Upper tract urothelial carcinoma (UTUC) is a relatively rare yet aggressive malignancy. While radical nephroureterectomy (RNU) remains the cornerstone treatment, UTUC has high local and metastatic relapse rates, leading to a dismal prognosis. To identify the clinicopathological factors associated with an increased risk of local and metastatic relapse in UTUC, we conducted a retrospective analysis of 133 consecutive UTUC patients who underwent RNU from 1998 to 2018. Patients lost to follow-up or with a history of bladder cancer were excluded from the study. The remaining 87 patients were categorized into two subgroups: those with tumor recurrence/relapse (40 cases) and those without recurrence/relapse (47 cases). Clinical and pathological characteristics were compared across the two groups. Multiple factors are associated with UTUC recurrence/relapse including larger tumor size, histology divergent differentiations/subtypes, high tumor grade, advanced pathologic T stage, positive margin, lymphovascular invasion (LVI), positive lymph node status, and preoperative hydronephrosis. Multivariate Cox regression analysis revealed that squamous differentiation predicted recurrence/relapse (p = 0.012), independent of tumor stage. Moreover, compared to the conventional histology type, UTUC with squamous differentiation had a significantly higher relapse rate (p = 0.0001) and poorer survival (p = 0.0039). This observation was further validated in invasive high-grade UTUC cases. Our findings suggest that many pathological factors contribute to UTUC recurrence/relapse, particularly, squamous differentiation may serve as an independent risk predictor for relapse and a potent prognosticator for adverse cancer-specific survival in UTUC patients. Recognizing and thoroughly assessing the pathological factors is essential for better oncologic management of UTUC.
Annals of diagnostic pathology. 2024 Jun 22 [Epub ahead of print]
Yong Zhang, Qingqing Wu, Joshua I Warrick, David J DeGraff, Jay D Raman, Hong Truong, Guoli Chen
Department of Pathology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America., Department of Pathology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America; Department of Urology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America., Department of Pathology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America; Department of Urology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America; Department of Biochemistry and Molecular Biology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America., Department of Urology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America., Department of Pathology, Penn State Health Hershey Medical Center, Penn State College of Medicine, Hershey, PA, United States of America. Electronic address: .