Association of patient-reported pain with survival in bladder cancer: a post-hoc analysis of the iBLAD trial

Abstract

This post-hoc analysis of the iBLAD trial investigates the association of patient-reported symptoms with survival in bladder cancer (BC) patients during and after oncological treatment.

Patient-reported outcomes (PRO) are increasingly being used in clinical and research settings to assess self-reported symptoms during oncological treatment [Citation1,Citation2]. The FDA and EMA recommend the inclusion of PROs in all clinical research studies [Citation3,Citation4]. Furthermore, the active use of PROs compared to standard care for symptom-handling during cancer therapy has been shown to improve QoL and even survival [Citation5,Citation6]. More studies have demonstrated how PROs can be used as a complementary tool to assess, monitor and manage symptoms during oncological treatment [Citation7–10].

Several studies have also shown that patient-reported outcome measures can serve as a prognostic tool [Citation6,Citation9,Citation11–13]. PRO measures associated with decreased survival include fatigue, global health, quality of life, pain, loss of appetite and physical function [Citation6,Citation9,Citation11,Citation13–15].

This study aims to evaluate the prognostic significance of patient self-reported symptom scores using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE, henceforth PRO) and secondly to identify symptoms associated with reduced survival in BC.

Materials and methods

The present study is a post-hoc analysis of PRO questionnaire responses in the intervention arm of a randomized clinical trial (NCT03584659) [Citation16,Citation17]. The data presented have not been previously published. Feasibility, pilot study, symptom, and item selection for iBLAD were performed in previous studies [Citation18–20]. The PRO questionnaire covered 16 symptoms (32 items) from the PRO-CTCAE library [Citation21]. Locally advanced disease was defined as patients with T2-TxNx disease, and metastatic disease was defined as patients with M1 disease. No patient had started treatment before randomization.

Treatment was carried out according to Danish national guidelines, which follow the European guidelines for BC [Citation22,Citation23]. Physicians and nurses at the treatment centers had access to PRO responses, which were checked at each patient visit, and further an alert algorithm, guided the patient on how to manage the given symptoms, either by symptom-specific self-management or by contacting the treating department (Figure S1). Standard clinical practice for symptom management was used when contacting the department, following local guidelines without a specific management algorithm. Each PRO question has five possible responses, ranging from no symptoms to high symptom burden (Tables S1 and S2).

Figure 1. Kaplan–Meier curve of baseline pain levels. Log-rank/ Mantel–Cox test is performed, p-value in graph.