted HR in favor of chemoradiotherapy of 0.81 (95% CI [0.62, 1.04]; p = 0.100). After adjustment for known prognostic factors, bladder cancer–specific survival was better with chemotherapy, with an HR of 0.73 (95% CI [0.54, 0.99]; p = 0.043).

The 2-year rate of salvage cystectomy was 11% with chemotherapy and 17% without it. At 5 years, these rates were 14% and 22%, respectively, for an HR of 0.54 (95% CI [0.31, 0.95]; p = 0.03).

The updated analysis comparing the two dosing schedules of RT again showed no differences between standard and reduced high-volume dose. Over the full follow-up period, 14.9% of patients receiving the standard dose and 19.4% of patients receiving the reduced high-volume dose had grade 3 or higher toxicity (p = 0.47). The locoregional control rates were no different based on dosing, nor were metastasis-free, overall, or bladder cancer–specific survival rates. Prof. Hall noted that with only two extra events accruing since the last analysis of the RT volumes, this is unlikely to change further over time.

“With 10 years of follow-up, we have seen an improvement in locoregional control and a reduced salvage cystectomy rate, confirmed with chemoradiotherapy,” Prof. Hall said. “If you take that together with the good quality of life that we’ve seen, we think this is important in this patient group.” She added that the long-term data are robust and support the use of chemoradiotherapy with 5FU-MMC as a standard treatment in MIBC.

Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, was the discussant for the abstract. He agreed that these data confirm the therapy’s utility in this patient population and added that better selection of patients will be useful. “DNA repair mechanisms are potentially important as predictive markers,” he said, noting that the protein MRE11—which is part of a complex that senses DNA breaks and is involved in repair—is under study as one such marker of DNA repair.

– David Levitan