Value of a Marker Lesion in Non-Muscle-Invasive Bladder Cancer Patients Treated with Interleukin-2 Instillations: A Randomized Controlled Multicentre Trial

Abstract

Purpose: To compare the effect of intravesical interleukin-2 (IL-2) instillations with and without a marker lesion on time to recurrence (TTR) in non-muscle-invasive bladder cancer (NMIBC) patients. Methods: A prospective randomized, controlled trial was conducted. Patients with multiple non-muscle-invasive tumours were randomized for a complete or incomplete transurethral resection (TURBT), followed by 3 IL-2 instillations. The primary end point was TTR. Results: These are the results of an interim analysis, which was performed due to slow accrual after which the study was closed prematurely. Twenty-eight patients were randomized of which 17 were eligible on an intention-to-treat basis. Median TTR or last follow-up was 3 months (interquartile range [IQR] 3–10 months) for the complete and 4 months (IQR 3–8 months) for the incomplete TURBT group. The TTR between the 2 groups did not differ significantly (log-rank, p = 0.54). ­Conclusions: These data do not support the hypothesis that a marker lesion enhances the therapeutic effect of IL-2 instillations in patients with NMIBC.

Impact of Effective Intravesical Therapies on Quality of Life in Patients with Non-Muscle Invasive Bladder Cancer: A Systematic Review

“…The risk for performance bias (91%) and detection bias (100%) were exceptionally high due to lacking evidence of blinding procedures ( Figure 2 a,b). Blinding of patients but not the outcome data was performed in the study of Bosschieter et al [ 51 ] while Tan et al, 2019 [ 52 ] fulfilled all remaining components except blinding. The performance regarding selection bias was moderately poor, because 7 and 9 trials were rated high or unclear risk for random sequence generation and allocation concealment, respectively, including the 2 single-arm interventions [ 42 , 58 ] in which such procedures are completely lacked by default ( Figure 2 a).…”

“…The EORTC QLQ-C30 questionnaire was identified as the most frequently adopted validated instrument for measuring the global health status [ 43 , 44 , 45 , 48 , 50 , 53 , 54 , 55 , 57 , 58 ]. Three other studies measured health states of participants using the EQ-5D questionnaire [ 52 , 54 , 55 ], while general health was measured in two studies using the SF-36 heath survey [ 47 , 51 ] and SF-8 which is the abbreviated version of an original 36-item [ 57 ]. Within the context of generic QoL, these instruments also cover functioning and symptoms of physical, mental, and social health in certain extents: EORTC QLQ-C30: Contains 30 items to measure Global health status, functioning QoL (5 subscales), symptom QoL (8 subscales), and financial difficulties [ 59 ].…”

“…Numerous researchers measured the QoL more comprehensively using combination of a general QoL instrument with one or more other disease- or treatment-specific tools. The EORTC-BLS24 is a NMIBC-specific module of the QLQ-C30 for assessing health-related QoL that they were commonly coupled together and used in some studies [ 36 , 44 , 50 , 51 , 58 ]. Danielsson et al [ 49 ] developed their own 17-item questionnaire to measure the urinary bladder symptoms and burdens in NMIBC patients treated with BCG instillation.…”

“…Inclusive outcomes were reported in a small sampled RCT study was designed to compare the effects of intravesical IL-2 following incomplete TURBT with complete TURBT alone, although statistically insignificant positive and negative changes were observed in certain general- and NMIBC-specific QoL parameters in both arms [ 51 ].…”

“…In fact, the number of eligible studies included was still limited to cover existing intravesical modalities that are known to be effective. Regarding immunotherapy, aside from BCG, only a single study investigating the effects of interleukin-2 on QoL was identified which was insufficient to draw any conclusions [ 51 ], whilst many other agents such as interferon-alpha [ 19 , 20 ] and immune checkpoint inhibitors [ 72 ] were not addressed. Except for three identified studies on hyperthermia, other device-assisted modalities intravesical drug delivery such as EMDA [ 22 , 30 ] were completely lacking.…”