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Objective: Comparative effectiveness studies comparing trimodal therapy (TMT) to radical cystectomy (RC) are typically hindered by selection bias where TMT is usually reserved to patients with poor overall health status. We developed a novel approach by matching patients based on their calculated other-cause mortality (OCM) risk. Using this homogeneous cohort, we tested the impact of TMT vs RC on cancer-specific mortality (CSM)., Materials and Methods: The Surveillance, Epidemiology and End Results (SEER) 2004-2018 database was queried to identify patients diagnosed with cT2-4N0M0 muscle-invasive bladder cancer (MIBC). A Fine-Gray competing-risk regression model calculating the 5-year OCM risk was used to create a 1:1 propensity-score matched-cohort of patients treated with RC or TMT. Cumulative incidence and competing-risk regression analyses tested the impact of treatment type (RC vs TMT) on CSM. Patients were further stratified according to clinical T stage (cT2 vs cT3-4) in sensitivity analyses., Results: We identified 6,587 patients (76%) treated with RC and 2,057 (24%) with TMT. The median follow-up was 3.0 years. In the unmatched-cohort, 5-year OCM and CSM rates were 14% and 40% for RC vs 23% and 47% in TMT group, respectively (all P < 0.001). Our matched-cohort included 4,074 patients, equally distributed for treatment type, with no difference in 5-year OCM (HR: 0.98, 95% CI: 0.86-1.11, P = 0.714). In clinical-stage specific sensitivity analyses, 5-year CSM rate was significantly worse for cT2N0M0 patients treated with TMT (HR: 1.52, 95% CI: 1.21-1.91, P < 0.001) than those treated with RC. For cT3-4N0M0 patients, there was no difference in CSM among the 2 approaches (HR: 0.98, 95% CI: 0.63-1.52, P = 0.900)., Conclusions: Our findings demonstrate an oncologic advantage of RC over TMT for cT2 MIBC patients. Conversely, we did not find a cancer-specific survival difference for cT3-T4 MIBC patients, regardless of treatment., Competing Interests: Declaration of competing interest None of the authors have any relevant disclosures, and none of the authors have any financial or nonfinancial interests that may be relevant to the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The European POUT III randomized controlled trial provided level-one evidence that adjuvant platinum-based chemotherapy is the standard of care following nephroureterectomy (RNU) for locally invasive or node-positive upper tract urothelial carcinoma. We aim to assess this European randomized controlled trial's generalizability (external validity) to a North American cohort, using a nationwide database., Materials and Methods: To compare trial patients with those seen in real-world practice, we simulated the trial inclusion criteria using data from the National Cancer Database (NCDB). We identified patients with histologically confirmed transitional cell carcinoma who underwent RNU. The available demographic characteristics of the NCDB cohort were compared with the POUT III trial cohort using Chi-squared test., Results: The NCDB cohort (n = 3,380) had a significantly higher proportion of older patients (age ≥ 80: 23.5% vs. 5%), and more males (68% vs. 56.2%) than the POUT cohort (Table 1, both p < 0.001). Additionally, the rate of advanced nodal disease was higher in the NCDB (N1 9.6%, N2 9.3%) than in the POUT (N1 6%, N2 3%) cohort (p < 0.001). A more extensive lymph node dissection was performed in NCDB vs. POUT patients (node≥10 10.9% vs. 3%, p < 0.001). Sensitivity analysis removing all subjects with a Charlson Comorbidity Index > 0 did not change the significance of any results., Conclusions: While the primary disease stage was similar, the rate of advanced nodal disease was significantly higher in NCDB, which might be explained partially by the more extensive lymph node dissection performed in the latter. These differences warrant caution when applying the POUT III findings to North American patients., Competing Interests: Declaration of competing interest The authors did not receive support from any organization for the submitted work. All authors have no relevant financial or non-financial interests to disclose. No funding was received to assist with the preparation of this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Lymph-vascular invasion (LVI) is recognized as an adverse pathological feature in patients with renal cell carcinoma (RCC). However, its impact on overall survival (OS) is not clear and scarcely addressed in the literature. We aimed to assess the prognostic ability of LVI as a predictor of OS in RCC patients using a large, North American cohort., Methods: We included 95,783 cM0 RCC patients, diagnosed between 2010 and 2015, who underwent partial or radical nephrectomy within the National Cancer Database. Kaplan-Meier curves and log-rank tests were used to depict and compare survival curves. Cox regression analysis tested the impact of LVI on OS, after adjusting for all available confounders., Results: Mean age (SD) was 59 (12), and most patients had pT1 stage (72.2%). Nodal status was pN0, pN1, and pNx, in 14.5%, 2.3%, and 83.3%, respectively. Overall, 9.0% of patients had LVI. The mean (SD) follow-up of the cohort was 39 months (24). At 5 years, OS was 65% in patients with LVI vs. 86% in patients without LVI (p<.0001). When patients were stratified based on nodal stage, these rates were 64% vs. 78% in pN0 patients, 31% vs. 41% in pN1 patients, and 69% vs. 87% in pNx patients (all P < 0.001). On multivariable analysis, and in comparison to patients without LVI, those with LVI had 1.37- (P < 0.001), 1.18- (P = 0.068), and 1.53-fold (P < 0.001) greater risk of death, when also harboring pN0, pN1, and pNx disease, respectively., Conclusions: Our findings are the first, to our best knowledge, to illustrate the clear detrimental impact of LVI on OS in surgically treated RCC patients. These findings might be useful in postoperative patient counseling and need to be accounted for when designing future clinical trials., Competing Interests: Declaration of Competing Interest None of the authors have any relevant disclosures, and none of the authors have any financial or non-financial interests that may be relevant to the submitted work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The benefits of lymph node dissection (LND) in surgically treated upper tract urothelial carcinoma (UTUC) patients who present with clinically positive nodes at diagnosis remain unclear. The aim of this study was to assess survival differences in cN+ patients who underwent radical nephroureterectomy (RNU) with LND vs. without LND., Methods: The National Cancer Database was used to identify a total number of 423 cN+ patients from 2004 to 2016 with UTUC that underwent RNU. Of the 423 patients, 310 received LND. Kaplan-Meier (KM) plots were used to estimate survival in cN+ patients who received RNU with LND vs. without. Cox proportional hazards regression tested the impact of LND status on overall survival (OS) after adjusting for all available covariates., Results: Median age of the patient population was 68 years (IQR 61-76), and 56.74% were male. Median follow-up was 1.8 years (IQR 0.9-3.5). For the entire cohort, the 2-year OS rate was 51.8%, and it was 52.1% vs. 51.1% in patients who underwent LND vs. not (log-rank p-value=0.2). On multivariable analysis, performing LND had no statistically significant impact on OS (HR 0.93 95%CI 0.696-1.235, P = 0.9). Repeating the analysis in patients who had exclusively cN1 (HR 0.76 95%CI 0.469-1.223, P = 0.26) or cN2/3 (HR 0.844 95%CI 0.556-1.28, P = 0.43) disease also failed to demonstrate a significant impact of LND on survival., Conclusion: In cN+ patients with UTUC, performing LND in addition to RNU at any clinical stage does not seem to have a significant impact on OS., Competing Interests: Conflicts of interest None of the authors have any relevant disclosures, and none of the authors have any financial or non-financial interests that may be relevant to the submitted work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess the prognostic ability of lymphovascular invasion (LVI) as a predictor of overall survival (OS)., Materials and Methods: We included 126,682 prostate cancer (CaP) cM0 patients who underwent radical prostatectomy with lymph node dissection between 2010 and 2015, within the National Cancer Database. Patients who received androgen deprivation therapy were included. Patients were divided into four sub-cohorts based on LVI and lymph node invasion (LNI) status: pL 0 N 0 , pL 1 N 0 , pL 0 N 1 , and pL 1 N 1 . Kaplan-Meier curves estimated OS and Cox-regression analysis tested the relationship between LVI and OS., Results: Median (IQR) age and PSA at diagnosis were 62 (57-66) years and 5.7 (4.5-8.9) ng/ml, respectively. Most patients had pT2 stage (68.5%), and pathological Gleason 3+4 (46.7%). 10.0% and 4.0% patients had LVI and LNI, respectively. Median follow-up was 42 months (27-58). At 5-years, OS was 96.5% in pL 0 N 0 patients vs 93.1% pL 1 N 0 patients vs 93.3% in pL 0 N 1 patients vs 86.6% pL 1 N 1 patients. LVI was an independent predictor of OS (hazard ratio [HR]:1.28). LVI showed interaction with LNI, as LVI was associated with a higher overall-mortality in patients with LNI (HR:1.66), than in patients without LNI (HR:1.22). (all P<0.0001) CONCLUSIONS: Our report highlights the detrimental impact of LVI on OS. Patients with LVI alone fared similarly to patients with LNI alone. Patients with both LVI and LNI had worse OS than those with only LVI or LNI, implying a synergetic detrimental interaction. Our findings demonstrate an important utility that LVI can provide in deciding patients' prognoses., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose, (Copyright © 2021. Published by Elsevier Inc.)

Introduction: The use of adjuvant radiotherapy (RT) after radical prostatectomy (RP) is very limited in prostate cancer patients mainly due to concerns for worsening of functional outcomes with early delivery of RT. We sought to test the impact of timing between RP and RT on adverse events rate., Methods: Using the Radiation Therapy Oncology Group (RTOG) 9601 trial cohort, we performed post hoc analysis of 760 men with biochemical recurrence after RP, who received subsequent RT. Bowel adverse events (rectal urgency, diarrhea, and hematochezia); bladder adverse events (urinary frequency, dysuria, hematuria, and incontinence); and new onset of erectile dysfunction were documented as acute (<90 days after starting RT) or chronic, at each visit, per trial protocol. Regression analysis tested the impact of time between RP and RT on the aforementioned adverse events, after adjusting for potential confounders., Results: The rate of acute bladder, acute bowel, late bladder, late bowel, and late impotence adverse events was, respectively, 49.3%, 60.9%, 61.2%, 48.8%, and 13.6% in patients with a time period between RP and RT ≤ 2.1 years (the median) vs. 47.5%, 63%, 59.1%, 47%, and 14.5% in patients with >2.1 years (all P > 0.5). At multivariable analysis, time from RP to RT was not an independent predictor of acute bladder (odds ratio [OR]: 1.002), acute bowel (OR: 1.024), chronic bladder (OR: 0.976), chronic bowel (OR: 1.023), and late impotence (OR: 1.031) adverse events (all P > 0.4)., Conclusions: There was no impact of timing between RP and RT on urinary, bowel, and erectile adverse events related to RT. Thus, our RTOG 9601 post hoc analysis challenges the current belief that early postsurgical RT compromises functional outcomes more than late RT and support additional research to evaluate the perceived benefit in terms of adverse effects by prolonging the time between RP and RT., (Copyright © 2019 Elsevier Inc. All rights reserved.)