Survival Comparison Between Endoscopic and Surgical Management for Patients With Upper Tract Urothelial Cancer: A Matched Propensity Score Analysis Using Surveillance, Epidemiology and End Results-Medicare Data

doi:10.1016/j.urology.2016.05.033

Urology

Volume 95, September 2016, Pages 115-120

https://doi.org/10.1016/j.urology.2016.05.033 Get rights and content

Objective

To determine survival differences among patients receiving endoscopic vs surgical management for upper tract urothelial carcinoma (UTUC).

Materials and Methods

Using Surveillance, Epidemiology and End Results-Medicare data, patients diagnosed with nonmuscle-invasive, low-grade UTUC as their first cancer diagnosis between 2004 and 2009 were identified. Receipts of endoscopic and surgical interventions were assessed, and patients were separated into surgical or endoscopic management cohorts. Two-to-one propensity score analysis was performed to control for baseline characteristics between groups.

Results

The endoscopic management (n = 151) and matched surgical management (n = 302) groups demonstrated no significant differences in age, gender, race, marital status, Charlson comorbidity index, or year of diagnosis. Endoscopic management was an independent and significant predictor of all-cause and cancer-specific mortality (hazard ratio 1.6 for overall survival [OS], hazard ratio 2.1 for cancer-specific survival [CSS]). Kaplan-Meier estimated survival was significantly lower for endoscopic management, with both OS and CSS curves diverging at approximately 24-36 months. A subset of patients initially receiving endoscopic management went on to receive surgical intervention (80/151 = 53%) at a median of 8.8 months from diagnosis. For these patients, Kaplan–Meier-estimated CSS was not significantly different from those who continued with only endoscopic management, and remained significantly lower than patients who received upfront surgery.

Conclusion

Although initial survival outcomes (first 24 months) are similar for endoscopic and surgical management of nonmuscle-invasive, low-grade UTUC, both CSS and OS are significantly inferior for the endoscopic management group in the longer term. Furthermore, transition from initial endoscopic management to surgical intervention appears to have limited impact on survival.

Section snippets

Identification of Overall Cohort

We assessed SEER-Medicare data for patients diagnosed with nonmuscle-invasive (American Joint Committee on Cancer stage Ta, Tis, T1),¹¹ low-grade UTUC based on diagnosis codes between years 2004 and 2009 with follow-up data available through 2011. We excluded patients with nodal or metastatic disease based on the SEER historical staging system variable. Information on recurrence is not available in the SEER data. Per the SEER grading guidelines,¹² transitional cell carcinoma is classified by a

Results

Table 1 summarizes the baseline clinical information for the patients who received endoscopic management and the matched cohort of patients who received surgical management. As expected, based on the matching algorithm, there were no significant differences in age, gender, race, marital status, Charlson comorbidity index, or year of diagnosis between the 2 groups. In the cohort, 83% of all patients who had definitive surgery had final pathologic stage of T1 or less. Among patients with

Comments

Using propensity score analysis to control for baseline differences, our study aimed to identify survival differences between endoscopic and surgical management for patients diagnosed with nonmuscle-invasive, low-grade UTUC as their first malignancy. We found that patients receiving upfront surgical management had significantly improved OS and CSS, and accordingly endoscopic management was an independent predictor of all-cause and cancer-specific mortality. The significant improvement in OS and

Conclusion

For nonmuscle-invasive, low-grade UTUC, endoscopic management provides similar early (first 24 months) OS and CSS to upfront surgical management. However, after this period of time, survival curves diverge with significantly inferior OS and CSS for patients who received endoscopic management. For patients who eventually underwent surgical intervention after initial endoscopic management, CSS remains significantly inferior to those who received upfront surgical management, and CSS remains

References (28)

J.J. Munoz et al.
Upper tract urothelial neoplasms: incidence and survival during the last 2 decades
J Urol
(2000)
M. Roupret et al.
Comparison of open nephroureterectomy and ureteroscopic and percutaneous management of upper urinary tract transitional cell carcinoma
Urology
(2006)
M.L. Cutress et al.
Endoscopic versus laparoscopic management of noninvasive upper tract urothelial carcinoma: 20-year single center experience
J Urol
(2013)
M. Roupret et al.
European guidelines on upper tract urothelial carcinomas: 2013 update
Eur Urol
(2013)
A.J. Gadzinski et al.
Long-term outcomes of nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma
J Urol
(2010)
A.K. Smith et al.
Inadequacy of biopsy for diagnosis of upper tract urothelial carcinoma: implications for conservative management
Urology
(2011)
M. Charlson et al.
Validation of a combined comorbidity index
J Clin Epidemiol
(1994)
K.D. Linton et al.
Disease specific mortality in patients with low risk bladder cancer and the impact of cystoscopic surveillance
J Urol
(2013)
C.T. Lee et al.
Early-stage bladder cancer surveillance does not improve survival if high-risk patients are permitted to progress to muscle invasion
Urology
(2007)
A.Z. Weizer et al.
Progression of disease despite good endoscopic local control of upper tract urothelial carcinoma
Urology
(2007)

G.A. Brown et al.

Ability of clinical grade to predict final pathologic stage in upper urinary tract transitional cell carcinoma: implications for therapy

Urology

(2007)

F.X. Keeley et al.

Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma

J Urol

(1997)

E. Guarnizo et al.

Ureteroscopic biopsy of upper tract urothelial carcinoma: improved diagnostic accuracy and histopathological considerations using a multi-biopsy approach

J Urol

(2000)

J.C. Brien et al.

Preoperative hydronephrosis, ureteroscopic biopsy grade and urinary cytology can improve prediction of advanced upper tract urothelial carcinoma

J Urol

(2010)

Cited by (23)

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update
2023, European Urology
The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC.
To provide an overview of the EAU guidelines on UTUC as an aid to clinicians.
The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recurrence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts.
Even though data are accruing, for many areas there is still insufficient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatin-ineligible patients. Patients with PD-1/PD-L1–positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab).
These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours.
Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist.
Oncologic and Safety Outcomes for Endoscopic Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An Updated Systematic Review and Meta-analysis
2023, European Urology Focus
Citation Excerpt :
Detailed search terms, the inclusion and exclusion criteria, and the statistical analyses are described in full in the Supplementary material. Overall, 13 studies [7–19] were included in the review, of which five were eligible for meta-analysis. The study characteristics are shown in Table 1.
We systematically reviewed the literature and summarized oncologic and safety outcomes for endoscopic management (EM) compared to radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). Studies comparing oncologic and/or safety results for EM versus RNU in patients with UTUC were included in our review. Overall, 13 studies met the criteria, and five studies were included in a meta-analysis using adjusted hazard ratios (HRs) for overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). EM was associated similar OS (HR 1.27, 95% confidence interval [CI] 0.75–2.16), CSS (HR 1.37, 95% CI 0.99–1.91), and BRFS (HR 0.98, 95% CI 0.61–1.55) to RNU, while 28–85% of patients treated with EM experienced upper tract recurrence across the studies. EM required more interventions with a higher cumulative risk of complications and lower likelihood of renal preservation. In summary, EM for low-grade UTUC had comparable survival outcomes to RNU at the cost of higher local recurrence rates resulting in a need for long-term rigorous surveillance and repeated interventions.
For selected cases of cancer in the upper urinary tract, surgical treatment via a telescope inserted through the urethra or the skin (endoscope) results in cancer control outcomes that are comparable to those after removal of the kidney and ureter. However, because of its higher rate of local recurrence, this approach requires repeated endoscopic treatment sessions. Patients should be well informed about these issues to help in shared decision-making.
Endoscopic Management of Low-Grade Upper Tract Urothelial Carcinoma: Characterizing the Long-term Burden of Care in Comparison to Radical Nephroureterectomy
2022, Urology
To compare procedure burden, oncologic, surgical and renal-function outcomes between patients with low-grade upper urothelial cancer (UTUC) who were referred for either radical management (RM) or kidney-sparing endoscopic management (EM).
We retrospectively reviewed data of all patients treated for UTUC at our tertiary medical center between 2000 and 2018 and selected patients diagnosed with unilateral low-grade UTUC.
Twenty-four patients were treated with EM and 37 with RM. Surgical and oncologic risk factors were similar between the arms except for tumor size. Mean follow-up was 4.9 ± 3.4 years. The 5-year overall-survival rate was 85% with EM and 84% with RM (P = .707). Metastasis-free and cancer-specific survival were also similar (P = .994, P = .960). End-of-follow-up average glomerular filtration rates were 58.7 ± 21.5 and 49.2 ± 22.1 mL/min/1.73 m², respectively (P = .12). Ninety-two percent of patients managed endoscopically had local recurrences, with an average of 3.2 recurrences per patient. Four (17%) patients underwent salvage radical nephroureterectomy. Procedure burden was higher with EM, having 6.5 ± 4.4 operations and 344 ± 272 minutes under anesthesia compared with 1.9 ± 0.4 operations (P <.0001) and 213 ± 84 minutes under anesthesia (P = .031) with RM. Cost-of-care analysis revealed higher costs for EM in both private and publicly funded medical insurance plans.
Patients undergoing endoscopic management had an 83% chance of preserving their kidney and an 81% chance of 5-year metastasis-free survival at a cost of 6.5 ± 4.4 operations during a mean follow-up of 4.9 ± 3.4 years. Our findings support EM for low-grade UTUC as a valid option from oncological aspects but highlight the associated costs.
Upper urothelial tract high-grade carcinoma: comparison of urine cytology and DNA methylation analysis in urinary samples
2021, Human Pathology
Citation Excerpt :
Low-risk cancers can be effectively treated with kidney sparing endoscopic approaches, but they could need stringent surveillance as second look or frequent ureter-renoscopy [7]. Nevertheless, a risk of disease progression remains with endoscopic management due to the suboptimal performance of imaging and biopsy for risk stratification and tumor biology [8]. For all these reasons, true grade identification and risk classification are the key points in therapeutic planning.
Numerous studies showed that bladder urothelial carcinoma and upper urothelial tract carcinoma (UTUC) display clinical and genomic similarities. In order to analyze that the same panel of biomarkers used in the diagnosis of bladder urothelial carcinoma could be suitable for early detection of UTUC, we performed a retrospective study in which we analyzed Bladder EpiCheck scores in the urinary samples obtained by selective ureteral catheterization in a high-grade UTUC cohort, correlating the results with urinary cytology and diagnostic urethral biopsies. The present study represents a retrospective analysis of 82 patients with clinically localized high-grade UTUC (60 renal pelvis UTUC, 22 ureter UTUC) who had undergone a radical nephroureterectomy (RNU) at our Urology department from June 2018 to November 2020. Before any surgical procedure, one sample of urine, obtained by selective ureteral catheterization, was collected for each patient for cytological examination, and the remaining material was stored for the Bladder EpiCheck test. Our results showed that the sensitivity of the methylation test for high-grade UTUC was about 97.4%, significantly higher than the sensitivity of urinary cytology either considering the HGUC cytological diagnosis or including in the positive cases the SHGUC cytological diagnosis (97.4% versus 59% or 70.5%). The methylation analysis of urinary samples may represent a valid tool in the diagnostic process of patients with suspected UTUC. In cases with a difficult clinical decision after upper urinary tract biopsy and cytology, the methylation test could assist in the clinical management of UTUC patients.
European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update
2021, European Urology
Citation Excerpt :
The patient should be informed of the need and be willing to comply with an early second-look URS [136] and stringent surveillance; complete tumour resection or destruction is necessary [136]. Nevertheless, a risk of disease progression remains with endoscopic management due to the suboptimal performance of imaging and biopsy for risk stratification and tumour biology [137]. Percutaneous management can be considered for low-risk UTUC in the renal pelvis [134,138] (LE: 3).
The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice.
To provide an overview of the EAU guidelines on UTUC as an aid to clinicians.
The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract carcinoma, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, adjuvant treatment, instillation, recurrence, risk factors, and survival. References were weighted by a panel of experts.
Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification as well as for radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumour and two functional kidneys. After radical nephroureterectomy, cisplatin-based chemotherapy is indicated in locally advanced UTUC.
These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours.
Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.
Modern Kidney-Sparing Management of Upper Tract Urothelial Carcinoma
2023, Cancers

View all citing articles on Scopus

: Financial Disclosure: The authors declare that they have no relevant financial interests.

: Funding Support: This study was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences of the National Institutes of Health. Grant Number R24 HS19455 through the Agency for Healthcare Research and Quality. Barnes-Jewish Hospital Foundation/ICTS Clinical and Translational Science Research award (UL1 RR024992); Washington University KL2 Career Development Awards Program (KL2 TR000450); and the National Institute of Diabetes and Digestive and Kidney Diseases Clinical Investigator Award (1K08DK097302-01A1).

View full text

OncologySurvival Comparison Between Endoscopic and Surgical Management for Patients With Upper Tract Urothelial Cancer: A Matched Propensity Score Analysis Using Surveillance, Epidemiology and End Results-Medicare Data

Objective

Materials and Methods

Results

Conclusion

Section snippets

Identification of Overall Cohort

Results

Comments

Conclusion

J Urol

Urology

J Urol

Eur Urol

J Urol

Urology

J Clin Epidemiol

J Urol

Urology

Urology

Urology

J Urol

J Urol

J Urol

Oncology
Survival Comparison Between Endoscopic and Surgical Management for Patients With Upper Tract Urothelial Cancer: A Matched Propensity Score Analysis Using Surveillance, Epidemiology and End Results-Medicare Data