Intravesical instillation with mitomycin C and bacillus Calmette-Guérin in non-muscle-invasive bladder cancer (2026)

12. Patient quality of life (QoL)

12.1 Impact of intravesical instillations on patient reported outcomes (PROMs)

Future QoL is one of the most important questions for cancer patients. However, there are significant gaps in our knowledge and understanding of health-related quality of life (HRQoL) in patients undergoing treatment. Given the rapidly evolving landscape for treatment and management of NMIBC, understanding the burden of treatment and its impact on HRQoL is of paramount importance [150, 151].

Approximately 75% of bladder cancer patients have NMIBC at time of diagnosis, however, only 25% of studies conducted concerned HRQoL in NMIBC patients [152]. Nearly 60% of NMIBC patients have recurrent cancer leading to recommendation for routine repeated surveillance cystoscopies with resection, with or without intravesical chemotherapy or immunotherapy, which is standard of care in patients with intermediate or high-risk NMIBC [14]. Due to the unique burden of invasive surveillance, a better understanding of health status and HRQoL for NMIBC patients is urgently needed [153].

The European Organisation for Research and Treatment of Cancer (EORTC) defines HRQoL as:

“a multi-dimensional construct covering at least several key dimensions such as disease and treatment-related symptoms, as well as psychological and social functioning. HRQoL measures the (cancer) patient’s interpretation of the impact of a health condition on relevant aspects of their lives” [154].

In contrast, the World Health Organisation (WHO) defines QoL as:

“an individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns” [155].

In other words, HRQoL is the treatment-related, patient-perceived QoL (based on the EORTC definition) and QoL is based on daily life experiences. The term HRQoL was introduced to distinguish between general QoL and the current level of functioning as it is perceived by cancer patients.

NMIBC significantly affects a patient’s daily life for various reasons [156-158]. Emerging understanding of the significant impact of NMIBC cancer treatment on patient QoL improves the recognition of the relevance of PROMs within this patient-group [150, 151, 156].

The limited evidence base for PROMs in NMIBC is since there are limited RCTs; no preprocedural baseline assessments are available in many cases; and limited longitudinal data is available to evaluate the impact on patient HRQoL over time. Moreover, lack of adherence to guidelines [151], as well as high heterogeneity between studies, remains a challenge [156].

12.2 General HRQoL status and PROM questionnaires

HRQoL in patients living with and beyond bladder cancer is worse than that reported by the general population and those with other common cancers and seems to be independent of therapy received and stage [150]. Systematic reviews have found that NMIBC patients have a substantial symptom and functional burden that impacts HRQoL throughout the induction period of treatment. However, HRQoL returns to baseline level values by the end of the maintenance period of treatment [150, 158, 159].

Psychological distress and physical symptoms of patients are intense at the time of diagnosis; however, these symptoms are transient in patients receiving BCG therapy [156, 158, 160-162]. Measured by EORTC QLQ C30 & QLQ NMIBC 24, a general worsening in function domains such as physical, emotional and social function is seen from baseline during the induction phase but nearly reaches baseline level by the end of the maintenance phase [156]. For symptoms domain scores, the largest increase worsening of scores is seen for fatigue and urinary symptoms, followed by insomnia and nausea/vomiting [156, 158]. Erectile and sexual function are affected; however, scores also return to baseline level by end of maintenance after one year [156, 158].

12.3 Burden of symptoms and impact on HRQoL

The Nimbus trial tested whether a reduced number of standard doses of BCG instillations could improve HRQoL due to a possible reduction in toxicity or burden. However, reducing the instillation frequency does not improve HRQoL in patients with high-grade NMIBC [160].

Patients with NMIBC frequently exhibit urinary tract symptoms and fatigue. These symptoms can be partly responsible for the initial impairment of HRQoL, in addition to the cancer diagnosis [162].

A prospective RCT of the efficacy, safety and impact on HRQoL of a conservative maintenance strategy of BCG compared to an alternative strategy documented that there was no difference in function or symptom scores at fourteen-month follow-up [163].

Longitudinal data from a cohort study including 1,019 patients with a four-year follow-up time, showed that HRQoL in NMIBC patients was comparable with that of the general population after four years [162]. Improvements were noted in insomnia, social functioning and three NMIBC-specific symptoms, while minor deteriorations in appetite and diarrhoea lasted until 51 months. HRQoL in some domains was worse for high-grade NMIBC; high European Association of Urology (EAU) risk group; initial Bacillus Calmette-Guérin (BCG) treatment; being female; and being younger (< 65 yrs.) [162].

Another longitudinal study assessed the association between HRQoL and adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations in Dutch patients with NMIBC. Higher adherence to WCRF/AICR recommendations for BMI, physical activity and diet were linked to improved HRQoL [162, 164].

Overall, patients experience a high impact on HRQoL at the time of diagnosis but longitudinal data document that patients experience a gradual return to initial HRQoL status when undergoing frequent TURBT and instillation therapy. No evidence was found describing whether MMC or BCG is superior regarding impact on HRQoL.