1. In this randomized controlled trial, time to recurrence was lower in patient with non-muscle-invasive urothelial cancer when treated with intravesical gemcitabine as compared to saline controls.
2. There was no difference in all-cause mortality between the two treatment groups.
Evidence Rating: 1 (Excellent)
Study Rundown: Non-muscle-invasive urothelial cancer is the most common form of bladder cancer; however, many recur following initial resection warranting close follow-up and ultimately repeat resection. Most commonly these cancers are removed via transurethral resection of bladder tumor (TURBT), and as of now, it is not widespread practice to instill postresection intravesical chemotherapy. In this randomized controlled trial, instilling postresection chemotherapy, specifically gemcitabine, was found to decrease tumor recurrence in non-muscle-invasive urothelial cancer when compared to saline treatment as a placebo. However, this significant decrease in tumor recurrence was not found in patients with high-grade non-muscle-invasive urothelial cancer or carcinoma in-situ, and there was no difference in all-cause mortality in patients who received gemcitabine as compared to placebo.
While this is one of the largest randomized studies to evaluate the effectiveness of postresection intravesical chemotherapy, results should be interpreted with caution, as they may not be generalizable beyond white males. Furthermore, information regarding tumor size at diagnosis or surgery was not collected and may contribute to subsequent tumor progression.
Relevant Reading: Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa–pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation?
In-Depth [randomized clinical trial]: SWOG SO337 was a multicenter, double-blind, randomized clinical trial that recruited 406 eligible patients with non-muscle-invasive urothelial cancer from January 23, 2008 to August 14, 2012. Participants were followed for four years post TURBT, and 201 were randomized to receive gemcitabine and 193 were randomized to receive saline with 190 and 168 undergoing a transurethral resection of bladder tumor, respectively. Patients were included if they had suspected low-grade papillary urothelial cancer based on cystoscopy performed for symptoms of bladder cancer, such as hematuria and excluded if they had a prior non-urothelial or muscle-invasive bladder cancer, if within 18 months of index TURBT, had any high-grade or more than 2 low-grade non-muscle invasive urothelial cancers, had intravesical therapy within the prior 6 months., previous pelvic radiotherapy, or prior treatment for a malignancy within 5 years except for non-melanoma skin cancer or non-muscle-invasive bladder urothelial cancer. In an intention-to-treat analysis, 67 patients in the gemcitabine group and 91 patients in the saline group experienced a recurrence within the 4-year median follow-up (HR 0.66; CI95 0.48 to 0.90). Among patients with low-grade disease, time to recurrence was significantly lower in the gemcitabine group as compared to the saline group (HR 0.53; CI95 0.35 to 0.81). In a post-hoc analysis, 86 patients were diagnosed with high-grade non-muscle-invasive urothelial cancer or carcinoma in-situ, and there was no difference in recurrence in those that received gemcitabine compared to those that received saline (HR, 0.84; CI95 0.45 to 1.60; p = 0.38). Overall, there was no difference in all-cause mortality between the two treatment groups (HR 0.68; CI95 0.37 to 1.27).
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