Long-term QoL data support adding chemo to RT for localized MIBC

Previously reported efficacy data from BC2001, a phase III randomized trial of bladder-sparing treatment for localized muscle-invasive bladder cancer, showed that adding chemotherapy to radiotherapy significantly reduced the chance of the cancer returning in the bladder.

Newly reported analyses of data collected over 5 years of follow-up using the Functional Assessment of Cancer Therapy-Bladder (FACT-BL) questionnaire show that following an expected immediate decline following radiotherapy, health-related quality of life (HRQoL) is not decreased persistently following bladder-sparing treatment, nor is it significantly worsened by concomitant chemotherapy. 

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The findings were published in European Urology (2020; 77:260-8). The joint first authors are Robert A. Huddart, MD, PhD, and Emma Hall, PhD, of The Institute of Cancer Research, London. Dr. Huddart told Urology Times, “There has been a view that radiotherapy has a detrimental effect on quality of life because it causes significant bladder damage. Our study, which is by far the most comprehensive and largest study of the quality of life of patients who received bladder radiotherapy, shows that is not the case. Although patients overall experienced an initial decline in HRQoL due to the early side effects of their treatment, average quality of life measures returned to baseline during ongoing follow-up and remained at or above the pretreatment level. Furthermore, we found on average no evidence of any detrimental effects on bowel, bladder, or sexual function.”

“As another take-home message, our study showed that at least with the regimen used in our trial, patients can have chemotherapy in addition to radiotherapy without any fear that it will impair their quality of life.”

Patients enrolled in BC2001 had T2-T4a N0 M0 transitional cell carcinoma of the bladder. Under a 2x2 partial factorial design, they could be randomized 1:1 to receive radiotherapy alone or combined with chemotherapy (chemoradiation comparison); they could also be randomized 1:1 to receive standard whole-bladder radiotherapy or reduced high-dose volume radiotherapy with tumor boost (radiotherapy comparison). All patients received conformal radiotherapy on consecutive weekdays (55 Gy/20 fractions or 64 Gy/32 fractions as per local site preference). The chemotherapy regimen was mitomycin C, 12 mg/m² on day 1 of radiotherapy and 5-fluorouracil, 500 mg/m² infused over 24 hours for 5 days during radiotherapy fractions 1-5 and 16-20.

The FACT-BL questionnaire was completed at baseline, end of treatment, and at 6, 12, 24, 36, 48, and 60 months after radiotherapy. Change from baseline to 12 months in the bladder cancer subscale (BLCS) was defined as the primary endpoint.

Next: Mean BLCS not significantly decreased at 12 monthsIn the overall population, there was a statistically significant mean decrease in the BLCS score from baseline to the end of treatment visit, but the mean BLCS recovered thereafter and was not significantly decreased at 12 months.

Additional analyses found no statistically significant differences between randomized groups at any of the follow-up visits in the mean BLCS score nor in any other FACT-BL subscale scores (physical well-being, functional well-being, social well-being, emotional well-being).

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An analysis of individual patient scores rather than the total population means, however, showed that although most patients reported stable or even improved HRQoL on follow-up, up to 30% of patients reported a decline. The proportions of patients reporting changes that would be considered clinically relevant did not differ significantly between treatment groups in randomized comparisons for any of the questionnaire subscales at any time point.

“The cause for a persistent decline in some patients is not currently known, but it is something that we are evaluating further. In particular, we want to find out if there is anything that can be done to prevent or reverse the decline,” said Dr. Huddart.

“If useful interventions could be identified, their application would make the results from combined chemotherapy and radiotherapy even better.”