Does multidetector computed tomographic urography (MDCTU) T staging classification correspond with pathologic T staging in upper tract urothelial carcinoma?

PURPOSE: Multidetector computed tomographic urography (MDCTU) is not yet sufficient to be used in the clinical staging of upper tract urothelial carcinoma (UTUC). This study aimed to compare the diagnostic accuracy of MDCTU T stage classification and pathologic T staging for UTUC. METHODS: We retrospectively evaluated 125 patients with UTUC who underwent preoperative MDCTU. A single radiologist classified the MDCTU pattern of the tumors as either low or advanced T stage for localized or locally advanced tumors, respectively. The diagnostic values of MDCTU for locally advanced tumors and the kappa agreement between MDCTU and pathologic T stage were investigated. RESULTS: Among 85 pathologic low T stage (Ta-T2) tumors, 71 low T stage tumors were correctly detected by MDCTU, while 30 out of 40 advanced T stage (T3-T4) tumors were correctly diagnosed by MDCTU. MDCTU led to under-staging in 8% (10/125) tumors and over-staging in 11.2% (14/125) tumors. Therefore, the overall accuracy of MDCTU in the diagnosis of low and advanced T stage tumors was 80.8% (101/125 patients). The sensitivity for advanced T stage tumors was 75% (30/40), the specificity was 83.5% (71/85), and the positive and negative predictive values were 68.1% (30/44) and 87.6% (71/81), respectively. The kappa agreement value between the MDCTU T stage and pathologic T stage was 0.57 (95% confidence interval (CI) 0.42-0.72), which was statistically significant (P = 0.001). CONCLUSION: MDCTU T stage classification may be relatively accurate for the detection and staging of UTUC correspondence with a pathologic stage.

Outcomes of nonmetastatic micropapillary variant upper tract urothelial carcinoma.

PURPOSE: Micropapillary variant upper tract urothelial cancer (MP-UTUC) is a rare malignancy with little known regarding its clinical course and/or optimal treatment. In this case series, we describe patient characteristics, surgical treatment, oncologic outcomes, and response to perioperative chemotherapy. MATERIALS AND METHODS: We conducted a review to identify patients with MP-UTUC treated at our center between January 1994 and October 2017. Clinicopathologic data was obtained. Descriptive statistics, Kaplan-Meier analysis, Cox proportional hazards, and nearest neighbor matching were used to examine the cohort. RESULTS: Eighteen, (4.3%) of 416 patients were found to have MP-UTUC at our institution over a 23-year period. The majority of patients had ≥pT3 disease at the time of extirpative surgery (13/18, 72%) and one was identified as MP-UTUC prior to surgery. Seven patients received neoadjuvant chemotherapy and six patients received adjuvant chemotherapy. Median overall, cancer specific, and recurrence free survival were 3.29, 3.29, and 1.69 years, respectively for MP-UTUC. There was no survival difference between conventional UTUC and MP-UTUC when matched for age, stage, grade, lymphovascular invasion, and margins (HR 1.18, P = 0.567). No MP-UTUC patients receiving neoadjuvant and adjuvant chemotherapy had apparent pathologic down staging, and of those receiving adjuvant chemotherapy two-thirds died of disease within 2 years. CONCLUSIONS: MP-UTUC is a rare, and in most cases aggressive malignancy that commonly presents as locally advanced disease. In this case series, MP-UTUC does not appear to respond to perioperative chemotherapy as neoadjuvant and adjuvant chemotherapy did not result in apparent pathologic down staging and the majority of those receiving adjuvant chemotherapy died from MP-UTUC.

A new proposal to risk stratify urothelial carcinomas of the upper urinary tract (UTUCs) in a predefinitive treatment setting: low-risk versus high-risk UTUCs.

Risk stratification of upper tract urothelial carcinoma (UTUC) patients and tumours is crucial for highlighting that an alternative to radical extirpative surgery now exists and should be considered for all patients who qualify as having low-risk UTUC.

Subclassification of upper urinary tract urothelial carcinoma by the neutrophil-to-lymphocyte ratio (NLR) improves prediction of oncological outcome.

OBJECTIVE: To examine the potential role of the neutrophil-to-lymphocyte ratio (NLR) for subclassification of localised upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS: From 2004 to 2010, 234 patients with localised UUT-UC underwent radical nephroureterectomy (RNU). NLRs were only obtained under afebrile conditions before RNU. Patients that underwent neoadjuvant or adjuvant chemotherapy were excluded. The prognostic impact of the NLR was assessed using the log-rank test and multivariate analyses. RESULTS: Only advanced pathological stage (>T2) and a NLR of >3 were independently associated with metastasis (P < 0.001 and P = 0.02, respectively) and cancer-specific mortality (P = 0.002 and P = 0.006, respectively). The use of a NLR of >3 further identified a poor prognostic group, especially in patients with T3 UUT-UC for metastasis-free survival and cancer-specific survival (log-rank test, both P < 0.001). CONCLUSIONS: For localised UUT-UC, pathological stage and preoperative NLR independently predict systemic recurrence and cancer-specific death after RNU. Using the NLR for subclassification of T3 UUT-UC seems to further identify a poor prognostic group and may help with clinical decisions about treatment intervention in clinical practice.

Does preoperative symptom classification impact prognosis in patients with clinically localized upper-tract urothelial carcinoma managed by radical nephroureterectomy?

OBJECTIVES: To evaluate if preoperative symptom classification could refine prediction of outcomes for patients with clinically localized upper-tract urothelial carcinoma (UTUC) managed by radical nephroureterectomy (RNU). METHODS: Data on 654 patients with localized UTUC who underwent RNU were reviewed. Preoperative symptoms were classified as incidental (S1), local (S2), and systemic (S3). Clinical and pathologic data were compared between the cohorts. Kaplan-Meier analyses and Cox proportional hazard modeling were used to determine recurrence-free and cancer-specific survival amongst the symptom cohorts. RESULTS: Symptom classification was S1 in 213 (33%) patients, S2 in 402 (61%), and S3 in 39 (6%). S3 symptoms were associated with advanced pathology, including higher stage, grade, and lymph node (LN) positivity. Five and 10-year recurrence-free and cancer-specific survival estimates were similar for patients with S1 and S2 symptoms (P = 0.75 and 0.58, respectively), but was worse for patients with S3 symptoms (P < 0.001 for both). On multivariate analysis adjusting for final pathologic stage, grade, and LN status, S3 symptoms were not an independent predictor of recurrence (HR 1.44, P = 0.19) or death due to disease (HR 1.66, P = 0.07). Addition of symptom classification, however, increased the accuracy of a model consisting of stage, grade, and LNs for prediction of recurrence-free and cancer-specific survival by 1.4% and 1.3%, respectively (P < 0.001 for both). CONCLUSIONS: Local symptoms do not confer worse prognosis compared with patients with incidentally detected UTUC. However, systemic symptoms are associated with worse outcomes despite apparently effective RNU. Patients with systemic symptoms may harbor micrometastatic disease and could potentially benefit from a more rigorous metastatic evaluation or perioperative chemotherapy regimens.

Neoplasms of the upper urinary tract: a review with focus on urothelial carcinoma of the pelvicalyceal system and aspects related to its diagnosis and reporting.

Tumors of the renal pelvis account for approximately 7% to 8% of all renal malignancies, greater than 90% of these are of urothelial (transitional cell) origin. These tumors more typically occur in the sixth to eight decade with a slight male preponderance. Varying risk factors for urothelial carcinomas of the upper tract are recognized including environmental and occupational hazards, chemotherapeutic exposure, and previous history of urinary bladder or ureteral carcinomas. Tumor multifocality is frequent and additional tumors may arise in the ureter, bladder, or on the contralateral side. The histopathologic nuances presented by urothelial carcinoma in this region are generally similar to those in the urinary bladder. Though the World Health Organization 2004/International Society of Urological Pathology system used in the bladder is customarily also employed for grading of urothelial tumors of this region, its prognostic significance at this site is not entirely clear as most tumors are treated with nephroureterectomy irrespective of the grade of the tumor. Histologic grade may be an independent prognostic factor in papillary pT1 tumors; however, most pT2 and higher stage tumors tend to be nonpapillary and of higher grade. Despite advances in treatment modalities with sophisticated endoscopic techniques, tumor stage remains the most important prognostic factor. There are several confounding issues related to staging such as the variable presence and thickness of subepithelial connective tissue and muscularis in the renal calyces, renal pelvis, and the ureter; intratubular pagetoid cancer spread (pTis vs. pT3); and assessing invasion in papillary neoplasms with endophytic or inverted growth. Careful gross examination with adequate sampling and understanding the microanatomy of the pelvicalyceal wall are crucial for accurate stage assignment. Poor fixation of large friable tumors and processing artifacts may compound difficulties in accurate staging. This review focuses on urothelial carcinoma of the upper tract highlighting issues related to its diagnosis, staging, and reporting.

Molecular genetic findings in two cases of sarcomatoid carcinoma of the ureter: evidence for evolution from a common pluripotent progenitor cell?

The current World Health Organization classification recommends the usage of the term sarcomatoid carcinoma (SC) for all biphasic malignant neoplasms of the urinary tract exhibiting morphologic and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. While most SC have been described in the urinary bladder, ureteral SC are extremely rare tumors. Here, we report on the clinical, morphological, and molecular biological findings of two cases in this unusual location. The genetic alterations investigated by comparative genomic hybridization in the epithelial and the mesenchymal component of both cases showed considerable but not complete overlap. Moreover, in spite of many morphological differences between the two cases, both cases shared some genetic gains and losses. Our findings are compatible with the concept that SC originates from a common pluripotent progenitor cell with a potential for epithelial and mesenchymal differentiation.

Muscle invasive bladder tumor 18 months after laparoscopic radical nephrourectomy / Tumor vesical infiltrante 18 meses después de nefrectomía radical laparoscópica

Objective: The management of the distal ureter and bladder cuff is an important issue related to laparoscopic nephroureterectomy, because of the fear that local and bladder recurrences could be induced by an inadequate manipulation of the specimen. We present a case of muscle invasive bladder tumor that appeared 18 months after laparoscopic radical nephroureterectomy. Methods/Results: A 42 year-old woman with multifocal grade 3 pT3, right kidney urothelial carcinoma, treated by laparoscopic radical nephroureterectomy with early clipping of the distal ureter, transurethral detachment of the intramural ureter, and no bladder closure, presented with an invasive bladder recurrence after 18 months of follow-up. Conclussions: There is no a definitive answer to the question of what is the best and safest way of treating the intramural ureter to prevent local and bladder recurrences. However, early clip occlusion of the ureter to avoid downstream cell seeding during kidney manipulation, and an open approach to the distal ureter in case of concomitant distal ureter or bladder tumor is recommended (AU)

Objetivo: El manejo del uréter distal y del manguito vesical es uno de los aspectos más importantes y discutidos de la nefroureterectomía laparoscópica por tumor de urotelio, porque existe el temor de que una manipulación indecuada de la pieza pueda inducir una recidiva vesical o local. Describimos un caso de tumor vesical infiltrante aparecido a los 18 meses de una nefroureterectomía radical laparoscópica. Método/Resultado: Una mujer de 42 años con carcinoma de urotelio multifocal de la pelvis y cáliz inferior del riñón derecho, grado 3, pT3, que fue tratado mediante desinserción transuretral del uréter intramural y nefroureterectomía radical con clipado precoz del uréter distal, presentó una recidiva de tumor vesical infiltrante a los 18 meses de seguimiento, de curso fatal en poco tiempo. Conclusión: Aún no hay una respuesta definitiva a la cuestión de cuál es el mejor y más seguro modo de tratar el uréter intramural para prevenir una recidiva local o vesical, después de nefroureterectomia laparoscópica por tumor de urotelio. Se recomienda un oclusión precoz del uréter para evitar una potencial siembra de células durante la manipulación del riñón, y elegir un acceso abierto al uréter distal en caso de tumor de uréter pelviano o de tumor vesical concomitante (AU)

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

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 (P<0.001) and high tumor grade (P<0.001). 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 (P<0.001) and vascular invasion (P<0.001) proved to be independent prognostic factors, whereas tumor grade according to the two-tiered system missed statistical significance (P=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.

Urothelial carcinoma of the upper urinary tract: comparison between the WHO/ISUP 1998 consensus classification and WHO 1999 classification system.

OBJECTIVES: To compare the usefulness of World Health Organization (WHO)/International Society of Urological Pathologists 1998 consensus classification with the WHO 1999 classification in a large series of urothelial tumors of the upper urinary tract. Only a few bladder tumor studies have compared these systems. METHODS: A clinical and histopathologic review was performed of all patients diagnosed in western Sweden between 1971 and 1998 with renal pelvic or ureteral carcinoma. We selected 555 surgically treated patients who all had a urothelial tumor on review of the pathologic findings and no bladder tumor before diagnosis of the upper tract tumor. The median follow-up was 52 months. Disease-specific survival was calculated using Kaplan-Meier estimates. RESULTS: A total of 349 patients had Stage pTa, pT1, or pT2 tumor, with a 5-year disease-specific survival rate of 95%, 80%, and 79%, respectively. No significant difference was found in the prognosis among papillary urothelial neoplasm of low malignant potential and low-grade and high-grade tumors of the same stage. Nor was a difference found among papillary urothelial neoplasm of low malignant potential and grade 1, 2, and 3 tumors. Of the 349 patients, 171, all with high-grade Stage pT3 tumors, had a 35% disease-specific survival rate. Of these tumors, 38 were grade 2 and 133 were grade 3, with a survival rate of 49% and 25%, respectively (P <0.0037). All 35 pT4 tumors were high grade, and no patient survived past 30 months. CONCLUSIONS: Tumor stage was a very strong predictor of prognosis in this series of patients treated with open surgery. The tumor grade had little additional prognostic value, although a small advantage was found for the WHO 1999 classification, but only for high-grade, Stage pT3 tumors.

EAU guidelines on diagnosis and treatment of upper urinary tract transitional cell carcinoma.

OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of upper urinary tract transitional cell carcinoma (UUTT) patients were established. Criteria for recommendations are based of level 2 only, as large randomised clinical trials have not been performed in this type of disease. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. RESULTS: TNM classification 2002 is recommended. Recommendations are developed for diagnosis, radical and conservative treatment and for local chemo-immunotherapy. Prognostic factors are defined. Recommendations for follow-up after different types of treatment are given.

[Pathologic classification of upper urinary tract tumors]. / Clasificación anatomopatológica de los tumores del urotelio superior.

OBJECTIVES: To do an update on the upper urinary tract tumors classification systems. METHODS/RESULTS: Bibliography review of the various classification systems appeared over the last years, comparing them and reviewing their associated problems. CONCLUSIONS: Current systematization advocated by WHO and ISUP are the most adequate for patient stratification. However, there are problems for coupling tumors with characteristics in the limit between some of their categories, so that we consider it will be convenient to review them.

Urothelial neoplasms of the kidney and ureter. An epidemiologic, pathologic, and clinical review.

Urothelial neoplasms occur with varying frequency at different sites along the urothelial tract. Approximately 5% of urothelial neoplasms occur in the kidneys and ureters, while the majority of these tumors occur in the urinary bladder. Consequently, urothelial disease of the bladder has been evaluated to a greater extent than urothelial tumors elsewhere, and many of the features of bladder urothelial neoplasms have been applied to these tumors at other sites. While the classification of urothelial neoplasms is the same for tumors in the bladder, kidney, and ureter, there are some features of urothelial neoplasms of the kidney and ureter that are unique to these sites. An epidemiologic, pathologic, and clinical review of urothelial neoplasms of the kidney and ureter is presented.

[Tumors of the upper excretory tract]. / Tumeurs de la voie excrétrice supérieure.

Most tumors of the upper urinary tract are epithelial tumors from transitional cell origin. They are more frequent in the renal pelvis than in the ureter. They may be single or multiple and rarely bilateral. Gross hematuria is the most common presenting form. Computed tomography is useful both in the diagnosis and staging and is much more contributive than intravenous pyelography. Nephroureterectomy with a bladder cuff is the standard treatment for upper tract tumors. In selected cases are low grade and low stage tumors, conservative surgery can be discussed with similar longterm results than radical surgery.

[Classification and prognosis of supravesical urothelioma with the new TNM classification]. / Gliederung und Prognose der supravesikalen Urotheliome nach der neuen TNM-Klassifikation.

We report on 149 patients with supravesical urothelioma (transitional cell carcinoma of the upper urinary tract) treated in our hospital during the years 1967-1991. The introduction shows the distribution of sex and age as well as the localization of the tumor. Main topic of this paper is a new definition of the clinical pathology of supravesical urothelioma by means of the TNM classification published 1987. Based on the pathological pioneer work of P. Hermanek our results are as follows: during the first diagnosis pT3 predominates with 30.2%, followed by pT1 with 25.5% and pTa, pT1 and pT4 with a relatively low incidence. G2 predominates with 47.7%; G1 and G3 have almost the same frequency. The G/pT ratio shows a decreasing linearity for G1 from pTa to pT4; for G2 there is equivalence of pT1-pT3; and pTa and pT4 are relatively rare. With respect to G3, pT3 predominates with 51%, followed by pT4, pT1 and finally pTa with zero frequency. The G/M ratio shows M0 only for G1, 10% M positive for G2 and 15% M positive for G3. The 10-year survival rate for patients with R0 resection and stage pTa is 64% and for pT1-pT4, 33-36%. The 10-year survival rate for patients with G1 tumor is 51%, and that for G3 tumors 30%. Multicentric occurrence and carcinoma in situ have no prognostic significance in our sample. As is well known, papillary growth has a better prognosis than solid infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary malignant tumor of the ureter. Presentation of a case]. / Tumor maligno del uréter primario. Presentación de un caso.

Herein we report a case of malignant primary tumor of the ureter that had been seen and treated in the Department of Urology of Hospital Docente Clinico Quirurgico "10 de Octubre", in Havana, Cuba. The incidence, possible etiology, classification, forms of presentation, diagnosis, treatment and prognosis of this disease entity are discussed. The national and the world literature are reviewed.