Sessile Tumor Architecture Research Articles

Prognostic factors for upper urinary tract urothelial carcinoma

Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, which means there are little evidence-based data available to guide clinical decision-making. Although diagnosis and treatment of UTUC have improved significantly over the last 5 years, accurate risk stratification remains a challenge owing to the difficulty of clinical staging. A number of potential prognostic factors have been identified, encompassing clinical characteristics, pathological factors and molecular markers. Tumor stage and lymph node status are the most important predictors of survival in patients with UTUC. Preoperative evaluation for hydronephrosis can identify patients at risk of non-organ-confined disease. In the subgroup of patients with stage ≥pT2 disease, a longer interval between diagnosis and radical nephroureterectomy is associated with a higher risk of disease recurrence and cancer-specific mortality. Extensive tumor necrosis, sessile tumor architecture and lymphovascular invasion are independent predictors of clinical outcomes for patients with UTUC treated with radical nephroureterectomy. The incorporation of such prognosticators into clinical prediction models might help to guide decision-making with regard to timing of surveillance, type of treatment, performance of lymphadenectomy, and consideration of neoadjuvant or adjuvant systemic therapies.

Macroscopic sessile tumor architecture is a pathologic feature of biologically aggressive upper tract urothelial carcinoma

ObjectiveMacroscopic sessile tumor architecture was associated with adverse outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Before inclusion in daily clinical decision-making, the prognostic value of tumor architecture needs to be validated in an independent, external dataset. We tested whether macroscopic tumor architecture improves outcome prediction in an international cohort of patients. Material and methodsWe retrospectively studied 754 patients treated with RNU for UTUC without neoadjuvant chemotherapy at 9 centers located in Asia, Canada, and Europe. Tumor architecture was macroscopically categorized as either papillary or sessile. Univariable and multivariable Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. ResultsMacroscopic sessile architecture was present in 20% of the patients. Its prevalence increased with advancing pathologic stage and it was significantly associated with established features of biologically aggressive UTUC, such as tumor grade, lymph node metastasis, lymphovascular invasion, and concomitant CIS (all P values < 0.02). The median follow-up for patients who were alive at last follow-up was 40 months (IQR: 18–75 months, range: 1–271 months). Two-year RFS and CSS for tumors with papillary architecture were 85% and 90%, compared with 58% and 66% for those with macroscopic sessile architecture, respectively (P values < 0.0001). On multivariable Cox regression analyses, macroscopic sessile architecture was an independent predictor of both RFS (hazard ratio {HR}: 1.5; P = 0.036) and CSS (HR: 1.5; P = 0.03). ConclusionWe confirmed the independent prognostic value of macroscopic tumor architecture in a large, independent, multicenter UTUC cohort. It should be reported in every pathology report and included in post-RNU predictive models in order to refine current clinical decision making regarding follow-up protocol and adjuvant therapy.

Association of Tumor Necrosis With Pathological Features and Clinical Outcome in 754 Patients Undergoing Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An International Validation Study

Tumor necrosis is associated with a poor oncological outcome in patients with upper tract urothelial carcinoma and other malignancies. We validated the association of tumor necrosis with pathological features and clinical outcomes in a large international cohort of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. This retrospective study included 754 patients treated with radical nephroureterectomy at a total of 9 centers. Tumor necrosis was scored as greater than 10% of tumor area based on microscopic evaluation. Tumor necrosis was present in 165 specimens (21.9%). The prevalence of tumor necrosis increased with advancing pathological stage, including 7%, 10.6% and 50% for T1, T2 and T3-4, respectively (p <0.001). Tumor necrosis was associated with features of aggressive upper tract urothelial carcinoma, such as high grade, lymph node metastasis, lymphovascular invasion, sessile tumor architecture and concomitant carcinoma in situ (p <0.002). Median followup in censored patients was 40 months (IQR 18 to 75). On univariate Cox regression analysis tumor necrosis was significantly associated with disease recurrence and cancer specific mortality (HR 2.4 and 2.7, p <0.001). However, on multivariate Cox regression analysis including patient age, stage, grade, lymph node status, lymphovascular invasion and adjuvant chemotherapy tumor necrosis was not associated with disease recurrence (HR 1.1, p = 0.49) or cancer specific mortality (HR 1.1, p = 0.51). Excluding 63 patients who received adjuvant chemotherapy and/or 49 with positive lymph nodes did not substantially change these results. In this large, multicenter international study tumor necrosis was associated with pathological features of biologically aggressive upper tract urothelial carcinoma. However, tumor necrosis was not an independent predictor of clinical outcomes.

Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high‐risk upper tract transitional cell carcinoma

The authors evaluated the incidence of pathologic downstaging and complete remission (CR) in patients with high-grade ureteral and renal pelvic transitional cell carcinoma (TCC) (upper tract TCC) who received neoadjuvant chemotherapy followed by surgery. The study group comprised patients with biopsy-demonstrated, high-grade disease who received neoadjuvant chemotherapy followed by nephrouterectomy from 2004 to 2008, during which time patients uniformly were considered for neoadjuvant chemotherapy. The control group comprised patients with biopsy-demonstrated, high-grade disease who underwent initial nephroureterectomy from 1993 to 2004, when patients uniformly underwent initial surgery. Multiple clinical and pathologic features were evaluated, and the primary endpoint was pathologic tumor classification. One hundred seven patients in the control group underwent initial surgery, and 43 patients in the study group received neoadjuvant chemotherapy. Baseline demographics were similar between the groups except for a higher rate of sessile tumor architecture in the study group (72.1% vs 49.5%; P = .018). There was significant downstaging in study group patients compared with the historic control group (P = .004). The incidence of tumors classified as pathologic T2 (pT2) or as pT3 or higher was significantly lower in the study group (pT2, 65.4% vs 48.8%; P = .043; pT3 or higher, 47.7% vs 27.9%; P = .029). Fourteen percent of patients who received neoadjuvant chemotherapy had a pathologic CR. Neoadjuvant chemotherapy was associated with a 14% CR rate and a significant rate of downstaging. While longer follow-up is awaited for survival data to mature, the current data provide justification for the sustained support of trials using this strategy.

Lymphovascular Invasion Predicts Clinical Outcomes in Patients With Node-Negative Upper Tract Urothelial Carcinoma

To assess the association of lymphovascular invasion (LVI) with cancer recurrence and survival in a large international series of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). Data were collected on 1,453 patients treated with RNU at 13 academic centers and combined into a relational database. Pathologic slides were rereviewed by genitourinary pathologists according to strict criteria. LVI was defined as presence of tumor cells within an endothelium-lined space. LVI was observed in 349 patients (24%). Proportion of LVI increased with advancing tumor stage, high tumor grade, presence of tumor necrosis, sessile tumor architecture, and presence of lymph node metastasis (all P < .001). LVI was an independent predictor of disease recurrence and survival (P < .001 for both). Addition of LVI to the base model (comprising pathologic stage, grade, and lymph node status) marginally improved its predictive accuracy for both disease recurrence and survival (1.1%, P = .03; and 1.7%, P < .001, respectively). In patients with negative lymph nodes and those in whom a lymphadenectomy was not performed (n = 1,313), addition of LVI to the base model improved the predictive accuracy of the base model for both disease recurrence and survival by 3% (P < .001 for both). In contrast, LVI was not associated with disease recurrence or survival in node-positive patients (n = 140). LVI was an independent predictor of clinical outcomes in nonmetastatic patients who underwent RNU for UTUC. Assessment of LVI may help identify patients who could benefit from multimodal therapy after RNU. After confirmation, LVI should be included in staging of UTUC.

Lymphovascular Invasion and Pathologic Tumor Stage Are Significant Outcome Predictors for Patients With Upper Tract Urothelial Carcinoma

To determine the predictors of urothelial recurrence, distant metastases, and disease-specific survival (DSS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The records of 136 patients who underwent RNU in our department between 1983 and 2004 were reviewed. The study population consisted of 116 patients from whom tumor specimens were available for re-evaluation, focusing on pathologic tumor (pT) stage, grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and the presence of significant tumor necrosis. Univariate and multivariate analyses were performed. The median follow-up was 38 months (range: 1-193 months). At actual follow-up, 63 patients (56%) were alive and disease-free. Concomitant CIS independently predicted urothelial recurrence (P = .008). Five-year actual DSS by pT stage was 100% for pTa and pTis, 95% for pT1, 70% for pT2, 54% for pT3, and 14% for pT4 tumors. Disease-specific mortality occurred in 32 patients (28%). A sessile tumor architecture, pT stage, grade, the presence of LVI (all P < .001), a positive surgical margin (P = .012), tumor necrosis (P = .004), and lymph node metastases (P = .034) were significantly associated with reduced DSS on univariate analysis. Multivariate analysis revealed the presence of LVI (P < .001) and pT stage (P = .023) as independent predictors for reduced DSS. RNU provides adequate local control and long-term DSS in patients with localized UTUC. LVI and pT stage are independent predictors for reduced DSS and can be used for the identification of patients who are likely to benefit from adjuvant therapies.