Predicting global QoL after orthotopic neobladder or ileal conduit diversion: nomogram development

Introduction - Quality of life (QoL) outcomes in patients undergoing radical cystectomy (RC) with orthotopic neobladder (ONB) or ileal conduit (IC) have been extensively investigated. However, a general lack of consensus on QoL’s predictive factors exists. The aim of the study was to develop a nomogram using preoperative parameters to predict global QoL outcome in patients with localized muscle-invasive bladder cancer (MIBC) undergoing RC with ONB or IC urinary diversion (UD). MethodsA cohort of 319 patients who underwent RC and ONB or IC were retrospectively enrolled. Multivariable linear regression analyses were used to predict the global QoL score of the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), according to the patient characteristics and UD. A nomogram was developed and internally validated. Results Patients’ data in the two study groups significantly differed with regard to comorbidity profiles (chronic cardiac failure, p < 0.001; chronic kidney disease, p < 0.01; hypertension, p < 0.03; diabetic disease, p = 0.02; chronic arthritis, p = 0.02). A multivariable model that included patient age at surgery, UD, chronic cardiac disease, and peripheral vascular disease represented the basis for the nomogram. The calibration plot of the prediction model showed a systematic overestimation of the predicted global QoL score over the observed scores, with a slight underestimation for observed global QoL scores between 57 and 72. After performing leave-one-out cross-validation, the root mean square error (RMSE) emerged as 24.0. Discussion/conclusionA novel nomogram based completely on known preoperative factors was developed for patients with MIBC undergoing RC to predict a mid-term QoL outcome

The Complex Interplay between Serum Testosterone and the Clinical Course of Coronavirus Disease 19 Pandemic: A Systematic Review of Clinical and Preclinical Evidence

Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARSCoV- 2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARSCoV- 2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensinconverting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes (i.e., admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism

Contemporary rates of pathological features and mortality for adenocarcinoma of the urinary bladder in the USA.

OBJECTIVES: To examine contemporary rates of pathological features and mortality for adenocarcinoma of the urinary bladder in the USA using population-based data analysis. METHODS: We relied on 10 024 patients with non-metastatic bladder cancer diagnosed between 2004 and 2013 within the Surveillance, Epidemiology and End Results registries. Logistic regression analyses focused on grade and stage. Kaplan-Meier analyses assessed cancer-specific mortality rates in adenocarcinoma and urothelial carcinoma of the bladder. Cox regression analyses assessed the impact of histological subtype on cancer-specific mortality. RESULTS: Overall, 215 (2.1%) adenocarcinoma and 9809 (97.9%) urothelial carcinoma patients were identified. The rate of non-organ-confined disease was higher in adenocarcinoma (64.7% vs 50.8%, P \u3c 0.001). In multivariable logistic regression analyses, adenocarcinoma patients had a 2.2-fold higher risk of harboring non-organ-confined disease (95% confidence interval 1.7-3.0; P \u3c 0.001) than urothelial carcinoma patients. Cancer-specific mortality-free survival rates were lower in adenocarcinoma (P \u3c 0.01). This disadvantage only applied to non-organ-confined disease (P = 0.044), and not to organ-confined disease (P = 0.9). In multivariable Cox regression analyses, adenocarcinoma conferred a 1.3-fold higher rate of cancer-specific mortality (hazard ratio 1.30, 95% confidence interval 1.05-1.60; P = 0.01). Among adenocarcinoma patients, 30.7% harbored signet-ring cell adenocarcinoma and portended particularly poor cancer-specific mortality rates. CONCLUSIONS: In bladder cancer, adenocarcinoma presents at higher stages than urothelial carcinoma. However, cancer-specific mortality rates do not differ. A more unfavorable stage at diagnosis and higher cancer-specific mortality apply to the signet-ring cell variant

North American Population-Based Validation of the National Comprehensive Cancer Network Practice Guideline Recommendation of Pelvic Lymphadenectomy in Contemporary Prostate Cancer.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend a pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) if a nomogram predicted risk of lymph node invasion (LNI) is ≥2%. We examined this and other thresholds, including nomogram validation. METHODS: We examined records of 26,713 patients treated with RP and PLND between 2010 and 2013, within the Surveillance, Epidemiology, and End Results database. Nomogram thresholds of 2-5% were tested and external validation was performed. RESULTS: LNI was recorded in 4.7% of patients. Nomogram accuracy was 80.4% and maintained minimum accuracy of 75.6% in subgroup analyses, according to age, race, and nodal yield \u3e10. With the NCCN recommended 2% nomogram threshold, PLND could be avoided in 22.3% of patients at the expense of missing 3.0% of individuals with LNI. Alternative thresholds of 3%, 4%, and 5% yielded respective PLND avoidance rates of 60.4%, 71.0%, and 79.8% at the expense of missing 17.8%, 27.2%, and 36.6% of patients with LNI. NCCN cut-off recommendation was best satisfied with a threshold of \u3c2.6%, at which PLND could be avoided in 13,234 patients (49.5%) versus missing 141 patients with LNI (11.2%). CONCLUSION: NCCN LNI nomogram remains accurate in contemporary patients. However, the 2% threshold appears to be too strict, since only 22.3% of PLNDs can be avoided, instead of the stipulated 47.7%. The optimal 2.6% threshold allows a higher rate of PLND avoidance (49.5%), at the cost of 11.2% missed instances of LNI, as recommended by NCCN guidelines. PATIENT SUMMARY. External validation in contemporary SEER prostate cancer patients showed that the NCCN nomogram remains accurate for predicting lymph node invasion and seems to be optimal at an alternative 2.6% threshold, with best ratio of avoided pelvic lymph node dissections (49.5%) and missed LNIs (11.2%), as recommended by NCCN guideline

Population-Based External Validation of the Updated 2012 Partin Tables in Contemporary North American Prostate Cancer Patients

OBJECTIVE: To externally validate the updated 2012 Partin Tables in contemporary North American patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa) at community institutions. MATERIALS AND METHODS: We examined records of 25,254 patients treated with RP and pelvic lymph node dissection (PLND) between 2010 and 2013, within the surveillance, epidemiology, and end results database. The ROC derived AUC assessed discriminant properties of the updated 2012 Partin Tables of organ confined disease (OC), extracapsular extension (ECE), seminal vesical invasion (SVI), and lymph node invasion (LNI). Calibration plots focused on calibration between predicted and observed rates. RESULTS: Proportions of OC, ECE, SVI, and LNI at RP were 69.8%, 18.4%, 7.4%, and 4.4%, respectively. Accuracy for prediction of OC, ECE, SVI, and LNI was 70.4%, 59.9%, 72.9%, and 77.1%, respectively. In subgroup analyses in patients with nodal yield \u3e10, accuracy for LNI prediction was 76.0%. Subgroup analyses in elderly patients and in African American patients revealed decreased accuracy for prediction of all four endpoints. Last but not least, SVI and LNI calibration plots showed excellent agreement, versus good agreement for OC (maximum underestimation of 10%) and poor agreement for ECE (maximum overestimation of 12%). CONCLUSION: Taken together, the updated 2012 Partin Tables can be unequivocally endorsed for prediction of OC, SVI, and LNI in community-based patients with localized PCa. Conversely, ECE predictions failed to reach the minimum accuracy requirements of 70%. Prostate 77:105-113, 2017. © 2016 Wiley Periodicals, Inc

Local Therapy Improves Survival in Metastatic Prostate Cancer

BACKGROUND: Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT). OBJECTIVE: To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results database (2004-2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses. RESULTS AND LIMITATIONS: Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT (n=474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32-0.50) versus NLT (n=1896). In MVA CRR after PSM, RP (n=161) results in lower CSM (SHR 0.59, 95% CI 0.35-0.99) versus RT (n=161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR=5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective. CONCLUSIONS: In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits. PATIENT SUMMARY: Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy