Clinical practice guideline amendments detail novel urinary biomarkers and agents that may improve Bacillus Calmette-Guerin efficacy in the management of non-muscle invasive bladder cancer.
Amended evidence-based guidelines from the American Urological Association (AUA), made in collaboration with the Society of Urologic Oncology (SUO), aim to improve clinician’s ability to assess and manage non-muscle invasive bladder cancer (NMIBC).
According to findings published in the Journal of Urology, practices should consider administering treatment with a restaging transurethral resection of bladder tumor (TURBT) anywhere from 4 to 6 weeks following an initial TURBT if a patient has variant histology.1 Because variant histology was found to confer worse overall survival in a study from Iida et al,2 the guideline authors recommended that those with mixed histologic features should undergo aggressive treatment modalities in place of protocols that spare the bladder. Additionally, surgeons were recommended to consider offering early cystectomy to patients due to a high rate of upstaging related to variant histology and the presence of lymphovascular invasion.
The guidelines also supported using biomarkers for evaluating intravesical Bacillus Calmette-Guerin (BCG) and adjudicating equivocal cytology among patients with NMIBC. For example, the authors described the UroVysion® fluorescence in situ hybridization (FISH) as a tool that may be predictive of responses to intravesical BCG treatment. Although data suggested that UroVysion may yield less diagnostic accuracy compared with urine cytology, the authors stated that the former may nevertheless help distinguish between patients with disease recurrence and those without.
The authors of the guideline offered a moderate recommendation that a single postoperative instillation of intravesical chemotherapy within 24 hours of TURBT should be considered if a patient is suspected to have low- or intermediate-risk bladder cancer. Additionally, those with suspected perforation or extensive resection may not be suitable to undergo treatment with postoperative chemotherapy. Clinicians may also make a conditional recommendation for clinical trial enrollment for those with persistent or recurrent high-grade NMIBC within 1 year of completing BCG therapy who are not eligible to receive subsequent cystectomy; pembrolizumab (Keytruda) may also be offered to patients with carcinoma in-situ within 12 months of completing BCG therapy.
A moderate recommendation was also given in support of radical cystectomy for a patient with high-risk persistent or recurrent disease within 12 months of BCG induction or maintenance therapy. The authors also moderately supported blue cystoscopy during TURBT for increasing detection and potentially reducing recurrence. Findings from the PHOTO trial published in NEJM Evidence highlighted no differences in the incidence of disease progression between patients with intermediate- and high-risk NMIBC who received white light or blue light resection (HR, 1.41; 95% CI, 0.67-2.96).3
The authors offered a conditional recommendation for narrow-band imaging as a readily available tool for increasing detection in those with NMIBC. Although no evidence suggested that this technology may reduce the possibility of recurrence, it did not appear to heighten recurrence risk in patients.
“One of the fastest growing spaces in urologic oncology is in the treatment of [NMIBC],” Jeffrey M. Holzbeierlein, MD, a physician in chief at The University of Kansas Cancer Center, a William L. Valk Endowed professor at the University of Kansas Medical Center, president at SUO, and chair for the guideline amendment, said in a news release on the publication of the revised guidelines.4 “The updated guideline incorporates the latest data and outcomes regarding a number of new treatments and is intended to help navigate one of the most complex conditions we treat as urologists.”
The authors also stated that the future directions of novel urinary biomarkers held promise, citing the CX Bladder platform as an example of how advances can be made in the sensitivity of detecting high-grade NMIBC. Additionally, nadofaragene firadenovec-vncg (Adstiladrin) was highlighted as a novel agent for improving BCG efficacy or managing BCG failure. Nadofaragene received FDA approval as a treatment for those with NMBIC in December 2022, specifically those with high-risk BCG–unresponsive disease with carcinoma in-situ with or without papillary tumors.5