The European Association of Urology (EAU) has updated its 2017 guidelines on upper tract urothelial carcinoma (UTUC) based on a review of the latest evidence. Here are some key recommendations from the guidelines, which were published in European Urology by Morgan Rouprêt, MD, of Sorbonne University in Paris, France, and colleagues.

Risk Assessment

Lynch syndrome and exposure to aristolochic acid or smoking all increase the risk for UTUC. The EAU recommends evaluating the patient and family history for Lynch syndrome using Amsterdam criteria. In addition, urologists should ask patients about exposure to smoking and aristolochic acid.

Classification

The guidelines continue to recommend the 2017 tumor node metastasis (TNM) classification.

UTUC Diagnosis

Urologists should perform a urethrocystoscopy to rule out bladder tumor and then perform computed tomography (CT) urography for diagnosis and staging. Selective urinary cytology has high sensitivity for high-grade tumors, including carcinoma in situ. If imaging and cytology are not sufficient for risk stratification of the tumor, diagnostic ureteroscopy and biopsy should be used. Magnetic resonance urography may be used when CT is contraindicated, based on weak evidence.


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UTUC Prognosis

The EAU recommends using preoperative factors to risk-stratify patients and guide therapy decisions. The important prognostic factors include hydronephrosis, tumor multifocality, size, stage, grade, lymph node metastasis, lymphovascular invasion, and variant histology. Older age should not preclude radical nephroureterectomy (RNU).

Kidney-Sparing Management

According to the guideline, patients with low-risk tumors should be offered kidney-sparing therapy. Patients with a solitary kidney or impaired kidney function may also opt for kidney-sparing management rather than RNU when survival is not at stake.

Only weak evidence supports kidney-sparing management of patients with high-risk tumors in the distal ureter.

Management of High-Risk Nonmetastatic UTUC

The EAU recommends RNU with complete removal of the bladder cuff in patients with high-risk disease. Based on weak evidence, an open RNU should be performed for non-organ-confined UTUC to avoid tumor spillage.

If muscle invasion is suspected, urologists should also conduct a template-based lymphadenectomy and offer postoperative systemic platinum-based chemotherapy.

To lower the chance of intravesical recurrence, they should instill a single dose of chemotherapy in the bladder after surgery.

Metastatic UTUC Treatment

According to the guideline, RNU may be offered as a palliative treatment to symptomatic patients with resectable locally advanced tumors.

First-line treatment for cisplatin-eligible patients with metastatic disease includes combination chemotherapy comprising gemcitabine plus cisplatin; methotrexate, vinblastine, adriamycin plus cisplatin (MVAC), preferably with granulocyte colony-stimulating factor (G-CSF); high-dose MVAC with G-CSF; or paclitaxel, cisplatin, and gemcitabine in combination.

Patients unfit for cisplatin should be offered the checkpoint inhibitors pembrolizumab or atezolizumab depending on PD-L1 status. Carboplatin combination chemotherapy should be offered only if PD-L1 is negative.

For second-line treatment, urologists should offer pembrolizumab, atezolizumab, or nivolumab to patients with disease progression during or after platinum-based combination chemotherapy. They should offer vinflunine alone as second-line treatment if immunotherapy or combination chemotherapy is not feasible. Alternatively, they can offer vinflunine as a third or subsequent treatment line.

Treatment Follow-up

Patients who had kidney-sparing treatment rather than RNU require more frequent and rigorous follow-up, according to the authors.

After kidney-sparing management of low-risk tumors, cystoscopy and CT urography should be performed at 3 and 6 months, then annually for 5 years. Ureteroscopy should be performed at 3 months. For patients with high-risk tumors, cystoscopy, urinary cytology, CT urography, and chest CT should be performed at 3 and 6 months, and then yearly. Ureteroscopy and urinary cytology in situ should be performed at 3 and 6 months.

“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,” Dr Rouprêt and colleagues stated.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Rouprêt M, Babjuk M, Burger M, et al. European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol. doi:10.1016/j.eururo.2020.05.042