pT classification, grade, and vascular invasion as prognostic indicators in urothelial carcinoma of the upper urinary tract

Abstract

Clinicopathologic features predictive of patient outcome in upper urinary tract urothelial carcinoma are not well defined. The aim of this study was to assess the role of pT classification, tumor grade, and vascular invasion in predicting metastasis-free survival. A total of 190 consecutive invasive upper urinary tract urothelial cancers operated between 01/1984 and 12/2004 were re-evaluated with respect to pT classification, tumor grade (according to the three-tiered WHO 1973 and the recent two-tiered grading system following the WHO/ISUP consensus classification), as well as presence of lymph and/or blood vessel invasion. Prognostic impact was analyzed using the Kaplan-Meier method and the Log-Rank test. For multivariate testing, a Cox's proportional hazards regression model was used. pT1 was present in 81 (43%), pT2 in 29 (15%), pT3 in 73 (38%), and pT4 in seven (4%) cases. There were 12 (6%) G1, 96 (51%) G2, and 82 (43%) G3 tumors or 84 (44%) low-grade and 106 (56%) high-grade tumors according to the two-tiered system. The presence of vascular invasion in 72/190 (38%) tumors was associated with high pT classification (Po0.001) and high tumor grade (Po0.001). Disease progression occurred in 39% of patients, with 5-and 10-year metastasis-free survival rates of 56 and 45%, respectively. On univariate analysis, all investigated parameters showed prognostic significance. The negative influence of vascular invasion on patient outcome was strikingly strong in high pT classification and high-grade cancers. On multivariate analysis, pT classification (Po0.001) and vascular invasion (Po0.001) proved to be independent prognostic factors, whereas tumor grade according to the two-tiered system missed statistical significance (P ¼ 0.06). In conclusion, pT classification and vascular invasion are independent prognostic factors with respect to metastasis-free survival and should be used to guide adjuvant therapy strategies in affected patients. Presence (or absence) of vascular invasion should be commented upon separately in the pathology report. Modern Pathology (2006Pathology ( ) 19, 272-279. doi:10.1038 Keywords: urothelial carcinoma; upper urinary tract; tumor classification; tumor grade; vascular invasion; prognosis A significant proportion of patients with upper urinary tract urothelial carcinoma (UC) eventually die of the disease due to unrecognized and untreated nodal or distant metastasis present at the time of surgery, indicating the importance of adequate adjuvant therapy strategies for patients at high risk of failure. Initial tumor stage and tumor grade have been documented as major prognostic factors. 1-25 However, validity of most studies is limited due to inclusion of noninvasive (pTa) cancer cases and/or small sample size. Thus, to the best of our knowledge, there are only two systematic studies involving more than 100 invasive cancer cases including both univariate and multivariate statistical analyses with respect to recurrence-free and disease-specific survival. 12,24 Moreover, the assessment of tumor gr...

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

“…Although several studies have identified LVI as a poor prognostic feature, only a few have controlled for possible confounding factors by using multivariate analyses. 4,8,12,23,24 In agreement with several single-center reports, our multiinstitutional study revealed that 25% of patients undergoing RNU for UTUC had histologically identifiable LVI. As previously reported in several cystectomy and RNU series, LVI was associated with advanced stage, grade, and LN status.…”

“…4,20,21 Unlike previous reports, however, we provide compelling data that the new 2-tiered tumor grading system is a powerful independent predictor of recurrence and death from UTUC. Largely depending on the stage of the primary tumor, 20-40 % of patients with UTUC are historically found to harbor LN metastases.…”

“…As previously reported in several cystectomy and RNU series, LVI was associated with advanced stage, grade, and LN status. 4,8,9,12,[23][24][25][26] Importantly, we found that LVI was also an independent predictor of relapse and death from UTUC. Several investigators have reported that the tumor growth pattern, as defined by Jimenez at al is an independent predictor of oncologic outcome in patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder.…”

“…[3][4][5][6][7] While, these reports have contributed greatly to the current knowledge of the natural history and the prognostic factors important in UTUC, conclusions have been limited by small patient numbers and inhomogeneity of the study populations, as related to diagnosis, patient selection, staging, pathologic evaluation, and treatment. Nonetheless, these series have uniformly established that a significant proportion of UTUC patients eventually die of their disease due to unrecognized systemic metastases present at the time of surgery, underscoring the importance of thoughtful integration of adjuvant or neoadjuvant therapy strategies for patients at high risk of disease relapse.…”

“…Whereas tumor stage and histologic grade are well established prognostic factors of outcome after RNU, the oncologic significance of other potentially relevant variables, such as tumor site, architecture, histologic tumor necrosis, lymphovascular invasion (LVI), and the presence of concomitant carcinoma-in situ (CIS), among others, has not been clearly established. 4,[8][9][10][11][12][13][14][15] Recognizing these limitations, we developed a comprehensive database incorporating the clinical and pathologic characteristics and outcomes of over 1300 patients treated with RNU for UTUC at 12 academic centers. Using this large international patient cohort, strict accrual criteria, and pathologic re-review of all slides, we sought to more clearly define the natural history, patterns of failure, and the impact of potential prognostic factors on relapse and survival after surgical management of UTUC.…”