ESTRO 2024 Congress report

In Glasgow, during the last ESTRO congress, the secondary results were presented from the Belgian trial that evaluated the use of adjuvant radiotherapy after radical cystectomy and pelvic lymph nodes dissection +/- peri-operative chemotherapy. The rationale for the application of adjuvant radiotherapy is to reduce the risk of loco-regional relapse, which is a frequent (it occurs in 20-68% of cases), early (it occurs within 18 months of surgery), non-curable event that badly affects the quality of patients’ lives.

In this phase II multicentre trial, patients who were considered at high risk of relapse were defined as those with ≥one of the following characteristics: pT3 + lymphovascular invasion, pT4, pN+, <10 lymph nodes removed, or a positive surgical margin. Fluorodeoxyglucose positron emission tomography (FDG-PET) was performed to exclude patients with progressive disease. Then, six to 12 weeks after surgery, adjuvant volumetric modulated arc therapy (VMAT) (50Gy / 25 fractions) was delivered to pelvic lymph nodes and the cystectomy bed in case of positive surgical margins. The primary endpoint was toxicity. Local control was the secondary endpoint.

The characteristics of the 72 patients who were included in the trial are presented in Table 1. The median age of the patients was 70 years. Only 43% of the patients received neoadjuvant chemotherapy. Pathological analysis revealed a population at very high risk of relapse, with 80% diagnosed as pT3-4, 65% as pN+ and 19% with positive surgical margins.

Table 1: Patients’ characteristics

With a median follow-up of 52 months (interquartile range 37-60 months) for patients who were still alive, acute genito-urinary and gastrointestinal grade 3 toxicity was observed in 18% and 6% of these patients, respectively (Table 2).

Table 2: Acute toxicity data for patients

 

Encouraging efficacy results have been presented in this population, which has a very poor prognosis. Two-year loco-regional relapse-free survival was 78% ± 5%. Thus, five-year clinical relapse-free survival was 20% ± 5% with 33/46 recurrences observed outside the pelvis. Ten patients died. Overall survival was 46% ± 6% at years and 33% ± 6% at five years.

Whether or not the results from this phase II trial confirmed the safety of adjuvant radiotherapy in this setting, we can note that more than half the patients did not receive neo-adjuvant chemotherapy, and that the natural history of the disease is not only led by loco-regional relapse. Thus, the poor survival results are related to the very high-risk characteristics of the patients who were included in this trial, as they combined multiple adverse pathological factors. Data from randomised studies are awaited; these are the GETUG-AFU 30 (France) and the BART (India) trials, which comprise studies of patients with pathological high-risk disease randomised between surveillance and adjuvant radiation therapy, with a primary endpoint of loco-regional relapse-free survival.

Furthermore, in three randomised phase III trials, immunotherapy has demonstrated at least a disease-free survival benefit in the adjuvant setting, and this is now considered a standard of care by many physicians. Nevertheless, the population included in those trials was probably at lower risk than was that included in the Belgian study reported here; however, not all patients are eligible to receive immunotherapy due not only to their PDL1 status, but also to any comorbidities/contra-indications. The rate of grade 3 adverse events in adjuvant immunotherapy trials is high, varying between 16% and 48.4%. Radiotherapy remains an option to be considered and evaluated in a selected population.

The next steps in the adjuvant setting should be to combine both strategies (adjuvant radiotherapy and immunotherapy) in order to control the different risks of relapse (loco-regional and distant) through the use of the synergistic effect of the two treatments. Nevertheless, the feasibility and safety of such an approach has to be assessed and the best scheme (concomitant, sequential) must be determined. A tailored strategy is urgently needed for these patients, among whom a small subset will never relapse, another subset will present a quick distant spread, and another group might relapse only loco-regionally. Biomarkers are awaited in this setting and recent data from circulating tumour DNA are promising.

Dr Paul Sargos

Member of the ESTRO urology focus group

Department of Radiotherapy

Institut Bergonié

Bordeaux, France