In the present study, 76 (45.8 %) of the 166 patients were diagnosed with UC of the UUT at the first examination. Although the detection rate of UC of the UUT was lower than in previous studies [5, 6], we consider that it is strongly influenced by the indication of diagnostic ureteroscopy at each institution. As aforementioned, we proceed directly to radical surgery without ureteroscopy in patients showing apparent imaging findings with a positive urinary cytology, and this would contribute to our lower detection rate. The incidence of urinary stones was low in our cohort, because patients requiring stone treatment were usually referred to our teaching hospitals.
At the initial diagnosis, UC of the UUT was not detected in surgical specimens in 3 patients (5.8 %, 3/52). The final pathology revealed dysplasia in one patient and the remaining two patients had neither carcinoma nor dysplasia. Of these three patients, one was diagnosed with a pelvic tumor due to positive washing cytology. This patient had concurrent bladder carcinoma, and contamination by carcinoma cells from bladder cancer would lead to a misdiagnosis. The remaining two patients were diagnosed by mucosal biopsy, which would suggest the difficulty of pathological diagnosis using small biopsy samples. Tsivian et al. reported a similar rate of misdiagnosis (not UC based on final pathologic findings), whereby it was 2.1 % (1/48) with routine ureteroscopic assessment [5]. Interestingly, they reported that the rate of misdiagnosis was 15.5 % (9/58) before routine ureteroscopic evaluation, which suggested improvement of the diagnostic accuracy due to ureteroscopy.
After the first ureteroscopy, follow-up data were available in 65 patients with a median of 41 months (range: 3–170 months), and UC of the UUT was detected on second ureteroscopy in 5 patients. Because one additional patient developed metastatic urothelial carcinoma detected by CT, UC of the UUT was detected in a total of 6 patients (6/65, 9.2 %) at a median of 43.5 months (range: 10–59 months) after the first ureteroscopy, which was an unexpectedly high detection rate. Regarding Case 2 in Table 2, because the interval between the first ureteroscopy and definitive diagnosis was relatively short (10 months), we considered that UC of the UUT carcinoma might be missed at the first examination. In the remaining 5 patients, because UC of the UUT was diagnosed after more than two years (range: 28–60 months), these carcinomas might be de novo development rather than being missed at the first examination. Cases 1, 3, and 4 had concurrent bladder cancer, and it is well-known that patients with bladder cancer are at risk of upper urinary tract recurrence. Picozzi et al. reported in their meta-analysis that the incidence of upper urinary tract recurrence after cystectomy ranged from 0.75 to 6.4 % [7]. However, interestingly, the laterality of the carcinoma was the same as that observed at the first examination in all 6 cases, although we could not clarify the precise mechanism. At present, we consider our observations to suggest that later cancer detection of UC of the UUT was not uncommon after the first examination, but this should be verified in another cohort.
Regarding the risk factors of later cancer detection, the univariate model identified episodes of gross hematuria (p = 0.0048) and abnormal cytological findings (p = 0.0335) during the follow-up and a male sex (p = 0.0316) as adverse risk factors. Regarding the sex difference, previous epidemiologic studies revealed conflicting observations of a male [8–10] or a female [11] predominance in the incidence of UC of the UUT. Alternatively, a difference in accessibility to the upper urinary tract between males and females, due to differences in the urethral length, may influence the outcome. In the present study, the hazard ratio of males to females could not be calculated due to the absence of later cancer detection in the female cohort. When adjusting for episodes of gross hematuria and abnormal cytological findings in the multivariate model, episodes of gross hematuria remained significant (hazard ratio: 7.84, 95 % confidence interval: 1.32-61.7, p = 0.0239).
This study had several limitations, including its retrospective design, small sample size, and variations in ureteroscopies, as well as each surgeon’s experience and proficiency during the study periods. In addition, we could not follow all patients after the first examination and did not have a uniform follow-up protocol, such as an indication for repeat ureteroscopy. Nevertheless, we consider that several important findings were yielded by the present study.
