Novel Treatment of Upper Tract Urothelial Carcinoma in Situ with Docetaxel in BCG Refractory Patients - Beyond the Abstract

Carcinoma in situ (CIS) of the urothelium within the bladder or upper tract is a highly progressive disease when left untreated. Topical therapy with Bacillus Calmette-Guérin (BCG) has been a mainstay of treatment both within the bladder and upper tracts. Patients who fail BCG therapy are left with limited options and are recommended for cystectomy or nephroureterectomy. Within the bladder, topical therapy with docetaxel has been shown to be efficacious in the setting of BCG-refractory bladder CIS. Therefore, we sought to determine efficacy for topical therapy with docetaxel in BCG-refractory patients with upper tract urothelial carcinoma in situ (UT-CIS).

One of the most challenging aspects of topical therapy for upper tract disease is adequate dwell time. Previous studies have assessed delivery methods such as reflux from a double-J ureteral stent, infusion with an open-ended ureteral catheter, and delivery via a percutaneous nephrostomy tube (PCN). Our preferred method of topical therapy delivery is via a 5-Fr open-ended ureteral catheter, which has been shown to provide the longest dwell time. Briefly, the ureteral catheter is placed in a retrograde fashion into the renal pelvis, and docetaxel is delivered over the course of 1 hour, followed by catheter removal and an additional dwell time of 1 hour by having the patient not void, if possible. Patients were given an induction course of six weekly instillations, followed by maintenance therapy of three weekly sessions at 3, 6, 12, 18, 24, and 36 months.

Patients selected for this study were those who had imperative indications to avoid surgery. For example, patients either had a solitary kidney, bilateral disease, or co-morbidities that precluded them from undergoing a major operation. In our cohort, there was a 60% initial complete response rate to docetaxel. This is in-line with docetaxel response rates to BCG-refractory bladder CIS. Yet, of particular interest are the three renal units which had no response to therapy. On final pathology, two renal units had significant pathologic upgrade and one renal unit had confirmed CIS. We hypothesize that patients that were upstaged likely did not have accurate initial staging. Indeed, these patients both had a previous cystectomy and urinary diversion, making accurate biopsy difficult. Further, the patient with confirmed CIS was the only patient which had topical therapy delivered via PCN. Though PCN delivery is efficacious, it is possible that there was not enough dwell time for maximal therapy.

Organ preserving therapy is of tantamount importance in this clinically challenging cohort. Our initial study showing the efficacy of docetaxel for BCG-refractory patients is promising, but more studies are needed to further define treatment specifics. Further, we noted that topical therapy with docetaxel was well tolerated, causing less irritative symptoms compared to BCG. Options for patients with BCG-refractory UT-CIS are extremely limited, and a course of topical docetaxel could prevent rendering patients anephric or with the difficult decision of choosing between palliative care and a high-risk surgery.

Written by: Andrew Katims, MD, MPH, Resident Physician, and Mantu Gupta, MD, Site Chair of Urology, Professor of Urology, Icahn School of Medicine at Mount Sinai, Department of Urology, New York, New York

Read the Abstract
email news signup