Timing of Adjuvant Mitomycin C Administration May Impact Bladder Cancer Recurrence Following Nephroureterectomy

Researchers at University of Florida Health are among the first investigators to evaluate the impact of the timing of intravesical mitomycin C administration on the rate of bladder tumor recurrence following radical nephroureterectomy for upper tract urothelial cancer.

Paul Crispen, M.D., an associate professor in the department of urology at UF, was an author of this groundbreaking study, published in Bladder Cancer in October 2018. According to Crispen, “These results may have practice-changing implications.”

About 80,000 people are diagnosed with urothelial cancer in the United States each year, and a majority of cases occur in the bladder. Upper tract urothelial cancer is rare, accounting for less than 10 percent of malignancies in the genitourinary tract. Radical nephroureterectomy with bladder cuff excision remains the standard surgical approach for high-risk patients and for lower-risk tumors that cannot be managed endoscopically. Unfortunately, bladder tumor recurrence is common, with rates up to 47 percent.

Crispen and colleagues retrospectively reviewed data for 51 adult patients who underwent radical nephroureterectomy for upper tract urothelial cancer, received intravesical mitomycin C during their perioperative course and had cystoscopic surveillance follow-up. The primary endpoint was bladder tumor recurrence rate within the first year after surgery.

The investigators categorized patients into two groups based on timing of intravesical mitomycin C administration:

• Patients who received mitomycin C intraoperatively or in the recovery room on the day of surgery
• Patients who received mitomycin C on the first day after surgery or later

The investigators found that earlier instillation of mitomycin C was associated with a decreased bladder tumor recurrence rate. The estimated probability of one-year recurrence was 16 percent for patients who received mitomycin C on the day of surgery and 33 percent for those receiving the drug on postoperative day one or later (log rank test P value = 0.09).

Crispen concludes, “While these results suggest the timing of intravesical chemotherapy administration may have an impact on the rate of bladder tumor recurrence, we need more evidence from prospective trials before we change current practice.”

Crispen and UF colleagues are currently enrolling patients in a Phase 2 trial at the University of Florida, the first prospective study of its kind to attempt to identify the importance of timing of mitomycin C administration relative to bladder tumor recurrence rate following radical nephroureterectomy. The ClinicalTrials.gov Identifier is NCT03658304. This study may provide answers to the question, “Does timing matter?”