Resect or Preserve? Comparing treatment strategies in clinically node positive bladder cancer

Abstract

Purpose or Objective Worldwide there is wide variation in the management of patients with clinically node positive non-metastatic (cN+M0) bladder cancer. There is a paucity of high-quality evidence to guide practice. In many European centres, primary management of fit patients is radical surgery often preceded by platinum-based chemotherapy. In the UK in contrast, radical radiotherapy (RT) – a bladder-preserving treatment - is also offered as an alternative treatment to surgery. To aid clinician and patient decision making, an international multi-centre retrospective analysis was undertaken to assess clinical outcomes for cN+M0 bladder cancer receiving radical treatment. Materials and Methods Data on an international cohort of patients receiving surgery from 2007-2020 for cN+M0 bladder cancer was collated by sending data collection forms to a number of participating European Medical Centres in France, Italy, the Netherlands and Russia. Data was collected on a second cohort of cN+M0 bladder patients diagnosed at a large tertiary cancer centre in the UK from 2013-2020. Data was collected on treatment received, clinical outcomes and patient and tumour factors. Overall survival (OS) was calculated using date of TURBT as t=0. Kaplan-Meier curves for OS were produced for 3 cohorts ‘International’ patients receiving surgery, patients at the UK centre receiving surgery and UK patients receiving RT. Univariate and multivariate analyses were performed on the combined cohort to test for an association between nodal status, T stage, age, receipt of neoadjuvant chemotherapy (NAC) and OS. Results 245/369 patients with cN+M0 bladder cancer in the International cohort had OS data for comparison. At the UK centre, 52 patients received radical intent treatment with either surgery (n=18) or RT (n=34). OS was compared between the 3 cohorts (Figure 1). Median OS was 3.84 (2.28-NA), 1.85(1.05-NA) and 1.93(1.62-NA) years for the International, UK Surgery and RT groups respectively however a Log rank test showed no overall survival difference between the 3 cohorts (χ2=3.2, 2 df, p=0.2). In a univariable analysis OS positively associated with age <70 (HR 0.70 (0.49-0.98) p=0.04) and receiving NAC (HR 0.44 (0.31-0.62) p=0.28) and negatively associated with T stage 3 or 4 (HR 1.67 (1.14-2.44) p=0.01). Nodal stage (N1 vs N2/3) and Cohort (International vs UK) showed no statistically significant association with OS. Only NAC retained a significant association with OS within a multivariate analysis. Conclusion Our retrospective data does not find a significant difference in OS between cohorts receiving radiotherapy and surgery. Limitations in our data are the risk of confounders when comparing retrospective cohorts and the smaller number of RT patients with follow up beyond 3 years. Given the known reduced comorbidities and no operative risk with radiotherapy the data supports a greater use of radiotherapy in this cohort. Patients across Europe with cN+M0 bladder cancer should be offered both surgery and radiotherapy as treatment options.