Clinical question: Does one immediate intravesical gemcitabine instillation after TURBT reduce recurrence in suspected low-grade NMIBC?
Design: Randomized phase III trial; 406 eligible patients; immediate gemcitabine versus saline after TURBT. Median follow-up 4.0 years.
4-year recurrence: 67/201 (35%) gemcitabine vs 91/205 (47%) saline; HR 0.66 (95% CI 0.48–0.90), P<.001.
Absolute reduction 12 percentage points; NNT ≈ 9 at 4 years.
Recurrence: 34/102 (34%) gemcitabine vs 59/113 (54%) saline; HR 0.53 (95% CI 0.35–0.81), P=.001. Absolute reduction 20 points; NNT = 5 at 4 years.
Muscle invasion: 5/201 vs 10/205, HR 0.51 (0.17–1.49), P=.11. Death: 17/201 vs 25/205, HR 0.68 (0.37–1.27), P=.12. No grade 4 or 5 adverse events and no significant differences in grade ≤3 adverse events.
Patients with suspected low-grade NMIBC were randomized immediately after TURBT. The primary analysis used time to recurrence in the intention-to-treat population; the protocol-specified target population was those confirmed to have low-grade NMIBC and who received instillation.
This is an unusually simple intervention with a meaningful absolute effect: one postoperative instillation prevented approximately one recurrence for every 9 patients treated in the full eligible population and every 5 in the confirmed low-grade population. The benefit is recurrence reduction rather than demonstrated improvement in progression or survival.
SWOG S0337 supports immediate single-dose intravesical gemcitabine after TURBT for appropriately selected patients with suspected low-grade NMIBC, when perforation, extensive resection or other contraindications are absent. The benefit is prevention of recurrence; the trial did not demonstrate a significant reduction in muscle-invasive progression or mortality. The result should not be extrapolated to high-grade disease or used as a substitute for risk-adapted induction/maintenance therapy when indicated.
SWOG S0337 primary report, JAMA 2018 ↗ · EAU NMIBC guidance ↗