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.

Features, risk factors and clinical outcome of "very late" recurrences after surgery for localized renal carcinoma: A retrospective evaluation of a cohort with a minimum of 10 years of follow up.

OBJECTIVE: To evaluate the features and the predictors of "very late" recurrences after surgery for localized renal cell carcinoma. METHODS: Since 1983, an institutional database with data of more than 2300 consecutive patients treated for renal cancer has been prospectively maintained. Patients N0 /Nx M0 followed for a minimum of 10 years without recurrences were retrieved. The site, time and treatment of recurrences observed afterwards were recorded, and the predictors were investigated by Cox regression analysis. RESULTS: A total of 554 patients (231 women, 323 men; age 59.3 ± 11.6 years) followed for a mean/median time of 15.1/13.6 years (range 10.0-34.1 years) were analyzed. A recurrence was observed in 26 patients (4.6%) after a mean/median interval of 13.3/12.3 years (range 10.5-30.2 years). The pathological stage 2/3 was the only independent predictor of recurrence (P = 0.003), and it was related also to the latency of recurrence (mean/median latency 15.4/14.0, 11.4/10.8 and 12.5/12.0 years, respectively, for stage 1, 2 and 3; P < 0.005 for stage 1 vs stage 2 or 3). The contralateral kidney was the most frequent site of relapse in patients with stage pT1, whereas multiple sites were more frequent for stage pT2 and pT3. CONCLUSIONS: The risk of a "very late" recurrence of renal cancer is approximately 5%, and it depends on the pathological stage. For stage pT1, the kidney/s should be surveilled for indefinite time, preferably by ultrasound to reduce the X-ray exposition; for stage pT2 and pT3, the abdomen and the lungs should be monitored, by computed tomography scan during the first years, and then by abdominal ultrasound and chest X-ray.

Venous tumor thrombus consistency is not predictive of survival in patients with renal cell carcinoma: A retrospective study of 147 patients.

OBJECTIVES: To evaluate the prognostic role of venous tumor thrombus consistency in patients with renal cell carcinoma. METHODS: A retrospective evaluation of the data of patients with renal cell carcinoma and a tumor thrombosis submitted to surgery from 2000 to 2013 was carried out. Histological slides were revised by two uropathologists, blinded of the clinical outcome, to assess venous tumor thrombus consistency classified as solid venous tumor thrombus consistency or friable venous tumor thrombus consistency. The statistical correlation between venous tumor thrombus consistency and other adverse features was assessed. Then the predictive ability of an integrated prognostic model, generated by Cox regression and random survival forest, was evaluated, with and without the inclusion of venous tumor thrombus consistency, by integrated Brier score, dynamic receiver operating characteristic curves, integrated discrimination improvement index and category-less net reclassification index. RESULTS: The data of 147 patients were analyzed, 79 with a solid venous tumor thrombus consistency and 68 with a friable venous tumor thrombus consistency, followed for a median period of 40.5 months. Venous tumor thrombus consistency was assessed with a high interobserver agreement (145/147 cases). The presence of a friable venous tumor thrombus consistency was associated with some adverse prognostic factors (symptoms, lymphnodal and distant metastasis, larger tumor diameter, higher cephalad thrombosis level, necrosis, microvascular invasion) and to a worse cancer-specific and overall survival at univariate analysis. However, venous tumor thrombus consistency was not predictive of survival, and did not improve the performance of a multivariable model that included a set of informative predictors. CONCLUSION: Venous tumor thrombus consistency does not seem to have an independent prognostic role in patients with renal cell carcinoma.

TriMatch comparison of the efficacy of FloSeal versus TachoSil versus no hemostatic agents for partial nephrectomy: results from a large multicenter dataset.

OBJECTIVES: To evaluate the efficacy of hemostatic agents, TachoSil and FloSeal, during partial nephrectomy using a large multicenter dataset. METHODS: Data of 1055 patients who underwent partial nephrectomy between January 2009 and December 2012 in 19 Italian centers were collected within an observational multicentric study (RECORd Project). The decision whether or not to use hemostatic agents after renorrhaphy and the type of hemostatic agents applied was adopted according to the centers' and surgeons' preference. A TriMatch propensity score analysis was applied to balance three study groups (no hemostatic agents, TachoSil, FloSeal) for sex, age, surgical indication (elective/relative vs imperative), clinical stage (cT1a vs cT1b), tumor exophyticity, approach (open vs minimally invasive), technique (standard partial nephrectomy vs simple enucleation), preoperative hemoglobin and creatinine. Postoperative complications and variation of hemoglobin and creatinine values between preoperative versus third postoperative day were compared. RESULTS: TriMatch analysis allowed us to obtain 66 well-balanced triplets. No differences were found in terms of outcomes between the study groups. CONCLUSIONS: The present findings suggest that adding hemostatic agents to renorraphy during partial nephrectomy does not provide better surgical outcomes.

The Accuracy of Transurethral Bladder Resection in Detecting Bladder Cancer Histological Variants and Their Prognostic Value at Radical Cystectomy.

OBJECTIVES: to investigate the accuracy of transurethral resection of bladder tumours (TURBT) in detecting histological variants (BHV) at radical cystectomy (RC) and to evaluate the impact of TURBT before cystectomy on oncological outcomes. METHODS: Data of 410 consecutive RCs were assessed. Positive and negative predictive values were used to assess the accuracy of TURBT in detecting BHV. Cohen's Kappa coefficient was used to calculate the agreement grade. Logistic regression analysis predicted features based on the presence of BHV at TURBT. Multivariable backward conditional Cox regression analysis was used to estimate oncological outcomes. RESULTS: A total of 73 patients (17.8%) showed BHV at TURBT as compared to 108 (26.3%) at RC. A moderate agreement in histological diagnosis was found between TURBT and RC (0.58). However, sensitivity and specificity in detecting BHV were 56% and 96%, respectively. Furthermore, positive predictive value (PPV) was 84.7% and negative predictive value (NPV) was 84.6%. Presence of BHV at TURBT was an independent predictor for pathologic upstage, albeit not a predictor for positive nodes or positive surgical margins. However, at multivariable analysis adjusted for all confounders, presence of BHV at TURBT was an independent predictor for recurrence after RC, but not for survival. Conversely, the presence of BHV at RC was an independent predictor for both recurrence and survival. CONCLUSION: There was a moderate agreement between TURBT and RC histopathological findings. TURBT, alone, could not provide an accurate and definitive histological diagnosis. Detection of BHV in TURBT specimens is not an independent predictor of oncological outcomes; indeed, only pathological features at RC are associated with worse survival. However, BHV presence in cystectomy specimens resulted as an independent predictor of both cancer-specific and overall mortality.

Oncological outcomes of concomitant carcinoma in situ at radical cystectomy in pure urothelial bladder cancer and in histological variants.

INTRODUCTION: The presence of carcinoma in situ at transurethral resection is known to increase the risk of recurrence and progression to invasive disease. However, the evidence regarding the prognostic role of concomitant carcinoma in situ after radical cystectomy due to bladder cancer is controversial. Moreover, concomitant carcinoma in situ was found to be significantly associated with bladder histological variants. The aim of our study is to evaluate whether the presence of concomitant carcinoma in situ at radical cystectomy, impacts on recurrence and survival outcomes in pure urothelial bladder cancer, compared to histological variants. METHODS: We evaluated 410 consecutive patients diagnosed with non-metastatic bladder cancer and treated with radical cystectomy at a single tertiary referral centre between January 2009 and May 2019. Patients were stratified according to the presence of carcinoma in situ. The Kaplan-Meier method was used to compare recurrence free, cancer specific and overall survival in pure urothelial and histological variants. Cox proportional hazards regression analyses model was used to predict recurrence, cancer specific and overall mortality in pure urothelial and histological variants bladder cancer, according to pathological stage. RESULTS: Median age was 71 years. 340 patients (82%) were male. At a median follow-up of 32 months, disease recurrence, cancer specific mortality and overall mortality were, 37% (155 patients), 32.9% (135 patients) and 46.6% (191 patients), respectively. Concomitant and pure carcinoma in situ were found in 39% and 19% of radical cystectomy specimens, respectively. Concomitant carcinoma in situ was more frequent in patients with histological variants (50.9%) compared to pure urothelial bladder cancer (35.4%) (P-value <.001) and was associated with worst pathological features (lymphovascular invasion, lymph node involvement and non-organ confined disease). Recurrence free survival at Kaplan-Meyer analyses was significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001), similarly for patients without carcinoma in situ compared with those with concomitant Cis (P =.02) at radical cystectomy. Cancer specific and overall survival were significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001). Conversely no significant difference was found between patients without carcinoma in situ and with concomitant carcinoma in situ (P>0.1) at radical cystectomy Moreover, concomitant carcinoma in situ at radical cystectomy in histological variants is associated with higher free recurrence rate compared to the other groups. At multivariate Cox proportional hazards regression analyses the presence of carcinoma in situ at radical cystectomy was not associated with any survival effect or recurrence (all P > .05) in the overall population and when patients are stratified according to histology. However, concomitant carcinoma in situ represents an independent predictor of recurrence in the subgroup of patients with organ confined disease in case of urothelial bladder cancer and histological variants. CONCLUSION: Concomitant carcinoma in situ should be considered a proxy of aggressiveness in bladder cancer after radical cystectomy. Based on its prognostic implications, concomitant carcinoma in situ should be considered for strict follow-up in patients with organ confined disease which may deserve adjuvant treatment both in pure urothelial bladder cancer and histological variants.

Recurrent retroperitoneal solitary fibrous tumor: a case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm described initially in visceral pleura but can occasionally involve other sites such as the urinary tract. Extrapleural localizations are often indolent but some malignant SFTs have been described. The treatment and the most important prognostic factor for SFT seem to be complete resection of the neoplasm. CASE REPORT: We report the 10-year history of a retroperitoneal SFT, which recurred twice after conservative management, and was eventually treated with en bloc resection of the mass, the bladder, and the prostate, and urinary diversion by ileal conduit. To our knowledge, this case has the longest follow-up in the literature. CONCLUSION: Extrapleural SFTs often have indolent but unpredictable behavior as they can recur even after many years. Some histologic features are associated with the malignancy of these tumors. Complete resection of the neoplasm is the most important prognostic factor. Patients with SFT should be considered for a very long follow-up after the surgery due to the risk of possible late recurrences.

External Validation of the Arterial-Based Complexity Score and First Head-to-Head Comparison With the R.E.N.A.L. and PADUA Scores and C-index.

INTRODUCTION: We performed an external validation of the arterial-based complexity (ABC) score using a head-to-head comparison with the R.E.N.A.L. (radius, exophytic/endophytic tumor properties, nearness of tumor to deepest portion of collecting system or sinus, anterior/posterior descriptor, location relative to the polar line), PADUA (preoperative aspects and dimension for anatomic classification of renal tumors), and C-index scores for the prediction of surgical outcomes after partial nephrectomy. MATERIALS AND METHODS: The data from a series of consecutive open or robot-assisted partial nephrectomies performed from January 2014 to July 2016 by 4 expert surgeons at a tertiary academic institution were reviewed. After dedicated training, 1 urologist not involved in the surgical procedures evaluated the cross-sectional imaging studies and assigned the nephrometry score using the 4 nephrometry scoring systems. The predictive performance of the ABC and other scoring systems was tested in univariate and multivariable fashion. RESULTS: Overall, 234 patients were recruited (148 men and 86 women; age, 63 ± 10.9 years). The scores were all related to the estimated blood loss, use of hilar clamping, ischemia time, operative time, length of stay, and MIC (margin status, ischemia time, complications) score. They were not related to the occurrence of postoperative complications or, for the C-index and ABC score, the length of stay. In a head-to-head comparison, the ABC was not inferior only to the C-index relative to the occurrence of complications and MIC score, with borderline statistical significance. On multivariate analysis, the ABC score provided significant improvement only for the prediction of the operative and ischemia times. However, its performance was inferior to that of the other scoring systems. In addition, only the PADUA score improved the prediction of artery clamping and MIC score, and only the R.E.N.A.L. score showed an advantage for the prediction of the estimated blood loss. CONCLUSION: The predictive ability of ABC was inferior to that of well-established existing nephrometry scoring systems, such as the PADUA and R.E.N.A.L. scores.

External histopathological validation of the surface-intermediate-base margin score.

PURPOSE: The surface, intermediate, and basis (SIB) is a system based on surgeon׳s visual assessment of the thickness of healthy parenchyma remaining on the intrarenal portion of the tumor. This system has been proposed to standardize the nomenclature of the resection technique (RT) during partial nephrectomy (PN). Our study aims at evaluating whether the SIB score visually assigned is related to the thickness of parenchyma measured by microscopy. MATERIALS AND METHODS: Data of 52 patients submitted to PN from April to October 2015 were perspectively collected. All the excisions were performed following a "nonanatomical" strategy according to our institutional intention to resect the tumor with a visible margin of parenchyma. After the removal of the specimen, 2 trained examiners applied the SIB system: the intrarenal portion of the nodule was ideally divided into 3 circumferential sectors (surface, intermediate, and basis); on each of these was identified the area covered by the lowest amount of parenchyma (score specific area [SSA]); and a score descriptive of the thickness of parenchyma was assigned to each area. The RT performed (enucleation, enucleoresection, or wedge resection) was defined by the sum of the scores. The same examiners inked every SSAs with a different color and then dedicated pathologists, blinded of the scores assigned, and microscopically measured the parenchyma covering each SSA. The relationship between these values and the SIB scores was assessed. RESULTS: According to the SIB nomenclature, the technique performed was enucleation for 31 patients (60%), enucleoresection for 16 (31%), and wedge resection for 5 (9%). For the surface SSA, the median/mean values of the thickness for S = 0 vs. S = 1 was 0.35/0.84 vs. 2.00/2.26mm and for the intermediate or base SSA, the median/mean value of the thickness for S = 0 vs. 1 vs. 2 was 0.35/0.47 vs. 1.00/1.50 vs. 2.00.5/2.33mm. All the comparison reached statistical significance. CONCLUSIONS: The visual description of the surgical plane followed during PN according to the SIB system is related to the microscopic thickness of healthy parenchyma covering the tumor. The SIB system can correctly discriminate among different R techniques, and therefore could be a crucial tool to standardize the nomenclature of PN.

Features of Ipsilateral Renal Recurrences After Partial Nephrectomy: A Proposal of a Pathogenetic Classification.

BACKGROUND: Poor data are reported on the pathogenesis of ipsilateral relapse (IR) after partial nephrectomy (PN). The objective of this study was to investigate features of IR after PN with the intention to propose a pathogenetic classification. MATERIALS AND METHODS: Retrospective consultation of an institutional database that stores the data of 683 patients submitted to PN since 1993. The clinical, radiological, and follow-up data of the cases submitted to salvage nephrectomy due to an IR were analyzed. The slides of the sections from the tumor-parenchyma interface of PN and the bed of resection from the specimen of nephrectomy were reviewed. RESULTS: Eighteen patients were submitted to salvage nephrectomy for an IR. In 12 cases the IR harbored into the site of PN and a mixture of cancer cells and granulomatous reaction was found at the resection bed (IR type A). In the remaining 6, in microscopy of the resection bed was found only fibrosis: 3 of these cases had a clear-cell renal cell carcinoma (RCC) with diffuse microvascular embolization and the relapse in the same portion of the kidney of the primary tumor (IR type B); the other 3 had a non-clear-cell RCC and the primary and relapsing tumors were located in distinct portions of the kidney (IR type C). Six patients (4 IR type A, 2 type B) had a further progression and 5 of them died due to RCC. CONCLUSION: More frequently an IR is due to the incomplete resection of the primary tumor (IR type A), in a minority of the cases to the local spread of the tumor by microvascular embolization (IR type B), or true multifocality (IR type C). The prognosis of IR not due to multifocality (type A and B) is poor, despite salvage nephrectomy.

Positive surgical margins and early oncological outcomes of robotic vs open radical prostatectomy at a medium case-load institution.

BACKGROUND: The aim of this study was to analyze the rates of positive surgical margins (PSM) after radical prostatectomy in patients undergoing robotic surgery (robot assisted laparoscopic prostatectomy [RALP]) compared with those undergoing open surgery (radical retropubic prostatectomy [RRP]), at an institution with medium case load. METHODS: Retrospective consultation of a perspectively-maintained database that stores the data of all the patients submitted to radical prostatectomy at our institution since 1/2008. The indication to RRP vs. RALP was based almost exclusively on the period of the study: RRP was the sole available option between 1/2008 and 3/2010 and afterwards RALP become the standard of treatment, once a learning curve of 50 cases was concluded. A PSM was defined as the presence of cancer at the inked surface of prostate. A univariate and multivariate binary logistic regression estimated which factors were related to PSMs. RESULTS: The data of 576 patients (285 RRP, 291 RALP) were evaluated. The overall PSM rate was 28.1% (162/414 patients; 20.6% for pT2 stage, 51.8% for pT>2); overall PSM rate for RRP vs. RALP was 31.9% vs. 24.4 % (P=0.044). At multivariable analysis the factors related to the risk of PSM were stage pT>2 (RR 2.979, P=0.001), Gleason Score >6 (RR 1.662, P=0.026), the volume of tumor (RR 1.019, P=0.008) and the surgical technique (RALP vs. RRP, RR 0.647, P=0.039). CONCLUSIONS: In a series from a medium case-load institution, once data are adjusted for local staging, tumor volume and Gleason score, the risk of PSM is lower for RALP than RRP. This evidence could be of support for health-care practitioners to introduce robotic systems.

Analysis of Circulating Tumor Cells in Prostate Cancer Patients at PSA Recurrence and Review of the Literature.

BACKGROUND: Circulating tumor cells have been described in prostate cancer patients at diagnosis and in the metastatic phase but little is known on their role at biochemical PSA recurrence. PATIENTS AND METHODS: Patients radically cured with either prostatectomy or radiotherapy were sequentially included at PSA recurrence. The presence of CTCs was evaluated by the CellSearch system. RESULTS: Twenty-nine patients were accrued at PSA recurrence. Median PSA at recurrence was 7.2 ng/ml (range=3.86-51.0 ng/ml). The median time to PSA progression was 4.66 years (range=0.1-16 years). CTCs were detected in one patient (3%) with low numbers (1 CTC/7.5 ml). CONCLUSION: In patients radically cured for prostate cancer at biochemical recurrence, CTCs are detected at very low levels in a minority of patients. Further studies are required to investigate alternative methods of CTC detection and the possible role of the bone marrow pre-metastatic niche at biochemical recurrence.

A prospective, multicenter evaluation of predictive factors for positive surgical margins after nephron-sparing surgery for renal cell carcinoma: the RECORd1 Italian Project.

BACKGROUND: The purpose of this study was to evaluate the predictors of positive margins in one of the largest available prospective multi-institutional studies. PATIENTS AND METHODS: We evaluated all patients who underwent NSS for radiologically diagnosed kidney tumors between January 2009 and December 2012 at 19 urological Italian centers (Registry of Conservative Renal Surgery [RECORd] project). Preoperative and anthropometric data, comorbidities, intraoperative and postoperative outcomes, and histological findings were analyzed. The negative and PSMs were compared according to the clinical and surgical variables. Multivariable logistic regression models were applied to analyze predictors of PSMs. RESULTS: Eight hundred consecutive patients were evaluated. Seven hundred sixty-one (95.1%) and 39 patients (4.9%) achieved negative and PSMs, respectively. Patients with PSMs were significantly older compared with those with negative margins (median age: 66.6 vs. 61.8 years, respectively; P = .001). A higher incidence of PSMs was observed when NSS was performed for renal masses located in the upper pole (P = .001). A lower rate of PSMs was found in patients treated with simple enucleation rather than standard PN (1.6% vs. 7.4%, respectively; P < .0001). A greater incidence of PSMs was found in Fuhrman 3/4 tumors (11.3%; P < .0001). At multivariable analysis, age (odds ratio [OR], 1.04; P = .01), upper pole tumor location (OR, 2.85; P = .005), standard PN (OR, 3.45; P = .004), and Fuhrman 3-4 nuclear grade (OR, 4.81; P = .001) were found to be independent predictors of PSMs. CONCLUSION: In our multi-institutional report, young age, simple enucleation, middle or lower tumor location, and low-grade tumor were demonstrated to be independent predictors of negative SMs.