Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial

Abstract

Background: High-risk muscle-invasive bladder cancer (MIBC) has a poor prognosis. Old trials showed that external beam radiotherapy (EBRT) after radical cystectomy (RC) decreases the incidence of local recurrences but induces severe toxicity. Objective: To evaluate the toxicity and local control rate after adjuvant EBRT after RC delivered with volumetric arc radiotherapy. Design, setting, and participants: This is a multicentric phase 2 trial. From August 2014 till October 2020, we treated 72 high-risk MIBC patients with adjuvant EBRT after RC. High-risk MIBC is defined as pT3-MIBC ± lymphovascular invasion, fewer than ten lymph nodes removed, pathological positive lymph nodes, or positive surgical margins. Intervention: Patients received 50 Gy in 25 fractions with intensity-modulated radiotherapy to the pelvic lymph nodes ± cystectomy bed. Outcome measurements and statistical analysis: The primary outcome is acute toxicity. We report on local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS), and bladder cancer-specific survival (BCSS). Results and limitations:The median follow-up is 18 mo. Forty-two patients (61%) developed acute grade 2 gastrointestinal (GI) toxicity. Four patients (6%) had acute grade 3 GI toxicity. One patient had grade 5 diarrhea and vomiting due to obstruction at 1 mo. Twoyear probabilities of developing grade 3 and 2 GI toxicity were 17% and 76%, respectively. Urinary toxicity, assessed in 17 patients with a neobladder, was acceptable with acute grade 2 and 3 urinary toxicity reported in 53% (N = 9) and 18% (N = 3) of the patients, respectively. The 2-yr LRFR is 83% ± 5% and the 2-yr CRFS rate is 43% with a

Dosimetric comparison between intensity modulated radiotherapy and three-dimensional conformal radiotherapy in adjuvant setting after radical cystectomy in high-risk urothelial bladder cancer

“…Simultaneous integrated boost (SIB) of up to 70 Gy was delivered to suspicious lymph nodes detected in 18F-FDG-PET-CT. The study suggested that adjuvant RT resulted in good LC and acceptable toxicity (Fonteyne et al, 2021).…”

International Consensus Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy: Update From an IBIS Workgroup

“…Between August 2014 and October 2020, 72 patients with MIBC were treated with ART after RC within a Belgian prospective phase 2 trial. 7 Within this trial, all patients received elective pelvic nodal irradiation using intensity modulated arc therapy. The lymph node areas located along the common, internal and external iliac artery, obturator fossa, and presacral were delineated.…”

“…5 These trials suggested that ART is safe and effective. 6,7 To guide the contouring of the clinical target volume (CTV) for ART in these high-risk MIBC patients after RC, in 2016, international consensus CTV (CTV-IC-2016) guidelines were published by Baumann et al 8 After external validation, Reddy et al 9 proposed an optimized CTV (CTV-OPT). The aim of this study was to develop updated international consensus CTV guidelines by evaluating the current contouring practice that makes use of existing guidelines and the locoregional ART results.…”

Insights on recent innovations in bladder cancer immunotherapy

“…For patients with muscle‐invasive bladder cancer who are ineligible for cisplatin chemotherapy, upfront radical cystectomy is the preferred treatment paradigm 12 . Adjuvant chemotherapy (if not treated with neoadjuvant chemotherapy before) or the immunotherapeutic agent nivolumab (anti‐ T‐cell PD‐1 receptor), which is often prescribed for patients with high risk for cancer recurrence after cystectomy 13,14 …”

“…12 Adjuvant chemotherapy (if not treated with neoadjuvant chemotherapy before) or the immunotherapeutic agent nivolumab (anti-T-cell PD-1 receptor), which is often prescribed for patients with high risk for cancer recurrence after cystectomy. 13,14 Patients with inoperable or metastatic BC are usually treated with palliative, multiagent platinum-based chemotherapy. 9 If there is no cancer progression after chemotherapy, avelumab (anti-PDL-1 on tumor cells) maintenance therapy is the standard of care.…”