Multidisciplinary Management and Radiotherapy Recommendations for Clinically and Pathologically Node-positive Bladder Cancer

ElsevierVolume 33, Issue 1, January 2023, Pages 35-50Seminars in Radiation OncologyAuthor links open overlay panel

There are limited data regarding the optimal management of patients with pelvic node-positive, but non-metastatic, bladder cancer. Increasing data demonstrate that this is a distinct clinical entity with outcomes bridging between bladder-confined muscle-invasive bladder cancer and metastatic advanced bladder cancer. Guidelines and staging systems have formalized the need to incorporate the unique considerations of management of pelvic node-positive bladder cancer. However, there remains an absence of a definite standard of care. Treatment options include systemic therapy alone, neoadjuvant chemotherapy followed by radical cystectomy, or bladder-preserving trimodality therapy. Furthermore, ongoing studies aim to determine the benefit of incorporating immunotherapy into these treatment paradigms. In this review article, we will discuss the key considerations for management of patients with pelvic node-positive bladder cancer.

Introduction

Cancer patients with regional lymph node metastasis typically have unique outcomes and management paradigms compared to those with localized node-negative disease and those with distant metastasis. Yet, this distinction has not historically been formalized in patients with node-positive bladder cancer.1 In fact, it was not until the eighth edition of AJCC staging in 2017 that patients with pelvic lymph node involvement of bladder cancer were moved from stage IV to stage III, thereby formally acknowledging this as a unique population with distinct outcomes and clinical management considerations.2,3 Despite this formalization, there is a paucity of data to help guide management for this specific cohort. Few trials investigating local therapy with radical cystectomy (RC) or trimodality therapy (TMT) have included clinically node-positive patients, while trials of metastatic bladder cancer frequently do not distinguish outcomes of this cohort. Consequently, there is no consensus standard of care for patients with clinically or pathologically pelvic node-positive bladder cancer. In this review, we present the evidence available to guide management of node-positive bladder cancer and suggest approaches to optimize outcomes in this patient population.

Section snippetsPatterns of Lymphatic Drainage in Bladder Cancer

The regional lymph nodes for bladder cancer include the perivesical, obturator, internal iliac, external iliac, presacral, and common iliac nodal regions.3 The primary lymphatic drainage sites are to the perivesical, obturator, internal iliac, external iliac, and presacral lymph nodal regions, while the secondary drainage site is the common iliac nodal region. Nodes outside of these regions are considered metastatic. The most common regions to be involved based on the pretreatment imaging

Imaging Evaluation for Node-Positive Bladder Cancer

Although imaging is critical for staging, there is a relatively poor correlation between imaging results and occult nodal involvement.29 To this day, computed tomography (CT) is the primary means of determining pelvic nodal involvement. Multiphase contrast-enhanced CT with urinary excretory phase is the gold standard imaging tool for bladder cancer staging.30 This allows for assessing the extent of the primary tumor, any other synchronous primary of the urothelial tract, assessment of lymph

Management Decisions in Node-positive Bladder Cancer

Practice patterns have continued to evolve with widespread variability in the clinical management of clinically or pathologically node-positive bladder cancer. Some multidisciplinary teams favor taking a palliative approach with systemic therapy alone with local therapy reserved for symptom management. Others prefer a curative-intent approach incorporating RC or TMT with or without neoadjuvant chemotherapy (NAC). Below, we discuss the data and rationale supporting the various elements of

Outcomes with Radical Cystectomy and the Role of Peri-operative Chemotherapy

Data describing outcomes with RC in patients with node-positive bladder cancer are from patients who were found to be pathologically node-positive after undergoing RC with pelvic lymph node dissection (PLND) for clinically node-negative disease. Studies of RC alone have suggested relatively poor outcomes. Tarin et al. reported on 591 patients who had RC with PLND with 114 (19%) of patients having pathologically positive nodes. The 5 year recurrence free survival ranged from 35% for pN1 to 25%

Systemic Therapy Alone in Clinically Node-positive Patients

Given that clinically node-positive patients were historically grouped with metastatic patients, it is not surprising that many centers have historically utilized systemic therapy alone. The bulk of prospective data regarding outcomes in patients with clinically node-positive bladder cancer comes from systemic therapy trials of metastatic bladder cancer that included this patient population as a subgroup. However, the specific outcomes of the node-positive patients have not typically been

Conclusion

Node-positive bladder cancer is a relatively rare and distinct clinical entity. Practice patterns are heterogenous with a lacuna in clinical trial data guiding management. Current treatment approaches are based predominately on retrospective data or extrapolation of management from MIBC or metastatic bladder cancer. The three broad underlying approaches are palliative systemic therapy alone, NAC followed by RC, or a TMT bladder preservation approach. Multidisciplinary evaluations and

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