INTRODUCTION AND OBJECTIVES

Low grade upper tract urothelial carcinoma (LG-UTUC) is currently treated by endoscopic resection when possible and by nephroureterctomy (NU) when tumor volume or location preclude conservative management. Endoscopic resection of UTUC, though increasingly common, is associated with high recurrence rates and the need for repetitive surgical interventions. There are currently no approved drugs for LG-UTUC. An improved approach to this population would provide effective tumor control, limit the need for repetitive surgical treatment and minimize the risk of subsequent NU. We report the initial results of chemoablation with a prolonged release formulation of mitomycin as primary therapy for LG-UTUC as an alternative to surgery.

METHODS

After approval by institutional review boards and obtaining informed consent, 33 patients with biopsy proven, unilateral LG-UTUC were enrolled in the OLYMPUS Trial. Patients were treated with 6 weekly instillations of UGN-101 (MITOGEL-TM), a prolonged release, reverse thermal gel formulation containing mitomycin. The gel was administered via retrograde catheter to a maximum volume of 15cc. Gel instillations were performed after careful measurement of renal pelvic volumes under fluoroscopic control. All patients had measurable tumor at the time of treatment initiation (minimum lesion size >0.5 cm). Thirty-eight percent of enrolled patients had tumors located in regions of the kidney not amenable to surgical resection. Four to six weeks following the last instillation, patients underwent a primary disease evaluation (PDE) including ureteroscopy of the treated system and wash cytology. A complete response was defined as negative ureteroscopic evaluation and negative wash cytology.

RESULTS

Of the 33 patients evaluated for this report, 28 have undergone PDE assessments. The complete response rate in the intent to treat (ITT) cohort is 57% (16/28). Five patients are still pending PDE results. Six patients have undergone 3-month follow-up and remain in complete response. Treatment-emergent adverse events included urinary tract infection, flank pain, and transient creatinine elevation with most reported as mild or moderate. All participating subjects will be followed for a minimum of 12 months following PDE to determine the durability of disease control.

CONCLUSIONS

These interim data support our previous observations that non-invasive, urothelial cancer of the upper tract can be ablated using a reverse thermal gelation technology potentially resulting in less surgical intervention and nephrectomies. This pivotal study continues to enroll patients, with top-line data expected later this year.