Episode 7: Chemoradiotherapy emerges as a viable option for bladder sparing treatment in MIUC

In this episode of WND, Prof Emmanuel Seront from UCL Louvain and Prof Vulsteke from Maria Middelares Gent are engaged in a discussion regarding a recent phase 2 study that adds checkpoint inhibition to chemoradiation for the treatment of muscle-invasive urothelial cell carcinoma (MIUC).

Currently, two treatment options are available for MIUC: chemotherapy followed by radical cystectomy or chemoradiotherapy, which offers a promising alternative by sparing the bladder. Local treatment can achieve a pCR, thus avoiding cystectomy. At ASCO 2023, a phase 2 study was presented, evaluating the combination of the immune checkpoint inhibitor pembrolizumab with trimodality therapy (TMT), consisting of maximal transurethral resection of bladder tumour (TURBT), hypofractionated radiotherapy, and twice-weekly gemcitabine (gem).

The study design included one cycle of pembrolizumab, followed by maximal TURBT, four weeks of radiotherapy with low-dose gemcitabine, and three cycles of pembrolizumab. Patients included those with pure MIUC or mixed urothelial carcinoma with clinical T2-T4aN0M0 MIUC who were ineligible for or declined radical cystectomy. This regimen proved feasible for all patients, as most completed treatment without toxicity.

The primary endpoint was 2-year bladder-intact disease-free survival (BIDFS), including new episodes of MIUC, nodal or distant metastases, cystectomy, progression or death. Secondary endpoints included a 12-week pCR rate and metastasis-free survival (MFS). Overall, 71% of participants achieved 2-year BIDFS, with 78% experiencing MFS. The pCR rate was impressive at 80% at 12 weeks, confirmed by cystoscopy, cytology, and biopsies.

Although longer follow-up is needed, this trial demonstrates a feasible treatment option for patients seeking to spare the bladder without compromising prognosis. The integration of chemoradiation as a therapeutic strategy is not established in all clinical centres. The experts suggest the treatment should be discussed depending on the patient’s condition. Both radiotherapy and chemotherapy require patient support and thorough information provided by both the radiologist and the surgeon.

In the presented trial, salvage cystectomies were performed in patients who experienced relapse. The experts discuss whether previous radiotherapy impacts surgery, potentially making it more challenging to remove the bladder. However, recent data show no reported complications that impact salvage surgery. Overall, this trial demonstrates that chemoradiation is a viable option, but its integration into practice poses challenges.