Reply to Jue et al. Overcoming Understaging and Undergrading in Upper Tract Urothelial Carcinoma. Comment on “Ghoreifi et al. Modern Kidney-Sparing Management of Upper Tract Urothelial Carcinoma. Cancers 2023, 15, 4495”
Alireza Ghoreifi, Reza Sari Motlagh, Gerhard Fuchs

Abstract
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsBladder and Urothelial Cancer Treatments · Renal cell carcinoma treatment · Urinary and Genital Oncology Studies
We appreciate the comments made by Jue et al. on our manuscript ‘Modern kidney-sparing management of upper tract urothelial carcinoma (UTUC)’ [1]. The authors judiciously highlighted the limitations of ureteroscopic biopsy in patients with UTUC. Despite certain risks like undergrading and understaging, a substantial correlation between tumor grade upon ureteroscopic biopsy and the final pathology exists, especially for high-grade tumors. In addition, the detection of clinical high-grade tumors and subepithelial connective tissue invasion in ureteroscopic biopsy has demonstrated a moderate and strong correlation with invasive UTUC, respectively [2]. Hence, the recent American Urological Association (AUA) guidelines strongly recommend the diagnostic ureteroscopy and biopsy of any identified lesion in patients with suspected UTUC [3]. It is worth noting that preoperative clinical staging remains challenging to assess given the limitations of ureteroscopy and other currently available diagnostic modalities, including cross-sectional imaging and urine cytology. Therefore, both AUA and European Association of Urology (EAU) guidelines recommend a risk stratification model to classify patients as being at low- or high-risk of invasive disease (pT2 or greater) [3,4]. This model will be further used for decision making in systemic and surgical treatments, favoring nephron-sparing therapies in patients with low-risk disease.
To address the limitations of ureteroscopic biopsy for proper tissue sampling, Jue et al. proposed en-block enucleation as a potential solution. While the feasibility of this approach has been demonstrated in a few case reports [5,6], offering the advantage of enhanced histopathological information, its indications and oncological safety remain to be determined. Technical considerations to avoid perforation and identifying the appropriate margin of resection are major challenges of this procedure, especially in ureteral tumors. Furthermore, the feasibility and efficacy of this approach in multifocal and flat lesions is not clear.
Despite the crucial role of ureteroscopic biopsy in the diagnosis and risk stratification of patients with UTUC, it significantly increases the risk of intravesical recurrence following radical nephroureterectomy [7]. Using a ureteral access sheath has the potential to mitigate this risk by reducing pelvicalyceal hydrostatic pressure; however, the advantages of this approach require further validation [8]. Considering these caveats, efforts have been made in recent years to explore novel diagnostic and prognostic modalities. Recent studies have shown promising results in this context, particularly with the use of non-invasive modalities such as blood- and urine-based genomic and epigenetic biomarkers [9,10]. Future investigations are warranted to determine the optimal approach for the diagnosis of patients with UTUC.
The reference list from the paper itself. Each links out to its DOI / PubMed record.
- 1Jue J.S. Alameddine M. Armenakas N.A. Overcoming Understaging and Undergrading in Upper Tract Urothelial Carcinoma. Comment on Ghoreifi et al. Modern Kidney-Sparing Management of Upper Tract Urothelial Carcinoma. Cancers 2023, 15, 4495 Cancers 202416100210.3390/cancers 16051002 PMC 1093149138473362 · doi ↗ · pubmed ↗
- 2Subiela J.D. Territo A. MercadéA. Balana J. Aumatell J. Calderon J. Gallioli A. González-Padilla D.A. Gaya J.M. Palou J. Diagnostic accuracy of ureteroscopic biopsy in predicting stage and grade at final pathology in upper tract urothelial carcinoma: Systematic review and meta-analysis Eur. J. Surg. Oncol.2020461989199710.1016/j.ejso.2020.06.02432674841 · doi ↗ · pubmed ↗
- 3Coleman J.A. Clark P.E. Bixler B.R. Buckley D.I. Chang S.S. Chou R. Hoffman-Censits J. Kulkarni G.S. Matin S.F. Pierorazio P.M. Diagnosis and Management of Non-Metastatic Upper Tract Urothelial Carcinoma: AUA/SUO Guideline J. Urol.20232091071108110.1097/JU.000000000000348037096584 · doi ↗ · pubmed ↗
- 4Rouprêt M. Seisen T. Birtle A.J. Capoun O. Compérat E.M. Dominguez-Escrig J.L. Andersson I.G. Liedberg F. Mariappan P. Mostafid A.H. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update Eur. Urol.202384496410.1016/j.eururo.2023.03.01336967359 · doi ↗ · pubmed ↗
- 5Jue J.S. Armenakas N.A. Upper Tract Tumor En Bloc Enucleation: A Novel Approach to the Diagnosis and Management of Upper Tract Urothelial Carcinoma Urology 202317419620010.1016/j.urology.2023.01.00636681329 · doi ↗ · pubmed ↗
- 6Shoen E. Zollinger B. Gresham T. Rezaei K.M. Whalen M. Use of the T-1470 Lite Touch TM Laser in the En Bloc Resection of an Upper Tract Urothelial Cancer Case Rep. Urol.2021202166233263357505610.1155/2021/6623326 PMC 7857907 · doi ↗ · pubmed ↗
- 7Katims A.B. Say R. Derweesh I. Uzzo R. Minervini A. Wu Z. Abdollah F. Sundaram C. Ferro M. Rha K. Risk Factors for Intravesical Recurrence after Minimally Invasive Nephroureterectomy for Upper Tract Urothelial Cancer (ROBUUST Collaboration)J. Urol.202120656857610.1097/JU.000000000000178633881931 · doi ↗ · pubmed ↗
- 8Douglawi A. Ghoreifi A. Lee R. Yip W. Seyedian S.S.L. Ahmadi H. Cai J. Miranda G. Yu W. Bhanvadia S. Bladder Recurrence Following Diagnostic Ureteroscopy in Patients Undergoing Nephroureterectomy for Upper Tract Urothelial Cancer: Is Ureteral Access Sheath Protective?Urology 202216014214610.1016/j.urology.2021.11.02634929237 · doi ↗ · pubmed ↗
