Chemoablation in Urothelial Carcinoma: A Systematic Review and Future Perspectives - Beyond the Abstract

Our systematic review explores the available literature on the novel concept of chemoablation in the treatment of intracavitary urologic malignancies, specifically urothelial carcinoma of the upper tract and bladder. Additionally, we review current clinical trials and the potential direction of this novel treatment modality.

Urothelial malignancies can be challenging to treat given the high rates of recurrence and anatomic limitations. Surgical intervention has been the mainstay of treatment for urothelial carcinoma, ranging from endoscopic resection to organ extirpation. Despite advancements in surgical techniques and equipment, there remain limitations to the available technologies and a continuum of risks associated with surgical intervention. Thus, a subset of patients remain unsuitable or decline surgery. This dilemma has created a need for treatments that offer the advantage of the removal of diseased tissue while avoiding surgical risks. Chemoablation, which is the use of chemotherapeutic formulations to primarily ablate tumors, has recently emerged as one of these treatment options. This modality is distinctly different from adjuvant therapies, which are given in the absence of gross disease and are used to prevent disease recurrence or progression. 

In upper tract urothelial carcinoma (UTUC), endoscopic management has gained acceptance in guidelines and should be offered for most patients with low-grade disease given studies demonstrating equivalent survival. Unfortunately, due to limitations with endoscopic technology, difficulty with tissue sampling, anatomic variations limiting complete pyelocaliceal resection, and the field-effect of urothelial cancer, many patients with low-grade UTUC managed endoscopically will experience a recurrence. These patients are often treated with radical nephroureterectomy. The consequences of aggressive extirpation in low-grade disease do not come without consequence, as this population of patients is usually older, with comorbid conditions at higher perioperative risk and baseline renal function limitations. A newly approved novel chemoablative treatment using mitomycin (Jelmyto™) offers a new avenue for treating low-grade UTUC. This intracavity mitomycin for the pyelocaliceal system forms a gel in the upper tract that allows for prolonged contact of mitomycin against the urothelium to ablate upper tract tumors. This modality fills a needed treatment avenue in low-grade disease as it minimizes surgical risk, prioritizes renal function preservation, and can circumvent anatomic limitations encountered with endoscopic resection.

In the bladder, multiple chemoablative agents are currently being investigated for the management of nonmuscle-invasive bladder cancer. The interest in this form of treatment has been sparked by the proven clinical efficacy of many adjuvant therapies in ablating bladder tumors. To date, there are no approved ablative therapies for bladder cancer however clinical trials are ongoing. We expect that novel formulations of chemotherapeutics will improve the armamentarium available to urologists in the future.

While numerous chemoablative agents have shown preliminary evidence of efficacy and safety, the majority of available research is limited due to small patient cohorts, varying follow-up, and no standardized methodology to assess complete responses. Therefore, to date, it has not been widely adopted in treating urothelial carcinoma. We expect that this will change, as more studies investigating the efficacy of such agents are completed.

Written by: Muhannad Alsyouf, MD, Fellow of Urology, and Brian Hu, MD, Loma Linda University Health, Loma Linda University Medical Center, Loma Linda, California

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