Reliable Predictors of Muscle-Invasive Upper Tract Urothelial Carcinoma before Nephroureterectomy: Why, to Whom, and How Should We Perform Lymph Node Dissection?
Authors: Chavarriaga Julian , Erazo Juan , Mendoza Lupi , Ramirez German , Sejnaui Jorge , Morales Carlos 
Published: June 2021

(1) Introduction and Objective: Upper tract urothelial carcinoma (UTUC) is an uncommon disease, only accounting for 5–10% of all urothelial carcinomas. Current clinical practice guidelines encourage a risk-adapted approach to UTUC management, including lymph node dissection (LND) in patients with muscle-invasive or high-risk tumors. If pathological characteristics could be more accurately predicted from preoperative data, we could optimize perioperative management strategies and outcomes. The aim of this article is to present a detailed revision of preoperative predictors for muscle-invasive UTUC, locally advanced or advanced UTUC, as well as current indications, technique variations, and the reasons as to why LND should be offered to these patients. (2) Methods: We included any kind of studies related to information concerning UTUC, nephroureterectomy, LND, risk factors for recurrence, prediction tools and models for risk stratification. A literature search was conducted following medical subject headings (MeSh), Emtree language, Decs, and text words related. We searched through MEDLINE (OVID), EMBASE (Scopus), LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 2021. Evidence acquisition was presented according to the PRISMA diagram. (3) Results: Preoperative risk factors for either muscle-invasive UTUC (≥pT2), extra urothelial recurrence (EUR), locally advanced disease, or high-risk UTUC can either be derived from ureteroscopic (URS) findings, urine cytology, URS biopsy, or from preoperative radiologic findings. It seems reasonable that LND may provide not only staging and prognostic information but also play a therapeutic role in selected UTUC patients. The patients who benefit the most from LND appear to be those with ≥ pT2 disease, because patients with tumors ≤ pT1 rarely metastasized to LNs. UTUC has characteristic patterns of lymphatic spread that are dependent on tumor laterality and anatomical location. Choosing the right patients for LND, designing and standardizing LND templates based on tumor location and laterality is critical to improve LN yield, survival outcomes, and to avoid under-staging or overtreatment. (4) Conclusions: Patients with muscle-invasive or non-organ-confined UTUC have an extremely high risk for disease recurrence and cancer-specific mortality (CSM). Preoperative factors and prediction models must be included in the UTUC management pathway in our clinical practice to improve the accurate determination of high-risk groups that would benefit from LND. We recommend offering LND to patients with ipsilateral hydronephrosis, cHG, cT1 at URS biopsy and renal sinus fat or periureteric fat invasion. The role of lymphadenectomy in conjunction with radical nephroureterectomy (RNU) is still controversial, given that it may result in overtreatment of patients with pTa-pT1 tumors. However, a clear benefit in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS) has been reported in patients with ≥pT2. We try to avoid LND in patients with cLG, cTa, and no ipsilateral hydronephrosis if the patient is expected to be compliant with the follow up schedule. There is still plenty of work to do in this area, and new molecular and non-invasive tests are necessary to improve risk stratification.