The Impact of Second Opinion Expert Pathology Review in Patient Management at the Time of Transurethral Resection of the Bladder.

BACKGROUND AND OBJECTIVE: Pathological features in non-muscle-invasive bladder cancer specimens are pivotal in determining correct patients' therapeutic management. Sparse data exist regarding the importance of second opinion performed by an expert uropathologist. This study aimed to assess the importance of a second opinion by an expert uropathologist in the management of bladder cancer. METHODS: The study relied on 272 bladder cancer specimens from 231 patients seeking a pathology second opinion after transurethral resection of the bladder for a clinical suspicion of bladder cancer, relapse, or second-look procedure. Pathology second opinion was offered by an experienced fellowship-trained uropathologist. Discrepancies were recorded considering primary tumor staging, the presence of muscularis propria, and the presence of histological variants. Cases were categorized as no significant discordance, major discordance without management change, and major discordance with management change according to the European Urology Association (EAU) guidelines. KEY FINDINGS AND LIMITATIONS: Among 272 second opinion cases, 39% (108/272) had major discordance and 28% (75/272) had major discordance with change in management according to the EAU guidelines. Upstaging and downstaging were reported in 66 (24%) patients. Improper identification of the presence of muscularis propria was found in 46 (17%) cases, of which 11 (4%) were deemed clinically relevant. Differences regarding the presence of histological variants were diagnosed in 40 cases (15%), resulting in eight (3%) changes in clinical management. In ten specimens (4%), multiple clinically relevant discrepancies were found. CONCLUSIONS AND CLINICAL IMPLICATIONS: The second opinion evaluation changed the clinical management in 25% of the cases. These results support the importance of specimen review by an expert uropathologist as a major driver in the correct bladder cancer management. PATIENT SUMMARY: We investigated the importance of a second opinion performed by an expert uropathologist in the management of bladder cancer. We found that 25% had their treatment plan changed due to the revised pathological report.

Peri- and post-operative outcomes of robot-assisted radical cystectomy after the implementation of the EAU guidelines recommendations for collecting and reporting complications at a high-volume referral center.

PURPOSE: No studies relied on a standardized methodology to collect postoperative complications after robot-assisted radical cystectomy (RARC). The aim of our study was to evaluate peri- and post-operative outcomes of patients undergoing RARC adhering to the European Association of Urology (EAU) recommendations for reporting surgical outcomes and using a long postoperative follow-up. MATERIALS AND METHODS: 246 patients who underwent RARC with intracorporal urinary diversion at a single tertiary referral center with a postoperative follow-up ≥ 1 year for survivors. Postoperative outcomes were collected prospectively by interviews done by medical doctors. Complications were scored using the Clavien-Dindo classification (CD), grouped by type and severity (severe: CD score ≥ 3). We described peri- and post-operative outcomes and complication chronological distribution. RESULTS: Overall, 16 (6.5%) and 225 patients (91%) experienced intraoperative and postoperative complications, respectively. Moreover, 139 (57%) experienced severe complications. The most common any-grade and severe complications were infectious (72%) and genitourinary (35%), respectively. Overall, 52% of complications (358/682) occurred within 10 days from surgery, and 51% of severe complications (106/207) occurred within 35 days. However, 13% of complications (90/682) and 28% of severe complications (59/207) occurred 3 months after surgery. The earliest complications were fever of unknown origins and paralytic ileus (median time-to-complication [mTTC]: 4 days), the latest complications were urinary tract infection (mTTC: 40 days) and hydronephrosis/ureteral obstruction (mTTC: 70 days). CONCLUSIONS: The rate of postoperative complications after RARC is > 90% when a standardized collection method and a long follow-up is implemented. These results should be used to identify potential areas of improvement and for preoperative patient counseling.

Use of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT for lymph node assessment before radical cystectomy in bladder cancer patients.

OBJECTIVE: To assess the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomograpy (PET)/computed tomography (CT) in nodal staging before radical cystectomy (RC) and pelvic lymph node dissection (PLND) for bladder cancer (BCa). MATERIALS AND METHODS: This analysis was based on a cohort of 199 BCa patients undergoing RC and bilateral PLND between 2015 and 2022. Neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) was administered after oncological evaluation. All patients received preoperative 18F-FDG PET/CT to assess extravesical disease. Point estimates for true negative, false negative, false positive, true positive, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of conventional imaging and PET/CT were calculated. Subgroup analysis in patients receiving neoadjuvant treatment was performed. RESULTS: At preoperative evaluation, 30 patients (15.1%) had 48 suspicious nodal spots on 18F-FDG PET/CT. At RC and bilateral PLND, a total of 4871 lymph nodes (LNs) were removed with 237 node metastases corresponding to 126 different regions. Pathological node metastases were found in 17/30 (57%) vs 39/169 patients (23%) with suspicious vs negative preoperative 18F-FDG PET/CT, respectively (sensitivity = 0.30, specificity = 0.91, PPV = 0.57, NPV = 0.77, accuracy = 0.74). On per-region analysis including 1367 nodal regions, LN involvement was found in 19/48 (39%) vs 105/1319 (8%) suspicious vs negative regions at PET/CT, respectively (sensitivity = 0.15, specificity = 0.98, PPV = 0.40, NPV = 0.92, ACC = 0.90). Similar results were observed for patients receiving NAC (n = 44, 32.1%) and NAI (n = 93, 67.9% [per-patient: sensitivity = 0.36, specificity = 0.91, PPV = 0.59, NPV = 0.80, accuracy = 0.77; per-region: sensitivity = 0.12, specificity = 0.98, PPV = 0.32, NPV = 0.93, ACC = 0.91]). Study limitations include its retrospective design and limited patient numbers. CONCLUSIONS: In eight out of 10 patients with negative preoperative 18F-FDG PET/CT, pN0 disease was confirmed at final pathology. No differences were found based on NAC vs NAI treatment. These findings suggest that 18F-FDG PET/CT could play a role in the preoperative evaluation of nodal metastases in BCa patients, although its cost-effectiveness is uncertain.

Prediction of the Need for an Extended Lymphadenectomy at the Time of Radical Cystectomy in Patients with Bladder Cancer.

BACKGROUND: A prospective randomized trial (LEA AUO AB 25/02) found no survival benefit in extended compared with limited pelvic lymph node dissection (PLND) templates in bladder cancer (BCa) patients treated with radical cystectomy (RC). However, the rate of lymph node invasion (LNI) in the standard and extended templates was lower than estimated. OBJECTIVE: To assess the accuracy of preoperative clinical and pathological parameters to predict LNI and to develop a model to preoperatively select candidates for the extended PLND templates. DESIGN, SETTING, AND PARTICIPANTS: A total of 903 BCa patients treated at a single institution were retrospectively identified. The primary outcome was to identify preoperatively the risk of LNI to tailor the type of PLND. The extended PLND templates consisted in the removal of pelvic lymph nodes together with the common iliac, presacral, para-aortocaval, interaortocaval, and paracaval sites up to the inferior mesenteric artery. INTERVENTION: A total of 903 BCa patients were treated with RC and bilateral extended PLND templates. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Several models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses. A nomogram predicting LNI in the extended pattern was developed and validated internally. RESULTS AND LIMITATIONS: Overall, 55 patients (6.1%) had LNI in the extended PLND templates at RC. The median number of nodes removed was 19 (interquartile range: 13-26). A model including age, clinical T stage, clinical node stage, lymphovascular invasion, and presence of carcinoma in situ at the last transurethral resection before RC was developed. The AUC of this model is 73%. Using a cutoff of 3%, 108 extended PLNDs (12%) would be spared and only two LNIs (3%) would be missed. The main limitations of our model are the retrospective nature of the data, lack of external validation, and low rate of LNI. CONCLUSIONS: This is the first proposed model to predict LNI in the extended PLND templates. This model might help urologists identify which patients might benefit from an extended PLND at the time of RC, reserving a standard PLND for all the others. PATIENT SUMMARY: We developed the first nomogram to predict lymph node invasion (LNI) in the extended pelvic lymph node dissection templates in bladder cancer patients treated with radical cystectomy. The adoption of our model to identify candidates for the extended pelvic lymph node dissection templates could avoid up to 12% of these procedures at the cost of missing only 3% of patients with LNI.

Evaluation of Cause of Death After Radical Cystectomy for Patients With Bladder Cancer: The Impact of Age at the Time of Surgery.

INTRODUCTION: Patients with bladder cancer treated with radical cystectomy (RC) have heterogeneous results in term of cancer-specific (CSM) and other cause mortality (OCM). Our aim is to assess the impact of age on cause of death after RC. PATIENTS AND METHODS: We retrospectively analyzed the data of 1222 patients treated with RC and bilateral pelvic lymph node dissection owing to nonmetastatic bladder cancer between 1990 and 2013. Patients were stratified according to age (< 59 vs. 60-69 vs. 70-79 vs. ≥ 80 years), tumor T stage at RC (pT0-T2 vs. pT3-T4), and tumor N stage at RC (pN+ vs. pN0). Competing-risks survival analyses were used to estimate CSM and OCM rates. RESULTS: With a median follow up of 6 years, 92 (7.5%) and 385 (31.5%) OCM and CSM were recorded. The 5-year CSM and OCM rates were 40% and 8.8%, respectively. After stratification according to disease stage and patient age, CSM emerged as the main cause of mortality in all patient subgroups. The 5-year OCM was 4.6%, 4.8%, 11%, and 32% for patients aged < 60 years versus 60 to 69 years versus 70 to 79 years versus ≥ 80 years, respectively. The 5-years CSM was 34%, 45%, 35%, and 56% for patients aged < 60 years versus 60 to 69 years versus 70 to 79 years versus ≥ 80 years, respectively. Similar findings were observed stratifying the population according to pathologic T and N stage. CONCLUSION: CSM is the preponderant cause of death for all the patients, regardless of age or stage. In this regard, RC also seems to be a reasonable approach for octogenarians.

Feasibility and Clinical Roles of Different Substaging Systems at First and Second Transurethral Resection in Patients with T1 High-Grade Bladder Cancer.

BACKGROUND: Decision making in T1 high-grade bladder cancer patients remains a challenging issue in urologic practice. OBJECTIVE: To assess the feasibility and potential prognostic role of three different substaging systems in specimens from both primary and second transurethral resection (TUR) of the bladder in T1 high-grade bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 250 consecutive, confirmed pure transitional T1 high-grade bladder tumors submitted to second TUR entered the retrospective study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Feasibility of two already clinically tested microstaging systems (anatomy-based T1a/T1b/T1c and micrometric T1m/T1e with 0.5-mm thresholds of invasion) and that of a micrometric substage designed by the authors and based on a 1-mm threshold of invasion (Rete Oncologica Lombarda [ROL] system) was assessed by five independent uropathologists on both first and second TUR specimens. Univariable Cox proportional hazards models were attempted to identify significant independent predictors of recurrence and progression after TUR. Kaplan-Meier curves were plotted to compare different substaging methods analyzing recurrence and progression. RESULTS AND LIMITATIONS: The ROL system proved to be feasible in nearly all cases at both first and second TUR. Median follow-up was 60 mo. The univariate Cox regression analysis documented the ROL substage (ROL2 vs ROL1) to be the only statistically significant predictor of progression (hazard ratio: 2.01; 95% CI, 1.03-3.79; p<0.03). For the first time to our knowledge, the substage was investigated and used to assess T1 tumors found at second TUR, registering a high rate of feasibility. CONCLUSIONS: T1 microstaging using different procedures is feasible on both primary- and second-TUR specimens. A high rate of feasibility may be expected for T1m/T1e and ROL systems. The clinical role of microstaging on second TUR remains to be defined. PATIENT SUMMARY: The Rete Oncologica Lombarda system showed feasible results in T1 high-grade bladder tumors. Our substratification was predictive of progression of disease.

Incidence and Predictors of 30-Day Readmission in Patients Treated With Radical Cystectomy: A Single Center European Experience.

INTRODUCTION: Previous studies showed high hospital readmission rates after radical cystectomy (RC) for bladder cancer (BCa), however at the time results of a European series analyzing this event were still missing. PATIENTS AND METHODS: Overall, 1090 consecutive BCa patients treated with RC at a single center between January 2002 and August 2012 were identified. Logistic regression analyses were used to test the association between covariates and 30-day readmission in the overall population and after stratifying according age at the time of surgery. RESULTS: Mean length of stay (LOS) was 19 days (median, 16 days), and the overall 30-day readmission rate was 12.2%. The most frequent reasons for readmission at 30 days were ileus (n = 15; 11.3%), lymphoceles (n = 11; 8.3%), wound infection (n = 10; 7.5%), and fever (n = 12; 9.0%). In multivariable logistic regression analysis, age (odds ratio [OR], 1.02; P = .04) and LOS (OR, 0.94; P < .01) were associated with 30-day readmission. However, when analyzed according age at the time of surgery, a beneficial effect from a longer LOS was observed only in patients older than 70 years (P < .003). CONCLUSION: In the first European series on the effect of 30-day readmission, our data showed that even with a relative high mean LOS, 30-day readmission remained an ineradicable factor. Of note, older patients and shorter LOS were associated with an increased risk of readmission at 30 days, however, an increase of LOS to prevent readmission seemed effective only in patients older than 70 years.