The OLYMPUS Trial for Patients With Low-Grade UTUC

Surena F. Matin, MD, The University of Texas MD Anderson Cancer Center, and David Ambinder, MD, Urology Resident, New York Medical College/Westchester Medical Center, contextualize the OLYMPUS trial as having practice-changing potential for patients with low-grade, low-volume UTUC.

Dr. Ambinder: Could you provide a summary of the findings from the OLYMPUS trial?

Dr. Matin: The OLYMPUS trial focused on a unique formulation of mitomycin combined with a hydrogel. The hydrogel has distinct properties, transitioning from a viscous liquid to a jello-like consistency when heated to body temperature. This allowed for a slow release of mitomycin, which dissolved in urine at a consistent rate.

Initially, we obtained compassionate use approval from the FDA for each patient, as there was no standard treatment available other than lymphadenectomy. The FDA acknowledged the potential for kidney preservation and set a low bar for response rate (18-25%) without defined adverse event limits. I was impressed by the FDA’s knowledge and flexibility during our interactions.

The study enrolled patients with biopsy-proven low-grade upper tract cancer, restricting tumors to 1.5 centimeters or smaller. Laser ablation of ureteral tumors was necessary before treatment. The patients received the drug once a week for 6 weeks through retrograde delivery. Six weeks later, a ureteroscopy was conducted to assess complete response.

The study demonstrated a 59% complete response rate among the 80 patients involved. Follow-up data indicated durability in approximately 56% of those who achieved a complete response over a year. The trial established this treatment as a new standard for low-grade, low-volume upper tract cancer. However, the study revealed a high adverse event profile, with approximately 35-40% of patients experiencing ureteral narrowing or stenosis.

In hindsight, we learned that this narrowing is likely related to repeated mechanical trauma combined with the caustic effects of mitomycin. Initially, edema is observed, possibly similar to eosinophilic reactions seen in the bladder. If this occurs, the recommended course of action is to place the patient on a drug holiday for 2 to 3 weeks and consider steroid treatment to address the inflammatory aspect. This approach mitigates the risk of permanent strictures, as some patients who developed permanent strictures required definitive management later.

These are the lessons we have learned since the trial’s completion.

Dr. Ambinder: Do you think a percutaneous or antegrade approach can minimize the risk of strictures?

Dr. Matin: There is promise in utilizing these approaches. Initially, I was hesitant but learned that other leaders in the field had started using them. After consulting with Kate Murray and Jen Linehan, who were involved in the trial, I followed their lead and implemented a similar process. In the past few years, this has become my preferred method, and I am now the highest-volume user in the United States due to the number of patients I treat.

We do not observe strictures or narrowing with this approach. Although I still use antegrade fluoroscopy for each patient, I am considering discontinuing it unless there are specific issues like hematuria. It simplifies the process significantly. However, patients do need to live with a nephrostomy tube for approximately 7 weeks. We administer weekly treatments through the tube once we determine the appropriate drug volume based on the renal pelvis size. It has been easier for patients, particularly considering the quick office visits compared to a procedure.

Dr. Ambinder: This approach seems beneficial for both patients and your practice.

Dr. Matin: We believe so. However, we need more data to determine if the efficacy is equivalent and to solidify safety conclusions. There is a retrospective publication available, and more studies should be forthcoming. Moreover, there is no scientific basis for the 6-week treatment frequency. For frailer patients or those who need a family member to accompany them, coming in every 2 to 3 weeks could be an alternative. Low-grade tumors generally have a low proliferative rate, so modifying the protocol slightly should not negatively impact patients, although more data would be helpful.

View their other comments on Staging and Therapeutic Considerations of Lymphadenectomy for UTUC and the Right Patents and Optimal Techniques for Kidney Sparing in UTUC.