Endoscopic management of upper tract urothelial carcinoma: Improved prediction of invasive cancer using a ureteroscopic scoring model
Introduction
Although it is a rare genitourinary malignancy, accounting for only 5–10% of urothelial tumors, the incidence of upper tract urothelial carcinoma (UTUC) in the United States has slowly increased over the past 30 years [1], [2]. The current gold standard treatment of UTUC is radical nephroureterectomy (RNU) with bladder cuff excision [3]. Conservative management treatments can be considered in elective cases (normal contralateral kidney), as well as imperative cases of low-risk UTUC (e.g., renal insufficiency, bilateral disease, or solitary functional kidney) [3]. Studies show that these approaches can achieve acceptable oncologic outcomes along with preservation of renal function [4], [5], [6], [7], [8].
The substantial negative impact of chronic kidney disease on cardiovascular events and overall mortality has led to the use of nephron-sparing surgeries for the treatment of small renal cell carcinoma [9], [10], and partial nephrectomy has become a preferred option when technically feasible [11]. By extrapolation of the results in patients with renal cell carcinoma, conservative nephron-sparing management could be further indicated for many UTUC patients [12].
Although there is a growing interest in the conservative management of UTUC, it remains essential to select the appropriate patients for these approaches. However, the clinical staging of UTUC might not be as precise as the staging of renal cell carcinoma and despite advancements in imaging, the accurate T-staging of UTUC remains challenging. Recent recommendations suggest the following selection criteria for the conservative management of UTUC: low grade, unifocal tumor <1 cm, no evidence of infiltrative lesion on imaging, and no hydronephrosis [3], [13], [14], [15]. Ureteroscopic biopsies are necessary for accurate staging in order to determine if conservative management is appropriate. The presence of a high-grade tumor, as determined by biopsy, has been considered an important predictor of UTUC. However, there is a lack of evidence for the role of tumor depth in predicting UTUC, which is likely due to the difficulty in obtaining representative lamina muscularis tissue [16]. We assumed that invasive UTUC should be excluded from conservative management. The current study aimed to investigate the clinical and ureteroscopic factors associated with UTUC, and to establish a model for the improved prediction of invasive UTUC using a newly proposed ureteroscopic scoring system.
Section snippets
Materials and methods
This study was performed with the approval of the Internal Review Board of Samsung Medical Center, Sungkyunkwan University School of Medicine (IRB No. 2015-06-202). Patient records/information was anonymized and de-identified prior to analysis.
Results
Median age at RNU was 66 (57–74) years, and 78.5% of the patients were male. A history of prior or concurrent bladder tumors was present in 26.2% of patients. Tumors were distributed in the renal pelvis (40.7%), ureter (51.2%), and both (8.1%). Hydronephrosis and local invasion were found on imaging in 58.7% and 31.4% of patients, respectively. Overall, 57% of patients had positive urine cytology. A high-grade tumor, CIS, or stromal invasion was found in 32.6%, 10.5%, and 48.8%, respectively,
Discussion
The present study demonstrates that the tumor depth (stromal invasion) as determined by ureteroscopic examination is a more important factor in predicting invasive UTUC than the presence of a high-grade tumor. Interestingly, high-grade tumor presence remained statistically insignificant on multivariate analysis. This may be due to an interaction with tumor depth suggesting that, if the stromal invasion is excluded, high-grade tumor presence could be a significant predictor along with the other
Conflict of interest
None.
Acknowledgements
Statistical analyses were performed by aid of Sin-Ho Jung, Ph.D., and Sun-Kyu Choi, M.S., Biostatistics and Clinical Epidemiology Center, Samsung Medical Center.
References (32)
- et al.
European guidelines on upper tract urothelial carcinomas: 2013 update
Eur. Urol.
(2013) - et al.
Radical nephroureterectomy versus endoscopic procedures for the treatment of localised upper tract urothelial carcinoma: a meta-analysis and a systematic review of current evidence from comparative studies
Eur. J. Surg. Oncol.
(2014) - et al.
Long-term outcomes of nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma
J. Urol.
(2010) - et al.
Conservative management of upper tract urothelial carcinoma in France: a 2004-2011 national practice report
Eur. Urol.
(2013) - et al.
Nephron-sparing techniques independently decrease the risk of cardiovascular events relative to radical nephrectomy in patients with a T1a-T1b renal mass and normal preoperative renal function
Eur. Urol.
(2015) - et al.
EAU guidelines on renal cell carcinoma: 2014 update
Eur. Urol.
(2015) - et al.
Preoperative hydronephrosis, ureteroscopic biopsy grade and urinary cytology can improve prediction of advanced upper tract urothelial carcinoma
J. Urol.
(2010) - et al.
A new proposal to risk stratify urothelial carcinomas of the upper urinary tract (UTUCs) in a predefinitive treatment setting: low-risk versus high-risk UTUCs
Eur. Urol.
(2014) - et al.
EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013
Eur. Urol.
(2013) - et al.
A review of current guidelines and best practice recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group
J. Urol.
(2011)
Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma
J. Urol.
Ability of clinical grade to predict final pathologic stage in upper urinary tract transitional cell carcinoma: implications for therapy
Urology
Ureterorenoscopic biopsy and urinary cytology according to the 2004 WHO classification underestimate tumor grading in upper urinary tract urothelial carcinoma
Urol. Oncol.
Preoperative hydronephrosis grade independently predicts worse pathological outcomes in patients undergoing nephroureterectomy for upper tract urothelial carcinoma
J. Urol.
The effect of tumor location on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center
Eur. Urol.
The protective role of renal parenchyma as a barrier to local tumor spread of upper tract transitional cell carcinoma and its impact on patient survival
J. Urol.
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Novel Classification for Upper Tract Urothelial Carcinoma to Better Risk-stratify Patients Eligible for Kidney-sparing Strategies: An International Collaborative Study
2022, European Urology FocusCitation Excerpt :Chen et al reported that tumors without multifocality (hazard ratio 1.639; p = 0.028) were a predictive factor for muscle-invasive UTUC, which was not found in our cohort. However, several studies have reported that tumor multifocality is not predictive of muscle-invasive disease [11,13–16]. Tumor size was not an independent predictive factor for muscle invasion at RNU in our multivariate analysis.
Phase II multi-center trial of optical coherence tomography as an adjunct to white light cystoscopy for intravesical real time imaging and staging of bladder cancer
2021, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :In UTUC, risk stratification is a critical determinant of neoadjuvant chemotherapy, regional lymph node dissection during nephroureterectomy, and nephron-sparing surgery [19,20]. However, the clinical staging of UTUC is limited by the poor accuracy of ureteroscopy and inconclusive histopathology although various attempts have been made [21,22]. The use of OCT together with ureteroscopy for detecting UTUC was previously evaluated.
Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe
2020, UrologyCitation Excerpt :Normal mucosa was not stained by ICG-Var3 pHLIP, nor were nonmalignant lesions such as ureteritis cystica. Cross-sectional imaging and traditional white-light endoscopic visual have historically demonstrated poor performance for the diagnosis and staging of UTUC.22-24 Recognizing the need for better and more accurate diagnostic methods, new technologies have been proposed.
Cryobiopsy in the Upper Urinary Tract: Preclinical Evaluation of a Novel Device
2019, UrologyCitation Excerpt :Obtaining representative tissue samples from the UUT by URS biopsy represents a major challenge. Biopsy samples are often insufficient in size and tissue quality, precluding valid pathologic evaluation and limiting diagnostic accuracy with regard to stage and grade.1,4-6,8,17-19 In a series of patients who underwent RNU, pathologic upstaging occurred in up to 45% of tumors preoperatively classified as stage pTa.20
Multi-institutional Evaluation of Upper Urinary Tract Biopsy Using Backloaded Cup Biopsy Forceps, a Nitinol Basket, and Standard Cup Biopsy Forceps
2018, UrologyCitation Excerpt :Given our findings, optimal urothelial biopsy is likely achieved on a case-by-case basis, noting the location, morphology, and size of the biopsy to be obtained. Jeon et al30 found that invasion of the lamina propria was present in 84% of patients with >pT2 stage UTUC, albeit with the standard cup forceps obtaining lamina propria in half of its specimens, which is similar to our findings (Table 1). Thus, the presence of lamina propria cannot be understated and reinforces routine ureteroscopic evaluation for UTUC and may improve the selection of patients for neoadjuvant chemotherapy if pursuing NU.