Medium-term follow up of active surveillance for early prostate cancer at a non-academic institution.

OBJECTIVES: To report oncological outcomes of active surveillance (AS) at a single non-academic institution adopting the standardised Prostate Cancer Research International Active Surveillance (PRIAS) protocol. PATIENTS AND METHODS: Competing risk analyses estimated the incidence of overall mortality, metastases, conversion to treatment, and grade reclassification. The incidence of reclassification and adverse pathological findings at radical prostatectomy were compared between patients fulfilling all PRIAS inclusion criteria vs those not fulfilling at least one. RESULTS: We analysed 341 men with Grade Group 1 prostate cancer (PCa) followed on AS between 2010 and 2022. There were no PCa deaths, two patients developed distant metastases and were alive at the end of the study period. The 10-year cumulative incidence of metastases was 1.9% (95% confidence interval [CI] 0.33-6.4%). A total of 111 men were reclassified, and 127 underwent definitive treatment. Men not fulfilling at least one PRIAS inclusion criteria (n = 43) had a higher incidence of reclassification (subdistribution hazards ratio 1.73, 95% CI 1.07-2.81; P = 0.03), but similar rates of adverse pathological findings at radical prostatectomy. CONCLUSION: Metastases in men on AS at a non-academic institution are as rare as those reported in established international cohorts. Men followed without stringent inclusion criteria should be counselled about the higher incidence of reclassification and reassured they can expect rates of adverse pathological findings comparable to those fulfilling all criteria. Therefore, AS should be proposed to all men with low-grade PCa regardless of whether they are followed at academic institutions or smaller community hospitals.

The impact of histological variants on outcomes after open radical cystectomy for muscle-invasive urothelial bladder cancer: results from a single tertiary referral centre.

OBJECTIVES: To evaluate the impact of histological variants on oncological outcomes of patients with muscle-invasive bladder cancer treated with open radical cystectomy and furthermore to determine any association between survival and each histotype of bladder cancer. MATERIALS AND METHODS: Data from 525 consecutive patients with muscle-invasive bladder cancer treated with radical cystectomy between January 2008 and May 2019 were collected retrospectively. The Kaplan-Meier curves and multivariable analysis addressed the role of histological variants in recurrence, cancer-specific and overall mortality between all subgroups. RESULTS: Of 525 patients, 131 (25.0%) showed a histological variant at radical cystectomy. With a median follow-up of 31 months, 209 (39.8%) recurrences, 184 (35.0%) cancer-related deaths and 260 (49.5%) overall deaths were reported. The presence of histological variant was associated with advanced tumour stage, the presence of concomitant carcinoma in situ, lymph node metastasis, lymphovascular invasion and positive surgical margins compared to pure urothelial bladder cancer (all p values < .008) and resulted as an independent risk factor for cancer-specific mortality (p = 0.001). Patients with a histological variant were at significantly higher risk for recurrence, cancer-specific mortality and overall mortality (all p values ≤ .001). Micropapillary, sarcomatoid or small cell differentiation was associated with reduced survival. CONCLUSION: The presence of histological variants at radical cystectomy seems to be weakly associated with reduced survival compared to pure urothelial bladder cancer paired for pathologic stage. The association of histological variants with advanced and biologically aggressive tumours suggests the need for attention on the overall management of these patients, in particular for micropapillary, sarcomatoid and small cell differentiation.

Impact of Resection Technique on Perioperative Outcomes and Surgical Margins after Partial Nephrectomy for Localized Renal Masses: A Prospective Multicenter Study.

PURPOSE: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury). MATERIALS AND METHODS: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement. RESULTS: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement. CONCLUSIONS: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

Increased Use of Blood Transfusions to Manage Urological Conditions during the COVID-19 Pandemic.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an extensive reorganization of the healthcare system in Italy, with significant deferment of the treatment of urology patients. We aimed to assess the impact of deferred treatment during the SARS-CoV-2 pandemic on the need for blood transfusions in 3 Italian urology departments. METHODS: We reviewed hospital chart data on blood transfusions at the urology units of 3 academic centers in the north of Italy from March to April 2020. Data were compared with values from the same time frame in 2019 (March to April 2019). RESULTS: We observed significant reductions of the number of patients admitted to the urology units from March to April 2020 (373 vs. 119) and the number of performed surgeries (242 vs. 938) compared to 2019. Though, the number of transfused blood units was comparable between the 2 years (182 vs. 252), we found a greater mean number of blood units transfused per admission in 2020 (0.49 vs. 0.22; p < 0.0001). As a whole, the transfusion rate for hematuria was higher in 2020 than in 2019 (36 vs. 7.9%; p < 0.0001). DISCUSSION/CONCLUSION: The observed increased number of blood transfusions needed throughout the SARS-CoV-2 era could have had a negative impact on both patients and the healthcare system. It is possible to speculate that this is the consequence of a delayed diagnosis and deferred treatment of acute conditions.

Diagnostic accuracy of multiparametric magnetic resonance imaging combined with clinical parameters in the detection of clinically significant prostate cancer: A novel diagnostic model.

OBJECTIVES: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging in the detection of prostate cancer, according to Prostate Imaging Reporting and Data System, and the usefulness of combining clinical parameters to improve patients' risk assessment. METHODS: Overall, 201 patients underwent multiparametric magnetic resonance imaging investigation with a 3-T magnet and a 32-channel body coil based on triplanar high-resolution T2-weighted, diffusion-weighted and T1-weighted dynamic contrast-enhanced imaging before, during and after intravenous administration of paramagnetic contrast agent. Random transrectal ultrasound-guided biopsy was carried out for all eligible patients. If a Prostate Imaging Reporting and Data System ≥3 lesion was present, a targeted biopsy with magnetic resonance imaging-transrectal ultrasound fusion-guided system was carried out. RESULTS: Sensitivity, specificity, positive predictive value and negative predictive value of Prostate Imaging Reporting and Data System ≥3 lesions for the detection of prostate cancer were 65.1%, 54.9%, 43.1% and 75.0% respectively, with an accuracy of 64.2% (55.1-72.7%). At uni- and multivariate analysis, age ≥70 years and prostate-specific antigen density ≥0.15 ng/mL/mL were significantly associated with prostate cancer. A new risk model named "modified Prostate Imaging Reporting and Data System" was created considering age and prostate-specific antigen density in addition to the Prostate Imaging Reporting and Data System score showing an improved correlation with prostate cancer compared with the Prostate Imaging Reporting and Data System alone (area under curve 71.4%, 95% confidence interval 62.2-80.5 vs area under curve 62.6%, 95% confidence interval 52.1-73; P ≤ 0.0001). CONCLUSIONS: The accuracy of Prostate Imaging Reporting and Data System alone in the diagnosis of prostate cancer might be suboptimal, whereas a novel risk model based on the combination of multiparametric magnetic resonance imaging data with clinical parameters could offer higher discrimination and improve the ability of diagnosing clinically significant disease.

Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study.

PURPOSE: To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05. RESULTS: 348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS. CONCLUSIONS: BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.

Postoperative Nomogram for Relapse-Free Survival in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: We developed a prognostic nomogram for patients with high grade urothelial carcinoma of the upper urinary tract after extirpative surgery. MATERIALS AND METHODS: Clinical data were available for 2,926 patients diagnosed with high grade urothelial carcinoma of the upper urinary tract who underwent extirpative surgery. Cox proportional hazard regression models identified independent prognosticators of relapse in the development cohort (838). A backward step-down selection process was applied to achieve the most informative nomogram with the least number of variables. The L2-regularized logistic regression was applied to generate the novel nomogram. Harrell's concordance indices were calculated to estimate the discriminative accuracy of the model. Internal validation processes were performed using bootstrapping, random sampling, tenfold cross-validation, LOOCV, Brier score, information score and F1 score. External validation was performed on an external cohort (2,088). Decision tree analysis was used to develop a risk classification model. Kaplan-Meier curves were applied to estimate the relapse rate for each category. RESULTS: Overall 35.3% and 30.7% of patients experienced relapse in the development and external validation cohort. The final nomogram included age, pT stage, pN stage and architecture. It achieved a discriminative accuracy of 0.71 and 0.76, and the AUC was 0.78 and 0.77 in the development and external validation cohort, respectively. Rigorous testing showed constant results. The 5-year relapse-free survival rates were 88.6%, 68.1%, 40.2% and 12.5% for the patients with low risk, intermediate risk, high risk and very high risk disease, respectively. CONCLUSIONS: The current nomogram, consisting of only 4 variables, shows high prognostic accuracy and risk stratification for patients with high grade urothelial carcinoma of the upper urinary tract following extirpative surgery, thereby adding meaningful information for clinical decision making.

Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. RESULTS: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). CONCLUSIONS: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.

Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract.

PURPOSE: We validate the independent predictive value of Ki-67 in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: A total of 475 patients from the international Upper Tract Urothelial Carcinoma Collaboration who underwent extirpative surgery for high grade upper tract urothelial carcinoma were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray formed from this patient cohort. Ki-67 expression was assessed in a semiquantitative fashion and considered over expressed at a cutoff of 20%. Multivariate analyses were performed to assess independent predictors of oncologic outcomes and Harrell's C indices were calculated for predictive models. RESULTS: The median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was over expressed in 25.9% of patients. Ki-67 over expression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ and regional lymph node metastases. On Kaplan-Meier analyses over expressed Ki-67 was associated with worse recurrence-free survival (HR 12.6, p <0.001) and cancer specific survival (HR 15.8, p <0.001). On multivariate analysis Ki-67 was an independent predictor of recurrence-free survival (HR 1.6, 95% CI 1.07-2.30, p=0.021) and cancer specific survival (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved Harrell's C index from 0.66 to 0.70 (p <0.0001) for recurrence-free survival as well as cancer specific survival in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for recurrence-free survival and 0.81 to 0.83 (p=0.005) for cancer specific survival in our postoperative model. CONCLUSIONS: Ki-67 was validated as an independent predictor of recurrence-free survival and cancer specific survival in patients treated with extirpative surgery for high grade upper tract urothelial carcinoma in a large, multi-institutional cohort.

TALL score for prediction of oncological outcomes after radical nephroureterectomy for high-grade upper tract urothelial carcinoma.

PURPOSE: We created a prognostic tool for the prediction of oncologic outcomes after radical nephroureterectomy (RNU) for high-grade non-metastatic upper tract urothelial carcinoma (UTUC). METHODS: UTUC collaboration was utilized to include 586 patients who underwent RNU for non-metastatic high-grade UTUC. Survival outcomes were compared according to a score defined based on the sum of the independent prognostic variables. RESULTS: The study included 382 males with a median age 70 years (range 28-97). Independent prognostic factors included: T (t stage), A (architecture), LVI (lympho-vascular invasion) and L (lymphadenectomy). TALL score (1-7) was the sum of T (≤T1 = 1, T2 = 2, T3 = 3 and T4 = 4), A (papillary = 0 and sessile = 1), LVI (absent = 0 and present = 1) and L (lymphadenectomy = 0 and no lymphadenectomy = 1). Five-year disease-free survival (DFS) and cancer-specific survival (CSS) were stratified into four risk categories according to the TALL score: low (TALL 0-2; 86 % DFS and 90 % CSS), intermediate (TALL = 3; 71 % DFS and 75 % CSS), high (TALL = 4; 57 % DFS and 58 % CSS) and very high risk (TALL ≥ 5; 34 % DFS and 38 % CSS) using Kaplan-Meier survival analyses. TALL score was externally validated in a single-center cohort of 85 UTUC patients. CONCLUSIONS: We developed a multivariable prognostic tool for the prediction of oncological outcomes after RNU for high-grade UTUC. The score can be used for patient counseling, selection for adjuvant systemic therapies and design of clinical trials.

Extent of lymph node dissection at nephrectomy affects cancer-specific survival and metastatic progression in specific sub-categories of patients with renal cell carcinoma (RCC).

OBJECTIVE: To test whether the number of lymph nodes removed affects cancer-specific survival (CSS) or metastatic progression-free survival (MPFS) in different renal cell carcinoma (RCC) scenarios. METHODS: We used Cox regression analyses to analyse the effect of the number of lymph nodes removed on CSS and MPFS in 1983 patients with RCC treated with nephrectomy. To adjust for possible clinical and surgical selection bias, analyses were further adjusted for number of positive nodes, presence of metastases, age, performance status, T stage, tumour size and grade. RESULTS: The prevalence of lymph node invasion was 6.1%. The mean follow-up period was 83.3 months. Multivariable analyses showed that the number of nodes removed had an independent, protective effect on CSS in patients with pT2a-pT2b or pT3c-pT4 RCC (hazard ratio [HR] 0.91, P = 0.008 and HR 0.89, P < 0.001, respectively), in patients with bulky tumours (tumour size >10 cm, HR 0.97, P = 0.03) or when sarcomatoid features were found (HR 0.81, P = 0.006). The removal of each additional lymph node was associated with a 3-19% increase in CSS. When considering MPFS as an endpoint, the number of nodes removed had an independent, protective effect in the same patient categories. CONCLUSIONS: When clinically indicated, the number of nodes removed affects CSS and MPFS in specific sub-categories of patients with RCC.

Staging lymphadenectomy in renal cell carcinoma must be extended: a sensitivity curve analysis.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In renal cell carcinoma the role of lymphadenectomy (LND) is still controversial. Moreover, no firm consensus exists regarding the minimum number of lymph nodes that should be removed to obtain a satisfactory staging LND at the time of surgery. Our findings demonstrate that, when clinically indicated, staging LND in renal cell carcinoma should be extended. The removal of 15 lymph nodes might represent the lowest threshold to define a staging LND as adequate. More extended LND should be pursued if unfavourable clinical and pathological characteristics are evident at diagnosis and/or during surgery. OBJECTIVE: To investigate the staging of lymphadenectomy in renal cell carcinoma. No convincing data exist regarding the minimum number of lymph nodes that should be removed at the time of nephrectomy to ensure an accurate staging. METHODS: Between 1987 and 2011, 850 patients with renal cell carcinoma underwent either partial or radical nephrectomy plus lymph node dissection (LND) at a single tertiary care institution (Tany N0-1Many ). Receiver operating characteristic curve coordinates were used to graph the probability of finding lymph node invasion according to the number of removed lymph nodes. Assuming that the likelihood of finding lymph node invasion according to the number of lymph nodes removed may be affected by patient characteristics, analyses were further stratified for clinical and pathological characteristics. RESULTS: The rate of lymph node metastases strongly correlated with the clinical and pathological characteristics of the patients. Fifteen lymph nodes need to be removed to achieve a 90% probability of detecting at least one metastatic lymph node. Only slight differences were recorded after stratification for clinical nodal status, the presence of metastases at diagnosis and pathological T stage. Finally, 13, 16 and 21 lymph nodes need to be removed to achieve a 90% probability of detecting lymph node invasion, if present, in the low risk (score 0-1), intermediate risk (score 2-3) and high risk (score 4-5) Mayo Clinic classification, respectively. CONCLUSION: The removal of 15 lymph nodes represents the lowest threshold for considering a staging LND as adequate. More extended LND should be pursued if unfavourable clinical and pathological characteristics are evident at diagnosis and/or during surgery.

Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?

PURPOSE: To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. MATERIALS AND METHODS: Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. RESULTS: The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). CONCLUSIONS: Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.

Towards the Definition of Radiomic Features and Clinical Indices to Enhance the Diagnosis of Clinically Significant Cancers in PI-RADS 4 and 5 Lesions.

Prostate cancer (PC) is the most frequently diagnosed cancer among adult men, and its incidence is increasing worldwide [...].

Prognostic value of extranodal extension and other lymph node parameters in patients with upper tract urothelial carcinoma.

PURPOSE: We assessed the prognostic value of extranodal extension and other lymph node parameters in a large multicenter cohort of patients with lymph node metastasis after radical nephroureterectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of 222 patients with lymph node metastasis treated with radical nephroureterectomy for upper tract urothelial carcinoma without neoadjuvant therapy. Each lymph node metastasis was microscopically evaluated for extranodal extension. RESULTS: A median of 4 lymph nodes (IQR 8) was removed. Two lymph nodes (IQR 2) were positive. Lymph node density was 51.3% (IQR 71.7%). Overall 110 patients (49.5%) had extranodal extension, which was associated with more advanced pT stage (p = 0.026). On multivariable analysis extranodal extension was associated with disease recurrence (p = 0.01) and cancer specific mortality (p = 0.013). When stratified by a 30% cutoff, lymph node density was associated with disease recurrence and cancer specific mortality on univariable but not multivariable analysis (p = 0.048 and 0.049, respectively). Adding extranodal extension to a multivariable model including pT stage and tumor architecture improved predictive accuracy for disease recurrence from 70.3% to 74.5% (p <0.001). Adding extranodal extension to a multivariable model including age, pT stage and tumor architecture improved predictive accuracy for cancer specific mortality from 70.6% to 74.4% (p <0.001). CONCLUSIONS: Extranodal extension is a powerful predictor of clinical outcomes in patients with upper tract urothelial carcinoma with lymph node metastasis. While other lymph node parameters seem to have limited clinical value, extranodal extension could help risk stratify patients with upper tract urothelial carcinoma and lymph node metastasis for better counseling and clinical trial design.

Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re-biopsy.

UNLABELLED: Study Type--Diagnostic (case series). Level of Evidence 4. What's known on the subject? And what does the study add? Multifocality, age, PSA values, and biopsy protocols regarding the predictive value of high grade PIN have been discussed extensively in the literature. Our study developed for the first time a predictive nomogram that could be helpful for patient counselling and to guide the urologist to perform rPBX after an initial diagnosis of isolated HGPIN. OBJECTIVE: • To evaluate factors that may predict prostate cancer (PCa) detection after the initial diagnosis of high-grade prostatic intra-epithelial neoplasia (HGPIN) on prostate biopsy (PBx) with six to 24 random cores. PATIENTS AND METHODS: • We retrospectively evaluated 262 patients submitted from 1998 to 2007 to prostate re-biopsy (rPBx) after an initial HGPIN diagnosis in tertiary academic centres. • HGPIN diagnosis was obtained on initial systematic PBx with six to 24 random cores. • All patients were re-biopsied with a 'saturation' rPBx with 20-26 cores, with a median time to rPBx of 12 months. • All slides were reviewed by expert uropathologists. RESULTS: • Plurifocal HGPIN (pHGPIN) was found in 115 patients and monofocal HGPIN (mHGPIN) was found in 147 patients. • In total, 108 and 154 patients, respectively, were submitted to >12-core initial PBx and ≤12-core initial PBx. • Overall PCa detection at rPBx was 31.7%. PSA level (7.7 vs 6.6 ng/mL; P= 0.031) and age (68 vs 64 years; P= 0.001) were significantly higher in patients with PCa at rPBx. • PCa detection was significantly higher in patients with a ≤12-core initial PBx than in those with a >12-core initial PBx (37.6% vs 23.1%; P= 0.01), as well as in patients with pHGPIN than in those with mHGPIN (40% vs 25.1%; P= 0.013). • At multivariable analysis, PSA level (P= 0.041; hazards ratio, HR, 1.08), age (P < 0.001; HR, 1.09), pHGPIN (P= 0.031; HR, 1.97) and ≤12-core initial PBx (P= 0.012; HR, 1.95) were independent predictors of PCa detection. • A nomogram including these four variables achieved 72% accuracy for predicting PCa detection after an initial HGPIN diagnosis. CONCLUSIONS: • PCa detection on saturation rPBx after an initial diagnosis of HGPIN is significantly higher in patients with a ≤12-core initial PBx than those with a >12-core initial PBx and in patients with pHGPIN than in those with mHGPIN. • We developed a simple prognostic tool for the prediction of PCa detection in patients with initial HGPIN diagnosis who were undergoing saturation rPBx.

Prognostic factors in a large multi-institutional series of papillary renal cell carcinoma.

OBJECTIVES: To investigate cancer-related outcomes and prognostic factors of papillary renal cell carcinoma (pRCC) in a large multicentre data set. Oncological outcome and prognostic factors of pRCC have been limitedly evaluated in comparison with the most common RCC subtype, clear cell RCC. PATIENTS AND METHODS: From a multicentre retrospective database, including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007, 577 patients with pRCC were identified. Univariable and multivariable Cox regression models were performed to identify prognostic factors predictive of recurrence-free survival (RFS) and cancer-specific survival (CSS) after surgery. RESULTS: At a median (interquartile range) follow-up of 39.2 (21.7-72) months, 81 (14%) patients had experienced disease progression and 63 (11%) patients had died from disease; the 5-year RFS estimate was 85.5%. In multivariable analysis, pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.9; P= 0.007) and Fuhrman nuclear grade (pooled P= 0.039) were all independent predictors of RFS; the 5-year CSS estimate was 87.9%. In Cox multivariable analysis, an independent predictive role was reconfirmed for mode of presentation (pooled P= 0.038), pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.4; P= 0.049) and Fuhrman nuclear grade (pooled P= 0.037). CONCLUSIONS: Patients with pRCC have a low risk of tumour recurrence and cancer-related death after surgery. Fuhrman nuclear grade was found to be a stronger predictor of both RFS and CSS, whereas only a non-statistically significant trend was found for the 2009 pathological T stage.

International validation of the prognostic value of subclassification for AJCC stage pT3 upper tract urothelial carcinoma of the renal pelvis.

UNLABELLED: What's known on the subject? and What does the study add? Tumour stage is a powerful predictor of clinical outcomes and the most important factor driving clinical decision-making after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). It has been suggested that renal pelvic pT3 subclassification into microscopic infiltration of the renal parenchyma (pT3a) versus macroscopic infiltration or invasion of peripelvic adipose tissue (pT3b) has strong prognostic value. This is an external validation study of the prognostic value of pT3 subclassification of renal pelvic UTUC in a large international cohort of patients treated with RNU. pT3b UTUC is associated with features of aggressive tumour biology, disease recurrence and cancer-specific mortality. However, pT3 subclassification is not an independent predictor of clinical outcomes. OBJECTIVE: To externally validate the prognostic value of subclassification of pT3 renal pelvic upper tract urothelial carcinoma (UTUC) in a large international cohort of patients treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: The RNU specimens with pT3 UTUC of the renal pelvis from 284 patients at 11 centres located in Asia, North America and Europe were retrospectively evaluated. All specimens were reviewed by genitourinary pathologists at each institution. Tumours were categorized as pT3a (microscopic infiltration of the renal parenchyma) or pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue). RESULTS: Overall, 148 (52%) tumours were classified as pT3a and 136 (48%) as pT3b. Patients with pT3b disease were more likely to have high-grade tumours and sessile tumour architecture (all P ≤ 0.02). Patients with pT3b tumours were at increased risk of disease recurrence (5-year estimates: 55% versus 42%, P = 0.012) and cancer-specific mortality (CSM) (5-year estimates: 48% versus 40%, P = 0.04). Lymph node status, tumour architecture and tumour grade were independently associated with disease recurrence, whereas lymph node status, tumour architecture and lymphovascular invasion were independently associated with CSM. Subclassification of pT3 tumours was not associated with recurrence or CSM in multivariable analyses. CONCLUSION: Patients with pT3b UTUC were more likely to have tumours with aggressive pathological features and were at higher risk of disease recurrence and CSM after RNU compared with patients with pT3a disease. However, the pT3 subclassification did not remain an independent predictor of disease recurrence or CSM after controlling for tumour grade, lymph node status, tumour architecture and lymphovascular invasion.

Prostate saturation biopsy following a first negative biopsy: state of the art.

INTRODUCTION: Saturation prostate biopsy (SPBx) has been initially introduced to improve prostate cancer (PCa) detection rate (DR) in the repeat setting. Nevertheless, the optimal number and the most appropriate location of the cores, together with the timing to perform a second PBx and the eventual modification of the PBx protocols according to the different clinical situations, are matters of debate. The aim of this review is to perform a critical analysis of the literature about the actual role of SPBx in the repeat setting. MATERIALS AND METHODS: We performed a systematic review of the literature since 1995 up to 2011. Electronic searches were limited to the English language, using the MEDLINE database. The key words 'saturation prostate biopsy' and 'repeated prostate biopsy' were used. RESULTS: SPBx improves PCa DR if clinical suspicion persists after previous biopsy with negative findings and provides an accurate prediction of prostate tumor volume and grade, even if the issue about the number and locations of the cores is still a matter of debate. CONCLUSIONS: At present, SPBx seems to be really necessary in men with persistent suspicion of PCa after negative initial biopsy and probably in patients with a multifocal high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. In the remaining situations, adopting an individualized scheme is preferable.