Introduction & Objectives
The majority of patients with non-metastatic (M0) muscle-invasive bladder cancer (MIBC) are treated with neo-adjuvant chemotherapy followed by radical cystectomy (RC) and extended lymph node dissection. Despite this aggressive treatment the outcome is poor and ultimately 30% of the patients with ≥ pathological (p)T3 tumors develop a pelvic recurrence, which is rarely salvageable and is often associated with debilitating sequels. In the past, adjuvant external beam radiotherapy (EBRT) has shown to increase disease free survival, but excessive toxicity hampered enthusiasm for further implementation. In this phase 2 trial the place of adjuvant EBRT after RC for high-risk MIBC is re-investigated.

Materials & methods
In this Belgian multicentric prospective phase 2 trial, seventy-two patients were included and received treatment. Eligible patients were patients with MIBC, treated with RC and presenting with ≥1 of the following characteristics: pT3 stage + presence of lymphovascular invasion on pathological examination, pT4 stage, <10 lymph nodes removed, positive lymph nodes, positive surgical margins. Prior to EBRT, a post-operative 18F-FDG-PET-CT was performed to rule out distant metastases. A median dose of 50 Gy in 25 fractions was administered, using Volumetric-Modulated Arc Therapy (VMAT), to the pelvic lymph node regions with inclusion of the cystectomy bed in case of a positive surgical margin. A simultaneous integrated boost up to 70 Gy was delivered to PET-CT positive lymph nodes. The primary endpoint was acute grade ≥3 gastro-intestinal (GI) toxicity and in case of a neobladder reconstruction grade 4 urinary toxicity, within 12 weeks after EBRT. Secondary endpoints were late toxicity, local control, disease free survival and overall survival (OS). Toxicity was scored using the Radiation Therapy Oncology Group (RTOG) criteria and the Common Terminology Criteria for Adverse Events (CTCEA) v4.0.

Results
The median follow up was 15 months (1-72 months). Five (7%) patients had acute grade ≥3 GI toxicity. The 2-year probability of developing grade ≥3 and grade ≥2 GI toxicity was 18% and 79%, respectively. Of the seventeen neobladder patients 18% and 11% reported acute and late grade 2 urinary toxicity, respectively. Grade ≥3 urinary toxicity was not reported. The 2-year local recurrence-free survival and clinical relapse-free survival (CRFS) rates were 88% ±4% and 44% ±7, respectively. The mean CRFS time was 31 months (95% CI: 22-39 months). The 2-year OS rate was 52% ±7%, with a mean OS time of 39 months (95% CI: 31-48 months).

Conclusions
Using newer techniques such as VMAT, toxicity after adjuvant EBRT is acceptable. Preliminary survival data are encouraging and underline the importance of further evaluating the place of adjuvant EBRT in patients with high-risk and poor prognostic MIBC characteristics.

Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer: results of a phase II trial

For 2021, our focus remains: turning new data into your daily practice. The programme will consist of state-of-the-art lectures, case discussions and panel debates. Our faculty is a group of international & multidisciplinary experts.

We will take you on our journey to Ghent and beyond. Prior the congress, we send out case challenges, where you can compare your opinion with peers & experts. These cases will be part of the Global Congresses on Prostate & Bladder Cancer programme during the congress days (12 & 13 October for PROSCA and 14 & 15 October for BLADDR). After these days, you will be updated on prostate & bladder cancer management.