Moyer Jacob A, Durant Adri M, Nguyen Mimi V, Mi Lanyu, Zganjar Andrew J, Lyon Timothy D, Shah Paras H, Boorjian Stephen A, Tyson Mark D
Graduate Research Education Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine and Science, Phoenix, Arizona.
Department of Urology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Scottsdale, Arizona.
J Urol. 2025 Jun 26:101097JU0000000000004658. doi: 10.1097/JU.0000000000004658.
Nadofaragene firadenovec-vncg is an FDA-approved therapy for bacille Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). Bladder spasms and medication leakage during intravesical instillation are common and can affect treatment efficacy. We evaluated the effect of rectal diazepam pretreatment on bladder spasm incidence, retention of instilled medication, and 3-month recurrence rates.
We retrospectively analyzed data from patients treated with nadofaragene firadenovec for BCG-unresponsive NMIBC at Mayo Clinic from November 28, 2023, through September 30, 2024. Patients were stratified by pretreatment with rectal diazepam (10 mg) vs other strategies. Outcomes included bladder spasms, retention of instilled medication, and 3-month recurrence rates.
Eighty-eight nadofaragene firadenovec instillations (45 patients) were evaluated. Rectal diazepam pretreatment was used for 25 instillations (28%) and associated with a 25% absolute risk reduction for nadofaragene firadenovec retention failure (4.0% vs 29% of instillations), as compared with other pretreatments (patient-level odds ratio, 0.22 [95% CI, 0.11-0.44]; < .001). In addition, we observed a 24% absolute reduction in bladder spasm incidence (32% vs 56% of instillations) in the rectal diazepam group (patient-level odds ratio, 0.32 [95% CI, 0.13-0.82]; = .02). Patients without medication leakage had a lower recurrence rate at 3 months (18% vs 38%), although this difference was not statistically significant ( = .3). One patient had fatigue attributable to rectal diazepam.
Rectal diazepam pretreatment may reduce bladder spasms and improve nadofaragene firadenovec retention during intravesical instillation, thereby enhancing efficacy. Rectal diazepam could improve patient comfort and treatment outcomes, thus warranting further investigation through larger, prospective studies.
纳多法基因菲拉地诺韦克 - vncg是一种经美国食品药品监督管理局（FDA）批准用于卡介苗（BCG）无反应性非肌肉浸润性膀胱癌（NMIBC）的治疗方法。膀胱内灌注期间膀胱痉挛和药物渗漏很常见，会影响治疗效果。我们评估了直肠给予地西泮预处理对膀胱痉挛发生率、灌注药物留存率以及3个月复发率的影响。
我们回顾性分析了2023年11月28日至2024年9月30日在梅奥诊所接受纳多法基因菲拉地诺韦克治疗BCG无反应性NMIBC患者的数据。患者按是否采用直肠给予地西泮（10毫克）预处理与其他策略进行分层。观察指标包括膀胱痉挛、灌注药物留存率以及3个月复发率。
共评估了88次纳多法基因菲拉地诺韦克灌注（45例患者）。25次灌注（28%）采用了直肠给予地西泮预处理，与其他预处理相比，纳多法基因菲拉地诺韦克留存失败的绝对风险降低了25%（灌注次数分别为4.0%和29%）（患者层面的优势比为0.22 [95%置信区间，0.11 - 0.44]；P <.001）。此外，我们观察到直肠给予地西泮组膀胱痉挛发生率绝对降低了24%（灌注次数分别为32%和56%）（患者层面的优势比为0.32 [95%置信区间，0.13 - 0.82]；P =.02）。无药物渗漏的患者3个月复发率较低（分别为18%和38%），尽管这一差异无统计学意义（P =.3）。有1例患者出现了与直肠给予地西泮相关的疲劳。
直肠给予地西泮预处理可能减少膀胱痉挛，提高膀胱内灌注期间纳多法基因菲拉地诺韦克的留存率，从而增强疗效。直肠给予地西泮可改善患者舒适度和治疗效果，因此有必要通过更大规模的前瞻性研究进一步探究。
