Early-Stage Bladder Cancer Surveillance Does Not Improve Survival If High-Risk Patients Are Permitted to Progress to Muscle Invasion

doi:10.1016/j.urology.2007.02.064

Urology

Volume 69, Issue 6, June 2007, Pages 1068-1072

https://doi.org/10.1016/j.urology.2007.02.064 Get rights and content

Objectives

Surveillance of early-stage bladder cancer (cTis-T1) permits bladder preservation with conservative treatments, using cystectomy to salvage patients with refractory disease. Despite close observation, some tumors progress to muscle invasion during this period. Historically, some believed that cystectomy applied in this setting could provide a better outcome in patients with “early” cT2 disease compared with those with de novo cT2 disease. We compared the pathologic and survival outcomes of patients with high-risk early-stage disease with those of patients with muscle-invasive tumors at presentation.

Methods

A cohort of 422 consecutive patients underwent primary cystectomy for high-risk, progressive, or muscle-invasive bladder cancer. A retrospective review of the demographics, surveillance time, clinical and pathologic parameters, and survival was undertaken. The variables were tested in univariate and multivariate analyses.

Results

Before cystectomy, 182 high-risk patients (44%) had cTis-T1 cancer at diagnosis but did not progress to cT2 disease (group 1); 69 patients (17%) had cTis-T1 that progressed to cT2 during surveillance (group 2); and 167 patients (40%) presented with cT2 tumors (group 3). Groups 2 and 3 had similar patterns of pathologic staging (P = 0.9862), disease-specific survival (P = 0.469), and overall survival (P = 0.643). The rate of understaging was similar in groups 2 and 3 (59% to 60%).

Conclusions

Patients with disease progression to cT2 bladder cancer during surveillance have similar patterns of pathologic staging and survival after cystectomy as those with de novo cT2 disease, likely because of the similar rates of tumor understaging.

Section snippets

Patients

From August 1990 to April 2003, 422 patients underwent primary radical cystectomy as treatment of refractory, recurrent or progressive early-stage (cTis, cTa, or cT1) bladder cancer or frank muscle-invasive (cT2) disease.¹⁶ Patients with Stage cT3 or cT4 disease and those requiring neoadjuvant radiotherapy or systemic chemotherapy were not included. Because of the tumor grade, refractory nature to TURBT and intravesical therapy, and patterns of recurrence and progression, the population was

Patient Categories and Demographics

Table 1 summarizes the analysis of cohort demographics, surveillance, and pathologic parameters. The distributions of surveillance times were positively skewed in groups 1 and 2. The median surveillance time in groups 1 and 2 was 13 and 17 months, and the mean surveillance time was 32 and 48 months, respectively. The median surveillance time in group 3 was 1.8 months. Most patients in groups 1 (64%) and 2 (61%) underwent surveillance for less than 24 months; however, nearly one third of the

Comment

The bladder cancer surveillance schedule outlined by the National Comprehensive Cancer Network guidelines is most effective in detecting the 50% to 70% of recurrent tumors that develop within the first 3 years3, 4 and also at providing predictive information for those with early tumor recurrence.5, 9 This strategy theoretically permits patients to keep a functional bladder and delay cystectomy until progression is evident. The results of the present study suggest that surveillance is unable to

Conclusions

The results of our study have shown that the traditional surveillance paradigm does not offer added survival benefit to patients with high-risk tumors if allowed to progress to muscle-invasive disease, likely relating to the understaging of tumors. New imaging and/or urinary markers are greatly needed to augment and improve traditional surveillance and clinical staging. Surveillance should be used to identify high-risk and early progressive tumors, not to await muscle invasion. Because many

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Cited by (37)

Clinical Trial Protocol for “Replace Cysto”: Replacing Invasive Cystoscopy with Urine Testing for Non–muscle-invasive Bladder Cancer Surveillance—A Multicenter, Randomized, Phase 2 Healthcare Delivery Trial Comparing Quality of Life During Cancer Surveillance with Xpert Bladder Cancer Monitor or Bladder EpiCheck Urine Testing Versus Frequent Cystoscopy
2024, European Urology Open Science
“Replace Cysto” is a multisite randomized phase 2 trial including 240 participants with low-grade intermediate-risk non–muscle-invasive bladder cancer, in which participants will be randomized 1:1:1 to one of two urine marker–based approaches alternating a urine marker test (Xpert Bladder Cancer Monitor or Bladder EpiCheck) with cystoscopy or to frequent scheduled cystoscopy. The primary objective is to determine whether urinary quality of life after surveillance is significantly improved in the urine marker arms. The primary outcome will be the patient-reported urinary quality of life domain score of the validated QLQ-NMIBC24 instrument, measured 1–3 d after surveillance. Exploratory outcomes include discomfort after surveillance, the number of invasive procedures that participants undergo per 1000 person years, complications from these procedures per 1000 person years, nonurinary quality of life, acceptability of surveillance, and bladder cancer recurrence and progression. Comparators include surveillance using (1) the Xpert Bladder Cancer Monitor test, (2) the Bladder EpiCheck urinary marker, or (3) frequent cystoscopy alone. After a negative cystoscopy ≤4 mo following bladder tumor resection, all the participants will undergo surveillance at 6, 12, 18, and 24 mo (with time zero defined as the date of the most recent bladder tumor resection). In the urine marker arms, surveillance at 6 and 18 mo will be performed with the marker. Regardless of the arm, participants will undergo cystoscopy at 12 and 24 mo. End of study for each participant will be their 24-mo cystoscopy. Overall trial duration is estimated at 5 yr from when the study opens to enrollment until completion of data analyses. The trial is registered at clinicaltrials.gov (NCT05796375).
Intravesical Therapy Compared to Radical Cystectomy Among Patients With Non-Muscle Invasive Bladder Cancer Requiring Additional Treatment After Induction BCG
2022, Clinical Genitourinary Cancer
Citation Excerpt :
Alternatively, several salvage therapies have been investigated as a means of bladder preservation. Still, few patients will have durable disease control with currently available salvage intravesical therapy (IVT) agents,10 up to 50% ultimately require a salvage RC,11 and those who progress to muscle-invasive bladder cancer (MIBC) have a lower cure rate after delayed RC.12 Patients with BCG unresponsive bladder cancer face a difficult decision between RC, which is a life-changing, but potentially life-saving, operation, and bladder preservation with IVT.
Many patients with recurrent high-risk non-muscle invasive bladder cancer after intravesical bacillus calmette-guerin (BCG) face a difficult decision between radical cystectomy (RC) or salvage intravesical therapy (IVT). We sought to determine if there is a difference in overall survival RC and IVT after previous treatment with BCG.
We performed a retrospective cohort study of patients with Ta, T1, and Tis bladder cancer treated with induction BCG in the SEER-Medicare dataset from 2000 to 2015. We used a proportional hazards regression model to compare differences in survival between patients having RC and IVT. We adjusted for confounding using a propensity score and stratified our analysis according to timing of treatment and stage at diagnosis.
We identified 3940 patients who received either IVT (79%) or RC (21%) following induction BCG. Among patients treated within 12 months of BCG, there was no significant difference in survival between RC and IVT (HR 0.92, 95% CI 0.81-1.04) and 17% of patients having early IVT ultimately required RC. Among patients treated at least 12 months after BCG, RC was associated with worse survival than IVT (HR 1.19, 95% CI 1.06-1.35) and 10% of patients having late IVT ultimately required RC.
Among patients with bladder cancer who required additional treatments after induction BCG, we did not observe a difference in overall survival between IVT and RC within 12 months of starting BCG. While RC remains the gold-standard for high risk recurrent NMIBC after BCG, bladder preservation with IVT may be appropriate for well-selected patients.
Survival after radical cystectomy: Progressive versus De novo muscle invasive bladder cancer
2020, Cancer Treatment and Research Communications
Despite treatment with radical cystectomy, patients with muscle invasive bladder cancer (MIBC) have a poor survival. It has been reported that survival is worse in NMIBC patients who progressed to MIBC in comparison to patients with de novo MIBC. The objective of this study was to compare survival of progressive versus de novo MIBC. Secondary objective was to explain this difference in survival by clinicopathological factors.
431 patients with MIBC who underwent radical cystectomy between 1998 and 2016 in the Radboudumc, Nijmegen, were retrospectively analyzed. 313 patients were identified with de novo MIBC and 118 with progressive MIBC.
5- and 10-year overall survival (OS) of patients with progressive MIBC was 37% and 20%, respectively. Patients with de novo MIBC had significantly better survival, with a 5- and 10-year OS of 49% and 39%, respectively. Patients with progressive MIBC were more frequently diagnosed with concomitant carcinoma in situ and positive surgical margins in bladder, ureters or urethra. In multivariable analysis that adjusted for these factors, progressive MIBC was associated with a hazard ratio of 1.40 (0.99 – 1.98). Kaplan-Meier survival curves show a detrimental effect of progressive MIBC in patients with pT2 versus pT3–4 tumors and in patients with negative versus positive surgical margins. In multivariable analysis, this effect modification disappeared.
Progressive MIBC is associated with poorer survival than de novo MIBC. Because most patients with progressive MIBC had a history of high risk NMIBC, considering radical cystectomy is most important in the highest risk NMIBC.
It's all about the perspective: Removing bias when co-managing patients with high-grade T1 bladder cancer and localized prostate cancer—A competing risks analysis
2018, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
Other groups have shown that for patients with high-risk NMIBC initially treated with TUR and BCG then salvaged with RC for recurrence or progression, patients who underwent RC within 2 years of the initiation of BCG therapy had improved survival compared to those who underwent RC after 2 years (92% vs. 56%) [14]. Furthermore, patients who progress from NMIBC to MIBC and then undergo cystectomy have consistently worse outcomes than cystectomy patients who present initially with MIBC, stage for stage [15,16]. Clearly, there is variability in the biologic aggressiveness of T1HG tumors [17].
The risk connotation of terminology in influencing decision-making should not be underestimated. For example, “superficial” T1HG bladder cancer has the same poor cancer-specific survival as that conferred by the “highest risk” prostate cancer (Gleason 10, T3b). Co-management of concomitant prostate cancer and non-muscle invasive bladder cancer requires a careful competing risk analysis by both the physician and patient. Herein, we detail how patients and physicians should be careful not to underestimate the risk attributed to “non-muscle invasive” bladder cancer.
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
2016, Urology
Citation Excerpt :
Patients with low-risk, noninvasive bladder cancer have been found to rarely progress to muscle invasion, but those who progress during surveillance have a higher risk of disease-specific mortality.15 Furthermore, patients who progress to muscle-invasive disease during surveillance have similar survival to patients with initial presentation of muscle-invasive bladder cancer.16 The failure of endoscopic surveillance in low-risk bladder cancer to provide a survival benefit suggests that endoscopic surveillance regimens may not be effective at detecting disease progression in a timely manner such that intervention can alter survival outcomes.
To determine survival differences among patients receiving endoscopic vs surgical management for upper tract urothelial carcinoma (UTUC).
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.
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.
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.
EORTC progression score identifies patients at high risk of cancer-specific mortality after radical cystectomy for secondary muscle-invasive bladder cancer
2014, Clinical Genitourinary Cancer
Citation Excerpt :
Although the follow-up of patients with non-MIBC was carried out according to the EAU guidelines in our study with the aim of early detection of muscle invasion,2,17 there was no significant difference in CSS in patients with primary vs. secondary muscle-invasive disease. This has been confirmed in earlier studies.5-10 To our knowledge, currently only 2 studies have been published that could not affirm the same prognosis after RC when comparing patients with primary vs. secondary MIBC.20,21
The aim of this study was to develop a risk stratification of patients with muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC). For this purpose, we compared the cancer-specific mortality (CSM) of patients with primary MIBC and patients with secondary MIBC in different risk groups according to the European Organisation for Research and Treatment of Cancer (EORTC) progression score.
The records of 521 consecutive patients treated with RC for clinical MIBC according to transurethral resection of bladder cancer (TURBT) diagnosis were reviewed. Of the 521 patients, 399 (76.6%) had primary MIBC (study group 1 [SG1]) and 122 (23.4%) had secondary MIBC (study group 2 [SG2]). Patients in SG2 were stratified into risk groups according to the results of the first and last TURBT in non-MIBC using the EORTC progression score.
CSM for patients with primary and secondary MIBC did not differ significantly. Patients in SG2 with the highest risk for tumor stage progression at time of the first and last TURBT in non-MIBC showed a significantly higher CSM after RC compared with patients with low-to-intermediate risk and compared with patients in SG1. In multivariable analyses, stage pT 3/4 (hazard ratio [HR], 2.12; P < .001), lymphovascular invasion (LVI) (HR, 3.47; P < .001), female sex (HR, 1.35; P = .048), and time from diagnosis of MIBC to RC > 90 days (HR, 2.07; P < .001) were significantly associated with higher CSM.
Risk stratification by the EORTC progression score can help to identify those patients with the highest risk of CSM after progression to MIBC and thus enable us to offer these patients a multimodal treatment. Our results need to be verified in large prospective studies.

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: This study was supported by the Robert and Elizabeth Teeter Bladder Cancer Fund.

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Adult urologyEarly-Stage Bladder Cancer Surveillance Does Not Improve Survival If High-Risk Patients Are Permitted to Progress to Muscle Invasion

Objectives

Methods

Results

Conclusions

Section snippets

Patients

Patient Categories and Demographics

Comment

Conclusions

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Early-Stage Bladder Cancer Surveillance Does Not Improve Survival If High-Risk Patients Are Permitted to Progress to Muscle Invasion