The European Association of Urology (EAU) has released its annual guideline update on muscle-invasive (MIBC) and metastatic bladder cancer for 2023.
A summary, published in European Urology, reflects evidence from 76 new papers published up to May 2022. It focuses on MIBC surgical treatment, imaging, and histologic subtypes. “It must be emphasised that even though clinical guidelines present the best evidence available, they can never replace clinical expertise when making treatment decisions for individual patients,” J. Alfred Witjes, MD, PhD, of Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, and fellow members of the guideline panel wrote.
Here are some of the notable updates and recommendations on managing MIBC:
The guideline emphasizes the importance of determining if urothelial carcinoma has extended to the urethra because it may affect the choice of urinary diversion.
In radical cystectomy (RC), the specimen should be removed en bloc. For prognosis, the pathologist should describe the location and size of the tumors, surgical margins, ureters, urethra, and prostate.Lymph nodes should be counted and measured. Capsular extension, vascular emboli, and the percentage of lymphovascular invasion should be reported. It’s crucial that pathologists record the percentage of any histologic subtype in the specimen, since bladder cancer variants are associated with worse prognosis and warrant more aggressive management.
To accurately differentiate T1 from T2 disease, clinicians should order magnetic resonance imaging (MRI) of the bladder rather than computed tomography (CT).
Clinicians should use CT or MRI to image the upper urinary tract and lymph nodes and to locate any distant metastasis. CT urography with contrast is best for evaluating the urothelial tract. Whether flurodeoxyglucose positron emission tomography (PET)/CT improves staging of distant metastases is still being studied. PET/MRI might be used in future to detect metastases in patients who cannot receive intravenous iodine contrast.
Clinicians should reserve neoadjuvant chemotherapy (NAC) for cisplatin-eligible patients with T2-T4a cN0 M0. Higher rates of downstaging and pathologic complete response after dose-dense methotrexate, vinblastine, adriamycin, and cisplatin have been reported. Whether NAC improves survival in patients with non-urothelial carcinoma histology needs to be studied further. Neoadjuvant immunotherapy should only be offered within a clinical trial.
In experienced hands, robotic and open radical cystectomy (RC) are comparable and should be performed with lymph node dissection, possibly extended, according to the guideline’s authors. The best surgery outcomes occur at high-volume centers with dedicated teams. Sexual organ-preserving cystectomy (prostate-sparing, prostatic capsule-sparing, seminal vesicle-sparing, or nerve-sparing in men; ovaries, uterus, and vagina in women) results in better functional outcomes in patients with bladder-confined disease. Use shared decision-making to choose a urinary diversion type for an individual patient, considering tumor characteristics, comorbidities, and patient preference.
Frail and comorbid patients warrant evaluation by a multidisciplinary team to identify who would benefit from radical surgery vs bladder-sparing treatment. Cognitive impairment assessments should be part of the work-up.
Trimodal therapy, involving transurethral resection of the bladder tumor (TURBT) and chemoradiation, may yield comparable outcomes to RC in patients with smaller solitary tumors, negative nodes, no extensive or multifocal carcinoma in situ (CIS), no hydronephrosis, and good bladder function.
Adjuvant chemotherapy after surgery improves disease-specific and overall survival in patients with high-risk disease who did not receive neoadjuvant treatment. The US Food and Drug Administration has approved adjuvant nivolumab for patients with high-risk disease. The European Medicines Agency has approved adjuvant nivolumab only for patients with tumor-cell PD-L1 expression of 1% or more. Overall survival data is anticipated.
Based on weak evidence, consider adjuvant radiation therapy in addition to chemotherapy after RC in patients with pT3b-4, positive nodes, or positive margins.
Postoperative histology remains the most important prognostic variable. Using circulating tumor DNA as a prognostic marker remains investigational.
It must be emphasised that even though clinical guidelines present the best evidence available, they can never replace clinical expertise when making treatment decisions for individual patients
For follow-up, clinicians should perform a CT scan every 6 months until year 3, then annually to check for recurrence, including in the upper urinary tract. Individual risk factors may warrant additional imaging. Clinicians also need to monitor for functional complications after urinary diversion, such as incontinence, emptying dysfunction, vitamin B12 deficiency, metabolic acidosis, worsening kidney function, urinary tract infections, stomal stenosis, urolithiasis, and ureteroenteric stricture.
Clinicians need to assess health-related quality of life using validated questionnaires at baseline and after treatment.
Surveillance is required to detect recurrent cancer, which confers poor prognosis. Symptomatic recurrences may be worse than those found during follow-up.
For local recurrence, clinicians should prescribe individualized treatment using radiation therapy, chemotherapy, and surgery, either alone or in combination. They also should treat distant recurrence with chemotherapy. In the case of a single metastasis, they should consider metastasectomy or radiation therapy.
Disclosure: Some guideline authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.