Original Title: Evalueringsrapport vedrørende HAL-vejledt transurethral resektion af blæretumorer hos voksne patienter med mistanke om ikke-muskelinvasiv blærekræft

Authors' objectives: Transurethral resection of bladder tumor (TUR-BT) is the standard treatment for non-muscle-invasive bladder cancer (NMIBC) in Denmark. TUR-BT can be guided using various health technologies, including white light, narrow-band imaging (NBI), and blue light cystoscopy; in the present evaluation specifically hexaminolevulinate hydrochloride (HAL). HAL-guided TUR-BT may enable the detection of more tumors than its comparators, including carcinoma in situ, which can lead to a more complete resection. Ultimately, this may reduce the risk of recurrence and improve disease-free survival for patients. This applicant-initiated evaluation reviews the current evidence on the use of HAL-guided TUR-BT compared to NBI-guided TUR-BT for adult patients (≥18 years) with suspected non-muscle-invasive bladder cancer. The evaluation includes four areas of interest: Clinical effectiveness and safety, the Patient perspective, Organizational implications, and Health Economics. The Danish Healthcare Quality Institute based their recommendation on the use of HAL-guided TUR-BT on the findings in the evaluation report.

Authors' results and conclusions: Clinical effect and safety: The clinical effectiveness and safety of HAL-guided TUR-BT is evaluated based on a systematic review of the scientific literature. No studies were found that directly compare HAL-guided and NBI-guided TUR-BT in relation to the outcomes predefined by the expert committee. Therefore, HAL-guided TUR-BT is compared with white light cystoscopy (WLC). For the effect measure “recurrence rate” an indirect comparison using network meta-analysis (NMA) was conducted. HAL-guided TUR-BT may lead to clinically relevant reductions in the risk of disease progression (GRADE: Low) and bladder cancer recurrence (GRADE: Very Low) compared to WLC. In contrast, a meta-analysis of studies comparing NBI-guided TUR-BT with white light showed no statistically significant difference in the risk of recurrence. The applicant presented a NMA of HAL- and NBI-guided TUR-BT suggesting that HAL may cause a clinically relevant reduction in the recurrence risk compared to NBI. However, some evidence used in the NMA was unavailable, preventing formal confidence assessment per GRADE. No clinically relevant differences were found between HAL- or NBI-guided TUR-BT and WLC regarding health-related quality of life or complications (GRADE: Moderate). The expert committee concludes that HAL-guided TUR-BT may be superior to NBI-guided TUR-BT for recurrence rate, and possibly better than WLC for disease progression, but the evidence is highly uncertain, and several of the requested outcomes could not be addressed based on the existing literature. Patient perspective: There is a lack of reliable evidence to address the patients’ perspectives, as requested for the present evaluation. The expert committee assumes that most patients are likely to consider the discomfort associated with HAL instillation to be minor—especially if HAL proves effective in reducing recurrence and progression of bladder cancer over time. Organizational implications: HAL-guided TUR-BT was previously a well-established procedure in Denmark but has gradually been replaced by NBI in many hospitals. The expert committee considers that training staff in HAL instillation and performing HAL-guided TUR-BT does not pose a significant challenge to the use of HAL-guided TUR-BT. While there is a learning curve for surgeons to achieve optimal results using the health technology, this curve is comparable for both HAL- and NBI-guided TUR-BT. The main organizational challenges relate to the additional time nurses must spend instilling HAL before surgery. Another concern is the need for specialized equipment for HAL-guided TUR-BT, which must be partially and regularly replaced to maintain high procedural quality. These requirements introduce logistical and resource-related complexities. In contrast, NBI-guided TUR-BT does not face these issues, aside from the need for a permanently installed optical filter in the light source. In conclusion, while HAL-guided TUR-BT is technically feasible and staff training is manageable, the procedure involves greater organizational and practical challenges compared to NBI-guided TUR-BT. Health economics: The analysis includes a cost-utility analysis (CUA) and a budget impact analysis (BIA). The CUA indicates that HAL-guided TUR-BT is more costly than NBI-guided TUR-BT, with an additional cost of DKK 7,202 per patient. The increase in costs is mainly due to the cost of HAL and the extra staff time required for its instillation. HAL-guided TUR-BT is associated with a health benefit, corresponding to a gain of 0.095 QALY compared to NBI-guided TUR-BT. This result in an incremental cost-effectiveness ratio (ICER) of DKK 75,811 per QALY. However, the expert committee notes that the results of the CUA, including the estimated QALY gain, are subject to considerable uncertainty. It cannot be concluded with certainty that there is a true effect difference between the two technologies, although the trend favors HAL-guided TUR-BT. The uncertainty in the health economic results primarily reflects the uncertainty of the underlying clinical data. In line with the clinical effectiveness and safety assessment, HAL-guided TUR-BT may reduce recurrence risk and improve health-related quality of life, but the available data are highly uncertain. The BIA presents the estimated five-year budgetary impact for the Danish regions of a recommendation of increased use of HAL-guidance in TUR-BT from the Danish Healthcare Quality Institute. The expert committee notes that actual expenses will vary depending on local equipment replacement schedules and considers a gradual implementation of HAL-guided TUR-BT to be expected in the case of a potential recommendation of the health technology.

Project Status: Completed

URL for project: https://www.sundk.dk/media/ix3djcaz/anbefaling-hal-vejledt-tur-bt.pdf

Year Published: 2025

URL for published report: https://www.sundk.dk/media/ix3djcaz/anbefaling-hal-vejledt-tur-bt.pdf

English language abstract: There is no English language summary available

Publication Type: Not Assigned

Country: Denmark

Organisation Name: The Danish Health Technology Council

Contact Address: Niels Jernes Vej 6a, 9220 Aalborg