Oncology Late Recurrence and Progression in Non-muscle–invasive Bladder Cancers After 5-year Tumor-free Periods Kazuhiro Matsumoto, Eiji Kikuchi, Yutaka Horiguchi, Nobuyuki Tanaka, Akira Miyajima, Ken Nakagawa, Jun Nakashima, and Mototsugu Oya OBJECTIVES To evaluate the recurrence and progression in patients with non-muscle–invasive bladder tumors who remained tumor-free for at least 5 years, which should assist in the development of schedules of their follow-up evaluations. Non-muscle–invasive bladder tumors that recur or progress at a late time point are not rare. METHODS Between 1985 and 2002, 814 cases diagnosed with non-muscle–invasive bladder cancer were treated with transurethral resection. Of these 814 cases, 262 patients with no tumor recurrence for more than 5 years were included in the study. The median follow-up interval was 10.0 years. RESULTS During the follow-up period, 39 tumors (14.9%) showed tumor recurrence. The 5- and 10-year recurrence-free survival rates were 81.6% and 76.0%, respectively. There was no significant difference in tumor recurrence among the low-, intermediate-, and high-risk groups based on the current clinical guideline. Only the use of intravesical mitomycin C was determined to be a significant unfavorable risk factor for late recurrence. Five patients (1.9%) experienced stage progression, 3 of whom did not have metastases at the time of diagnosis of the progression but died because of bladder cancer disease. CONCLUSIONS After a 5-year tumor-free period, even in the low-risk group, recurrence occurred at a late time point to a degree that was the same as that for the intermediate- and high-risk groups. Finally, some of the high-risk patients experienced late progression with a high degree of malignant behavior, suggesting longer follow-up is needed for each patient. UROLOGY 75: 1385–1391, 2010. © 2010 Elsevier Inc. T ransurethral bladder tumor resection (TUR-BT), intravesical therapy, and frequent follow-up eval- uations for non-muscle–invasive bladder cancer are successful at reducing the number of tumor recur- rences and at maintaining most bladders free from stage progression. However, some patients with risk factors, such as grade 3 (G3), lamina propria infiltration, multi- plicity, a large tumor, and concomitant carcinoma in situ (CIS) are considered to have a lifelong frequency of multiple recurrences and a probability of stage progres- sion. 1-7 These results were obtained from data based on a large number of patients but were examined with median follow-up periods of less than 5 years. Early phase recur- rence or progression could be predicted correctly with their data, but they are insufficient to make an accurate estimate of the long-term course of non-muscle–invasive bladder cancer because of the short follow-up in their current analyses. Long-term follow-up data would pro- vide details of the exact outcome of late recurrence and progression in non-muscle–invasive bladder cancer. The recommended follow-up schedules proposed by the published guidelines vary, especially after 5-year tu- mor-free periods. 8-11 Fujii et al 12 pointed out that tumor recurrence and stage progression continue to occur in patients with superficial bladder cancer who remained tumor-free for more than 4 years after initial treatment. Meanwhile, Leblanc 13 reported that even in Ta G1 tu- mors a significant number of recurrences (14%) were observed more than 5 years after the first tumor. In contrast, Haukaas et al 14 stated that routine cystoscopy can possibly be discontinued in patients with low-grade, low-stage disease in the absence of recurrences during follow-up. Mariappan et al 15 also proposed that patients with Ta G1 tumors could be discharged with a 5-year tumor-free period on the basis of their long-term fol- low-up data. In this study, we reviewed 262 patients with diagnosed non-muscle–invasive bladder cancer who remained tu- mor-free for at least 5 years, to analyze their tumor recurrence and stage progression at a late time point. From the Department of Urology, Keio University School of Medicine, Tokyo, Japan; and Department of Urology, Tokyo Medical University, Tokyo, Japan Reprint requests: Eiji Kikuchi, M.D., Department of Urology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: eiji-k@kb3.so, http://net.ne.jp Submitted: March 8, 2009, accepted (with revisions): September 25, 2009 © 2010 Elsevier Inc. 0090-4295/10/$34.00 1385 All Rights Reserved doi:10.1016/j.urology.2009.09.088