The role of surgery in metastatic bladder cancer (BCa) is unclear.
Objective
In this collaborative review article, we reviewed the contemporary literature on the surgical management of metastatic BCa and factors associated with outcomes to support the development of clinical guidelines as well as informed clinical decision-making.
Evidence acquisition
A systematic search of English language literature using PubMed-Medline and Scopus from 1999 to 2016 was performed.
Evidence synthesis
The beneficial role of consolidation surgery in metastatic BCa is still unproven. In patients with clinically evident lymph node metastasis, data suggest a survival advantage for patients undergoing postchemotherapy radical cystectomy with lymphadenectomy, especially in those with measurable response to chemotherapy (CHT). Intraoperatively identified enlarged pelvic lymph nodes should be removed. Anecdotal reports of resection of pulmonary metastasis as part of multimodal approach suggest possible improved survival in well-selected patients. Cytoreductive radical cystectomy as local treatment has also been explored in patients with metastatic disease, although its benefits remain to be assessed.
Conclusions
Consolidative extirpative surgery may be considered in patients with clinically evident pelvic or retroperitoneal lymph nodal metastases but only if they have had a response to CHT. Surgery for limited pulmonary metastases may also be considered in very selected cases. Best candidates are those with resectable disease who demonstrate measurable response to CHT with good performance status. In the absence of data from prospective randomized studies, each patient should be evaluated on an individual basis and decisions made together with the patient and multidisciplinary teams.
Patient summary
Surgical resection of metastases is technically feasible and can be safely performed. It may help improve cancer control and eventually survival in very selected patients with limited metastatic burden. In a patient who is motivated to receive chemotherapy and to undergo extirpative surgical intervention, surgery should be discussed with the patient among other consolidation therapies in the setting of multidisciplinary teams.
Introduction
In Western countries, muscle-invasive disease accounts for about one-fourth of newly diagnosed urothelial bladder cancer (BCa) cases and approximately 10–30% of nonmuscle invasive BCa that have progressed. Nearly half of patients with muscle-invasive BCa will relapse despite intensive therapies, eventually succumbing to their disease [1], [2], [3], [4]. Approximately, three-fourths of these patients relapse with distant failure, with the remaining one-fourth experiencing local recurrence [4], [5]. In addition, somewhere between 5% and 15% of patients present with unresectable or metastatic disease at time of diagnosis [6]. When possible, for all patients with primary or secondary metastatic cancer, systemic platinum-based combination chemotherapy (CHT) is the standard treatment [2] resulting in initial response rates of 40–70%, but long-term survival of less than 15% within 5 yr [7], [8]. In addition to the unfavorable response to systemic CHT, nearly half of patients are already unfit for this regimen due to renal and other comorbid conditions.
Surgical extirpation of the primary or metastases is part of a multimodal approach in various malignancies yielding potentially better survival and/or quality of life. This concept is increasingly being considered in urology from accepted entities such as testis and kidney cancers to more recently, prostate cancer [5], [9]. Nevertheless, the role of surgery in metastatic urothelial carcinoma (UC) is not yet established with most of the experience being accrued from retrospective uncontrolled studies [2]. No pertinent prospective randomized trials have been published on this topic. Therefore, there is a need to better delineate the evidence-based potential oncological benefit of surgical extirpation of the primary in metastatic setting and of metastasectomy.
To address this need, we performed a systematic review of the role of surgery in patients with clinically node-positive BCa, distant metastasectomy, as well as cytoreductive radical cystectomy (RC).
Section snippets
Evidence acquisition
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocols [10]. A systematic literature search of the PubMed-Medline and Scopus databases was performed on November 2016, including literature from 1999 through 2016. We included English language articles only. The search strategy included broad terms in isolation or in combination: “metastatic bladder cancer,” “metastatic urothelial carcinoma,” “locally advanced
Evidence synthesis
A total of 1430 unique articles were identified, of which 28 were selected and critically analyzed for evidence synthesis based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocols (Fig. 1) [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38].
Conclusions
Metastatic BCa is still a lethal disease with little improvement in outcomes since the introduction of cisplatin-based combination CHT. Cumulative but still limited evidence suggests a role for surgery and/or other consolidation therapies in managing a subgroup of patients with metastatic BCa as an integral part of sequenced multidisciplinary approach. Results are consistently pointing toward improved survival in patients with low volume disease after measurable response to CHT in the lung,
2024, Urologic Oncology: Seminars and Original Investigations
Recent studies have highlighted the overall survival (OS) benefit of cytoreductive radical cystectomy (CRC) in metastatic bladder cancer (mBCa). Cytoreductive surgery has been established in other urologic cancers. However, the efficacy of CRC and optimal criteria for patient selection in mBCa is unclear. This study investigated the oncologic efficacy of CRC, particularly emphasizing the location and number of metastasis sites as a predictor of survival and treatment response.
A retrospective analysis of cT2-4N0-3M1 mBCa patients treated with multiagent chemotherapy between 2004 and 2019 was conducted using the National Cancer Database. Patients were classified by additional treatment with CRC or conservative local treatment (CLT), consisting of transurethral resection of bladder tumor, radiation, or no local treatment and propensity score (PS) matched. Kaplan-Meier analysis and multivariate Cox Proportional Hazards model assessed the effect of CRC or CLT on OS within the matched cohort and in four subgroups (1) patients with only distant lymph node (LN) metastasis vs. any organ metastasis, (2) patients with single metastasis vs. multiple metastases. Sensitivity analysis estimated the influence of unmeasured confounders on CRC OS benefit.
Propensity matching yielded 247 and 251 patients treated with CRC and CLT, respectively. Median OS in patients who received CRC was greater than that of patients treated with CLT (20.4 months vs. 12.0 months, P < 0.001). CRC was associated with reduced mortality risk in patients with only distant LN metastases (HR = 0.545, P = 0.039), any organ metastasis (HR = 0.421, P < 0.001), and single visceral metastasis (HR = 0.483, P = 0.002). However, CRC did not significantly improve OS in patients with multiple metastases (HR = 0.501, P = 0.064).
These findings demonstrate an OS benefit of CRC with multiagent chemotherapy and pinpoint multiple visceral metastases as a potential contraindication for CRC. Although limited by the influence of unmeasured confounders, these findings may inform future prospective investigations into CRC.
Unlike other cancers, the concept of oligometastatic disease (OMD) in bladder cancer (BC) has not been systematically investigated. There is therefore a need to develop universally accepted definitions and guidelines for the management of oligometastatic BC (OMBC).
To conduct a systematic review to assist a European consensus group in producing a definition of OMBC and to provide recommendations on staging and local therapies.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Abstracts for articles focused on BC that addressed the issue of OMBC and provided a definition of oligometastatic status were selected. We collected data on the number of metastases, the number of metastases per organ, the number of organs involved, and metastatic sites that were excluded.
Sixteen eligible articles were retrieved (9 retrospective series involving 330 patients, 4 reviews, 1 consensus statement, 1 guideline paper, and 1 ongoing prospective phase 2 trial). A maximum of three to five metastatic lesions were compatible with the definition of OMBC. The number of organs involved and lesion size were not universally included in the OMBC definitions. OMD categories studied included synchronous OMBC, oligorecurrence, and oligoprogression. 18F-Fluorodeoxyglucose positron emission tomography combined with computed tomography was used in addition to conventional imaging for OMD detection. Surgery and radiotherapy were both used. Systemic chemotherapy was also used in all studies.
There is little information on OMBC in the literature. Our systematic review revealed that only three to five metastatic sites amenable to surgery or radiotherapy that respond to systemic therapy is the setting most frequently chosen for a combination of systemic treatment and metastases-directed therapy. This setting could represent a basis for future prospective studies on OMBC.
Oligometastatic bladder cancer is a disease state in which favorable outcomes can be expected after a treatment combination of systemic therapy, plus surgery and/or radiotherapy for sites of bladder cancer metastasis. Our systematic review showed a lack of meaningful evidence to define this disease state. There is an urgent need to develop organized research in this field.
2022, Urologic Oncology: Seminars and Original Investigations
Surgical resection of oligometastatic disease has been shown to be associated with an improved survival in other malignancies, though its role is not established in metastatic urothelial carcinoma (mUC). We sought to examine utilization trends of metastasectomy in mUC and associated outcomes using the NCDB database.
We queried the NCDB from 2004 to 2016 for patients with metastatic urothelial carcinoma who had undergone metastasectomy. The annual utilization trend of metastasectomy was evaluated by linear regression. We compared overall survival (OS) between propensity score matched patients who had undergone metastasectomy and those who had not using two-sided log-rank and Cox regression models. We also performed sensitivity analyses on subcohorts of mUC.
The utilization rate of metastasectomy in mUC was 7% and did not change significantly over time. Patients who received metastasectomy on average were younger, had >cT3 disease, had radical surgery to the primary tumor, and received systemic therapy. After propensity score matching, metastasectomy was not associated with an OS benefit for mUC patients (HR, 0.94; 95% CI, 0.83 to 1.07; P=0.38). Stratified subgroup analysis based on systemic therapy, radical surgery to primary tumor, clinical N stage, and primary location of disease did not show an OS benefit of metastasectomy.
Metastasectomy is uncommonly used, though utilization has persisted over more than a decade. Despite selection biases and residual confounding favoring patients undergoing metastasectomy, we found similar OS among these individuals and those who did not undergo metastasectomy.
