Seeding and implantation are major mechanisms of intravesical recurrence (IVR) following the radical nephroureterectomy (RNU) of upper tract urothelial carcinoma (UTUC). We herein hypothesized that bladder biopsies (BB) may increase the IVR risk by promoting implantation in injured bladder mucosa.
This retrospective study included 172 patients with UTUC with no history of bladder UC who underwent RNU between January 2010 and December 2024 at two institutions. The primary endpoint was the association between BB and IVR-free survival (IVRFS) after RNU. A directed acyclic graph (DAG) was generated to identify potential confounders and guide multivariable analysis, and sensitivity analyses using propensity score matching were performed.
Eighteen (10%) patients underwent BB prior to RNU due to a positive voided urine cytology finding and/or the presence of erythematous mucosa. Patients receiving BB had significantly shorter IVRFS than those without BB (3-year IVRFS rate: 14% vs. 69%; P < .001). On both DAG-guided and stepwise multivariable models, BB was independently associated with an increased IVR risk (hazard ratio: 2.55 and 4.00, respectively; both P < .005). In the propensity score-matched cohort, BB was also associated with a shorter IVRFS. Notably, IVR developed at the BB sites in 60% of the cases of IVR following BB.
BB is likely to increase the IVR risk in patients undergoing RNU for UTUC by promoting tumor cell implantation. Avoiding BB may be prudent unless both urine cytology and cystoscopic findings are highly suspicious for bladder carcinoma.
Japanese journal of clinical oncology. 2026 May 12 [Epub ahead of print]
Tomonori Kanagawa, Ichiro Yonese, Takehiro Nakamura, Mai Shimizu, Rie Tanaka, Hajime Kido, Tsukasa Shinoda, Ken Sekiya, Takahiko Soma, Masahiro Toide, Masaya Ito, Ryoji Takazawa, Fumitaka Koga
Department of Urology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan., Department of Urology, Tokyo Metropolitan Ohtsuka Hospital, 2-8-1 Minami-Ohtsuka, Toshima-ku, Tokyo 170-8476, Japan.