|Year : 2021 | Volume
| Issue : 3 | Page : 98-103
Ureteroscopy for the diagnosis of upper tract urothelial cancer: The outcome in a series with 275 patients in correlation with the final histopathology
Yasser Osman1, Mohamed Mohamed Elawdy1, Diaa Eldin Taha2, Mohamed Abd El-Hamid3, Rasha Taha Abouelkheir4
1 Department of Urology, Urology and Nephrology Centre, Mansoura University, Egypt
2 Department of Urology, Faculty of Medicine, Kafrelsheikh University, Egypt
3 Department of Pathology, Urology and Nephrology Centre, Mansoura University, Egypt
4 Department of Radiology, Urology and Nephrology Centre, Mansoura University, Egypt
|Date of Submission||03-Feb-2021|
|Date of Decision||18-May-2021|
|Date of Acceptance||25-May-2021|
|Date of Web Publication||01-Sep-2021|
Mohamed Mohamed Elawdy
El Gomhoria street, Urology and Nephrology Center, Mansoura University, Mansoura
Source of Support: None, Conflict of Interest: None
Background: There is still an unresolved debate about whether ureteroscopy (URS) and biopsy are required as a routine for the diagnosis of upper tract urothelial cancer (UTUC) or if these procedures can be omitted in appropriately selected patients. We aimed to report the overall diagnostic accuracy of URS biopsy for ureteral tumors in concordance with the final histopathology. Materials and Methods: We conducted this retrospective study from 2000 to 2019. Data on URS biopsies for ureteral tumors which included pathological diagnosis, staging, and grading were collected. These data were then compared to the results of contrast-enhanced computed tomography (CT) and the final histopathological reports. Results: The data of 275 patients with a mean age of 59 ± 11 years were collected. Complete data regarding URS biopsies for ureteral tumors were available in 94 cases with an overall diagnostic accuracy in detecting malignancy of 93%. When matched to the final histopathology, the accuracy of URS biopsies increased as the tumor grade increased. Upgrading was noticed in 36% of the biopsies. Biopsy grade was an accurate predictor of stage. CT was performed in 270 cases with an overall accuracy of 96%. URS did not affect post-UTUC intravesical recurrence (P = 0.9) or overall survival (log rank = 0.08). Conclusion: URS biopsy for ureteral tumors was highly specific with fair predictive ability for tumor grade, and it could predict tumor stage. URS may not increase intravesical recurrence or affect overall survival. However, false-negative results were noted, which did not change the surgical plan when radical surgeries were decided based on CT.
Keywords: Nephroureterectomy, transitional cell carcinoma, upper tract urothelial carcinoma, ureteroscopy, urothelial cancer
|How to cite this article:|
Osman Y, Elawdy MM, Taha DE, El-Hamid MA, Abouelkheir RT. Ureteroscopy for the diagnosis of upper tract urothelial cancer: The outcome in a series with 275 patients in correlation with the final histopathology. J Cancer Res Pract 2021;8:98-103
|How to cite this URL:|
Osman Y, Elawdy MM, Taha DE, El-Hamid MA, Abouelkheir RT. Ureteroscopy for the diagnosis of upper tract urothelial cancer: The outcome in a series with 275 patients in correlation with the final histopathology. J Cancer Res Pract [serial online] 2021 [cited 2021 Dec 5];8:98-103. Available from: https://www.ejcrp.org/text.asp?2021/8/3/98/324922
| Introduction|| |
The diagnosis of upper tract urothelial carcinoma (UTUC) has traditionally been based on the presence of filling defects in intravenous urography and positive cytology. However, technical innovations in imaging studies and endoscopic equipment have led to improvements in the diagnostic accuracy of UTUC. With the advent of minimally invasive and renal sparing/preservation surgery, precise preoperative assessments of the stage, grade, multiplicity, and status of the entire urothelial collecting system are essential for a urologist to make sound clinical decisions.
Ureteroscopy (URS) is a well-documented diagnostic modality for UTUC, however, previous reports are limited by the number of patients.,, Furthermore, the necessity of performing URS as a diagnostic step in all patients with UTUC has not been addressed. Potretzke et al. suggested that URS can be omitted as part of the diagnostic work-up in appropriately selected patients, whereas Golan et al. considered this to be a crucial step in confirming UTUC and treatment planning. Furthermore, there is still an unresolved debate on whether URS increases intravesical recurrence and overall survival.,
The aim of this study was to report on the overall diagnostic accuracy of URS in a single cohort of patients with ureteral tumors, and the concordance of biopsy grade to the final histopathology, as well as how far the URS biopsy grade can predict tumor stage. Moreover, the impact of URS on intravesical recurrence and overall survival were recorded in a large series of patients treated at a single tertiary institute.
| Materials and Methods|| |
After institutional review board approval (UNC, 81C/ 2017) and obtaining the patient consent, we conducted this retrospective study by reviewing the hospital database of patients who were surgically treated for UTUC from January 2000 to December 2019. All personal demographic characteristics and documented details of preoperative assessments and operative procedures were collected, including routine laboratory investigations and radiological images of preoperative contrast-enhanced computed tomography (CT). Further data of UTUC patients who underwent preoperative URS for ureteric tumors were analyzed, and the results of ureteroscopic biopsies were compared to the results of final histopathological specimens. Biopsies for pelvicalyceal tumors were excluded to yield a homogenous sample.
In all patients and in separate sessions, patients were scheduled for cystoscopy, cytology, retrograde pyelography (RP), and URS. Any concomitant bladder tumors were resected. Upper urinary tract cytology was obtained by retrograde catheterization and flushing with 3–5 ml of saline solution before contrast administration. RP was then performed except in cases of large pelvicalyceal tumors that were confirmed by imaging, large obstructed ureteral tumors, or tumors protruding from the ureteral orifice.
Biopsies were obtained by URS using ureteroscopes of various sizes depending on the availability and historical development of the equipment. A flexible URS (Olympus, URF-V) 9.9F was used when available. Cup biopsy was performed in all patients using 3F cold cup biopsy forceps. The specimen was fixed in formalin and sent for pathological examination. Multiple samples were taken, and the results were drawn from the most representative ones.
The following data were excluded from URS biopsies: those with tiny growths that were treated by LASER ablation and fulguration, patients with hematuria with large pelvicalyceal tumors that were confirmed by imaging, inaccessible tumors for URS, and tumors that caused gross hydronephrosis with poorly functioning kidneys requiring nephrectomy. All data regarding cytology, RP, URS biopsies, and contrast-enhanced CT that were incomplete or inconclusive were excluded from the analysis.
When the diagnosis was confirmed by histopathology, a standard radical nephroureterectomy procedure was accomplished through an open approach in the majority of patients with one or two abdominal pararectal incisions, a standard lumbar and lower abdominal incision. Twenty-four cases were performed laparoscopically, and 13 were managed by segmental ureterectomy for solitary functioning renal units.
Tumor characteristics and pathologic evaluation
Tumors were staged according to the 1997 TNM classification. The most conventional 3-tiered World Health Organization grading system was used to determine the pathologic grade by an expert uropathology team. The tumor location was divided into 3 groups: pelvicalyceal, ureteral, and both pelvicalyceal and ureteral. Multifocality was defined as the presence of two tumor foci in noncontiguous locations within the ipsilateral renal unit.
The primary outcome was the overall accuracy of URS biopsy to detect malignancy in patients with ureteral tumors. This was correlated with the reports of contrast-enhanced CT and the final histopathology – the gold standard method of diagnosis. Moreover, the intended outcome was to assess the accuracy with regard to the diagnosis of tumor grade, and how significant tumor grade on URS biopsy was in predicting tumor stage. The secondary outcome was to study the impact of URS on secondary intravesical tumor recurrence and overall survival.
Frequency and percentage were used for nominal and categorical variables. Sensitivity and specificity were calculated by comparing the results of cytology, retrograde, biopsy, and cross-sectional radiology with the final histopathological criteria. When the numbers of false-positive and negative cases were small, the overall accuracy was used more frequently than sensitivity and specificity using standard equations. The Chi-square test was used for nominal variables, and cancer-specific survival (CSS) was evaluated from the date of surgery using the Kaplan–Meier method. The log-rank test was used to study the effect of URS on survival. In all tests, the P value was two sided, and significance was set at P < 0.05. Analysis was performed using commercial computer software SPSS®, version 21 (IBM Corp., Armonk, NY, USA).
| Results|| |
Data of 275 patients were collected. The mean age of the study population was 59 ± 11 years (range, 26–85 years) and 239 (87%) were male. The median follow-up period was 52 months (range, 18–200 months), and the tumor was right sided in 108 cases (44%). The other pathologic tumor characteristics are listed in [Table 1].
|Table 1: Tumor characteristics of 275 patients after surgical management of upper tract urothelial carcinoma|
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Data of RP studies were available for 104 patients, showing filling defects in 96 patients (92%). Data regarding upper tract cytology were available for 119 patients, with 91 reported cases suspicious for transitional cell carcinoma (TCC) and the remaining cases not suspicious, with an overall diagnostic accuracy of 75%.
Complete URS biopsy data were available for 124 patients with a total of 135 biopsies (94 ureteric and 41 pelvicalyceal tumors). To ensure the homogeneity of the cohort and strengthen our results, further analysis was done for 94 ureteric biopsies only. There were no false positives and a total of seven negative results. Only one was a true negative, leaving six false-negative biopsies with an overall diagnostic accuracy of 93%. The false-negative cases had sizable distal ureteric tumors and were operated on based on the imaging diagnosis and significant hydronephrosis.
When matched to the final histopathology, URS the accuracy of biopsies in detecting tumor grade increased as the tumor grade increased [Table 2]. Biopsy diagnosed 10%, 70%, and 92% of GI, II, and GIII, respectively. Upgrading at the final histopathology was a common characteristic of URS biopsy; 70% of the cases were upgraded from GI to GII, 20% from GI to GIII, and 25% from GII to GIII. Biopsy grade was a good predictor for stage; 15/20 (75%) of GI and 43/55 (80%) of GII were noninvasive on final staging, and 9/12 (75%) of GIII were invasive on final staging.
|Table 2: Correlation of ureteroscopy biopsy tumor grading with the final histopathology results, cohort of 94 ureteric biopsies only|
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CT was done in 270 patients, and the overall accuracy was 96% [Table 3]. Seven cases were diagnosed with no UTUC by CT, with six cases proven to be false negative; four ureteral tumors (T1) and one pelvicalyceal tumor (T2) could not be detected by CT, and one renal mass was diagnosed as a renal parenchymal tumor by CT. We then further analyzed the ureteral biopsies cohort, which revealed an overall accuracy of CT of 96%.
|Table 3: Correlation between the computed tomography urography findings and the final histopathological results in 270 patients|
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A total of 126 (46%) patients had bladder recurrence, and the incidence was equal in the patients who did and did not undergo a URS biopsy. In the whole cohort, those with either pelvicalyceal or ureteral tumors developed bladder recurrence. URS did not affect post-UTUC intravesical recurrence (P = 0.9), even after excluding 108 patients who had a history of and/or concomitant bladder tumors (P = 0.7). URS, as a surgical procedure, did not affect CSS in either the short or long term (Breslow = 0.06 and log-rank test = 0.08) [Figure 1].
|Figure 1: Kaplan–Meier curve of cancer-specific survival stratified by ureteroscopy|
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| Discussion|| |
We reported the outcomes of URS as a diagnostic modality for UTUC in a large series including 275 patients at a single tertiary urology institute. Nephroureterectomy and bladder cuff excision are the traditional standard treatments for high-grade/stage disease; however, endoscopic excision and laser ablation of small and uniform tumors, as well as low-grade and low stage disease, have shown satisfactory recurrence-free rates. Our series included a few patients in this category, but more frequently patients with tumors of a larger median size who were not good candidates for endoscopic management. A delay in referring patients to our tertiary institute could be a possible explanation.
Historically, urine cytology is one of the essential diagnostic studies for UTUC. However, recent studies have shown it to be a poor diagnostic tool for UTUC, and the overall accuracy was 75% in the present study. Although RP showed filling defects in 92% of the cases, it lacked specificity.
Confirming low-grade and noninvasive stages of UTUC by histopathology are crucial in decision-making. Hence, clear information about the accuracy of URS in predicting tumor grade/stage is mandatory for practicing urologists. Moreover, URS biopsy is an essential tool during follow-up. The URS biopsy accuracy rate in the present study was higher than that reported by Straub et al. and Guarnizo et al. (74% and 78%, respectively)., Both of their studies had heterogenous patient groups with both renal-pelvic and ureteric tumors, and Guarnizo's series had a small number of patients. Incorporating pelvicalyceal biopsies may lower the accuracy because the tumor may exist in peripheral calyces which are difficult to biopsy. For that reason, we chose to include ureteric tumors only in our study.
Upgrading was high in our series, and similar results have been reported in the literature. Rojas et al. reported 43% of his patients were reclassified from low to high grade at the final pathology. In addition, Wang et al. studied 24 patients with Grade 1 tumors on biopsy and reported that 23 (96%) had their tumor upgraded on the final pathologic examination, with 16/23 (70%) and 7/23 (30%) being upgraded to GII and GIII, respectively. In our cohort, 32/87 cases (36%) were upgraded: from GI to GII in 70%, from GI to GIII in 20%, and from GII to GIII in 25%. Although we used the traditional WHO 1973 grading system, reviews from studies which used the 2004 system have also reported similar upgrading results.
The low accuracy of URS biopsy in predicting tumor stage has been reported in many series in the literature., Yamany et al. reported that URS biopsy missed 25% of the lesions and that 65% of the cases were upstaged. In addition, Guarnizo et al. reported that 45% of their cases were upstaged. The number of reported tumor URS biopsy stage was low in our cohort so that the results are more robust.
Upstaging may also be obvious in the upper tract. The ureter is a narrow tube, and upper urothelial tumors may exist in peripheral calyces, which add to the limitation of ureteroscopic biopsy. In a biopsy, a small amount of tissue is obtained, and the complete tumor in the ureter or the pelvicalyceal system is not excised. Due to these limitations, efforts have been made to try to use URS grade to predict tumor stage., In our series, GI-II and GIII, URS biopsy matched noninvasive and invasive tumors on the final pathology in 77% and 75% of cases, respectively.
URS biopsies may show false-negative results that lower the sensitivity. In general, diagnostic errors of URS biopsy may be beyond the capabilities of URS, especially regarding samples from peripheral calyces or a narrow ureter. In our cohort specifically, patients with false-negative results had sizable distal ureteric tumors, and biopsies were probably taken from tumor necrotic surfaces or the ureteral wall. These cases were operated on based on gross examination and significant hydronephrosis and parenchymal loss. Due to these limitations, a combination of tools can increase the diagnostic accuracy of URS: cross-sectional imaging, cytology, and URS can be used to increase the overall diagnostic accuracy.,
Notably, contrast-enhanced CT was performed in 92% of our patients, and the overall diagnostic accuracy was 96%, even when the analysis included only those in whom URS was performed. Our results are in accordance with many published series., Therefore, we agree with Potretzke et al. who suggested that URS can be omitted as a part of the diagnostic work-up in appropriately selected patients. URS did not alter the surgical plan when the diagnosis was based on cross-sectional studies.
Only six patients had false-negative results by CT in our cohort, of whom four had ureteral tumors. Wang et al. reported that the location of ureteric tumors was an independent factor of tumor undetectability in CT. The ureter is a thin tube with continuous peristalsis, and this may detract from full visualization by contrast media. In addition, the presence of CIS and/or small lesions have been reported to be contributing factors for missed lesions in CT., In our cohort, four false-negative cases in the ureter were staged as T1.
A small filling defect in the renal pelvicalyceal system detected by CT/magnetic resonance imaging with negative urine (washing) cytology is considered to be a challenging case scenario. In such cases, a URS biopsy could be essential before any radical surgery, and the biopsy results could change the treatment plan. Despite the advantages of URS in the diagnosis of UTUC, it is not free of disadvantages. Besides the known complications of URS, such as ureteric injury, perforation, and technical failure, URS also requires hospital admission and carries the risk of anesthetic. Intravesical recurrence postsurgical management of UTUC is common and has been reported in 46% of cases. Many studies have been performed to identify possible risk factors, especially avoidable ones.
URS has been shown to possibly contribute to intravesical recurrence. Liu et al. and Luo et al., concluded that a URS biopsy was an independent risk factor for the development of intravesical recurrence, while Yoo et al. attributed this increased risk to only patients with pelvicalyceal but not ureteric tumors. As suggested, it could increase tumor cell dissemination into the bladder.
In accordance with Sankin et al.'s study, URS in our series did not affect the overall intravesical recurrence rate or CSS. Because of the ongoing debate and in efforts to consolidate our data with regard to the inconsistencies among pervious reports, we excluded 197 patients with a previous history of premanagement and concomitant bladder tumors, confounding factors that could increase the odds of intravesical recurrence. Our results showed that URS was not a statistically significant factor for recurrence (P = 0.7), and it did not affect short- or long-term CSS (Breslow = 0.06 and log-rank test = 0.08).
We could not analyze the biopsy findings for the rest of the patients. Those with tiny growths that were treated by LASER and who had hematuria with large pelvicalyceal tumors that were confirmed by imaging, inaccessible tumors for URS, or tumors that caused gross hydronephrosis with poorly functioning kidneys requiring nephrectomy did not receive a URS biopsy. This study is retrospective, which is similar to most of UTUC series, in view of the rarity of the disease. We did not analyze biopsy size or how size could affect the results; however, it has been reported that biopsy size is not an independent factor and that it does not affect the overall accuracy. In addition, data on URS gross findings were incomplete and so were not included in the study. Despite these limitations, our research can be considered to be the most recent and to provide a comprehensive review with a large number of patients at a tertiary urology institute.
| Conclusion|| |
Our results showed that URS biopsy for ureteral tumors was highly specific with a fair predictive ability for tumor grade, and it could predict tumor stage. URS as a procedure may not increase intravesical recurrence or affect overall survival. On the other hand, URS biopsy may show false-negative results that lower its sensitivity. URS did not alter the surgical plan in this study, especially when radical surgery was chosen based on contrast-enhanced CT.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]