The 2012 Briganti nomogram not only predicts lymph node involvement but also disease progression in surgically treated intermediate-risk prostate cancer patients with PSA <10 ng/mL, ISUP grade group 3, and clinical stage up to cT2b.

PURPOSE: We assessed the prognostic impact of the 2012 Briganti nomogram on prostate cancer (PCa) progression in intermediate-risk (IR) patients presenting with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b treated with robot assisted radical prostatectomy eventually associated with extended pelvic lymph node dissection. MATERIALS AND METHODS: From January 2013 to December 2021, data of surgically treated IR PCa patients were retrospectively evaluated. Only patients presenting with the above-mentioned features were considered. The 2012 Briganti nomogram was assessed either as a continuous and a categorical variable (up to the median, which was detected as 6%, vs. above the median). The association with PCa progression, defined as biochemical recurrence, and/or metastatic progression, was evaluated by Cox proportional hazard regression models. RESULTS: Overall, 147 patients were included. Compared to subjects with a nomogram score up to 6%, those presenting with a score above 6% were more likely to be younger, had larger/palpable tumors, presented with higher PSA, underwent tumor upgrading, harbored non-organ confined disease, and had positive surgical margins at final pathology. PCa progression, which occurred in 32 (21.7%) cases, was independently predicted by the 2012 Briganti nomogram both considered as a continuous (Hazard Ratio [HR]:1.04, 95% Confidence Interval [CI]:1.01-1.08;p=0.021), and a categorical variable (HR:2.32; 95%CI:1.11-4.87;p=0.026), even after adjustment for tumor upgrading. CONCLUSIONS: In IR PCa patients with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b, the 2012 Briganti nomogram independently predicts PCa progression. In this challenging subset of patients, this tool can identify prognostic subgroups, independently by upgrading issues.

Tumor upgrading among very favorable intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy: how can it impact the clinical course?

PURPOSE: We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression. METHODS: A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10 ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses. RESULTS: Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16-61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97-17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12-2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2. CONCLUSIONS: Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment.

The 2012 Briganti nomogram predicts disease progression in surgically treated intermediate-risk prostate cancer patients with favorable tumor grade group eventually associated with some adverse factors.

To evaluate the prognostic potential of the 2012 Briganti nomogram for pelvic lymph node invasion on disease progression after surgery in intermediate-risk (IR) prostate cancer (PCa) patients with favorable tumor grade (International Society of Urological Pathology grade group 1 or 2), eventually associated with adverse clinical features as PSA between 10 and 20 ng/mL and/or clinical stage T2b. All IR PCa patients treated with robot-assisted radical prostatectomy and eventually extended pelvic lymph node dissection at the Department of Urology of the Integrated University Hospital of Verona between 2013 and 2021, with the abovementioned features, and available follow-up were considered. The 2012 Briganti nomogram score was assessed both as a continuous and dichotomous variable, where a mean risk score of 4% was used a threshold. The independent predictor status of the nomogram score on disease progression defined as the occurrence of biochemical recurrence and/or metastatic progression was evaluated using the Cox regression analysis. Overall, 348 patients were enrolled in the study. Median (interquartile range) follow-up was 98 (83.5-112.4) months. At multivariable Cox regression analysis, PCa progression, which occurred in 65 (18.7%) cases, was independently predicted only by the 2012 Briganti nomogram score evaluated as a continuous variable, among all considered clinical features (HR 1.16; 95%CI 1.08-1.24; p < 0.001). In addition, patients presenting with a nomogram score ≥ 4% were more likely to experience disease progression even after adjustment for clinical (HR 2.22, 95%CI 1.02-4.79; p = 0.043) and pathological (HR 1.80; 95%CI 1.06-3.05; p = 0.031) factors. In the examined patient population, the 2012 Briganti nomogram predicted PCa progression after surgery. Accordingly, as the risk score increased, patients were more likely to progress, independently by the occurrence of adverse pathology in the surgical specimen. The 2012 Briganti nomogram score categorized according to the mean value allowed to identify prognostic subgroups.

Exploring the ADAM12 Expression in Clear Cell Renal Cell Carcinoma: A Radiogenomic Analysis on CT Imaging.

RATIONALE AND OBJECTIVES: Radiogenomics of clear cell renal cell carcinoma (ccRCC) has been developed thanks to the availability of genomic data, both gene expressions and gene mutations, obtained through the sequencing of ccRCC genome. These data are collected in the Cancer Genome Atlas (TCGA) Research Network-work. Disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) gene belongs to the family of genes coding for multidomain and multifunctional type I transmembrane proteins ADAMs. These proteins are fundamental for regulating cell adhesion and mediating proteolysis of a series of cell surface receptors and signal molecules extracellular domains. Recently, a correlation was detected between ADAM12 expression in ccRCC and tumor aggressiveness in terms of cell proliferation, migration, invasion, tumor progression, metastases, and poor prognosis, suggesting ADAM12 as a prognostic marker and therapeutic target in ccRCC. The computed tomography (CT) imaging phenotype of ADAM12 expression in ccRCC has never been studied. The aim of this study is to investigate the CT imaging phenotype of ADAM12 expression in ccRCC patients. MATERIALS AND METHODS: In this retrospective study, we enrolled 202 ccRCC patients divided into two groups: ccRCC patients with ADAM12 expression (n = 35) and ccRCC patients without ADAM12 expression (n = 167). Different imaging features were evaluated on CT scan at first diagnosis. The statistical significance threshold was set at p < 0.05. RESULTS: A statistically significant correlation was found with larger primary tumor size (p = 0.020), ill-defined tumor margins (p = 0.044), tumor necrosis (p = 0.011), and collecting system invasion (p = 0.014). CONCLUSION: This study demonstrates CT imaging features associated to ADAM12 expression in ccRCC. These results could help delve into ADAM12 gene status through CT approach and to further investigate towards the development of targeted therapies in ccRCC.

The impact of prognostic group classification on prostate cancer progression in intermediate-risk patients according to the European Association of Urology system: results in 479 patients treated with robot-assisted radical prostatectomy at a single tertiary referral center.

Background: Treatment outcomes in intermediate-risk prostate cancer (PCa) may be impaired by adverse pathology misclassification including tumor upgrading and upstaging. Clinical predictors of disease progression need to be improved in this category of patients. Objectives: To identify PCa prognostic factors to define prognostic groups in intermediate-risk patients treated with robot-assisted radical prostatectomy (RARP). Design: Data from 1143 patients undergoing RARP from January 2013 to October 2020 were collected: 901 subjects had available follow-up, of whom 479 were at intermediate risk. Methods: PCa progression was defined as biochemical recurrence and/or local recurrence and/or distant metastases. Study endpoints were evaluated by statistical methods including Cox's proportional hazards, Kaplan-Meyer survival curves, and binomial and multinomial logistic regression models. Results: After a median (interquartile range) of 35 months (15-57 months), 84 patients (17.5%) had disease progression, which was independently predicted by the percentage of biopsy-positive cores ⩾ 50% and the International Society of Urological Pathology (ISUP) grade group 3 for clinical factors and by ISUP > 2, positive surgical margins and pelvic lymph node invasion for pathological features. Patients were classified into clinical and pathological groups as favorable, unfavorable (one prognostic factor), and adverse (more than one prognostic factor). The risk of PCa progression increased with worsening prognosis through groups. A significant positive association was found between the two groups; consequently, as clinical prognosis worsened, the risk of detecting unfavorable and adverse pathological prognostic clusters increased in both unadjusted and adjusted models. Conclusion: The study identified factors predicting disease progression that allowed the computation of highly correlated prognostic groups. As the prognosis worsened, the risk of PCa progression increased. Intermediate-risk PCa needs more prognostic stratification for appropriate management.

A study on 479 patients looked at how prognostic group classification affects progression in patients with intermediate-risk prostate cancer treated with robot-assisted radical prostatectomy Prostate cancer is a serious health concern in men, and those with intermediate-risk prostate cancer may experience disease progression. Urologists use various methods to predict the risk of progression in these patients. However, sometimes the predictions are not accurate. Therefore, researchers conducted a study to identify factors that could help predict disease progression in patients with intermediate-risk prostate cancer who underwent robot-assisted surgery. This study on 479 patients found that a percentage of biopsy-positive cores ⩾ 50% and the International Society of Urological Pathology (ISUP) grade group 3 were predictive factors of disease progression. Additionally, factors like ISUP > 2, positive surgical margins, and pelvic lymph node invasion also predicted disease progression. Patients were classified into three groups based on their clinical and pathological features: favorable, unfavorable (one negative prognostic factor), and adverse (more than one negative prognostic factor). The risk of prostate cancer progression increased as the prognosis worsened through these groups. The study concluded that a more accurate stratification of intermediate-risk prostate cancer patients is needed to manage the disease effectively.

CT-Based Radiogenomics of P4HA3 Expression in Clear Cell Renal Cell Carcinoma.

RATIONALE AND OBJECTIVES: The sequencing of the renal cell carcinoma (RCC) genome identified several mutations with prognostic significance. Genomic analysis, collected in The Cancer Genome Atlas Research Network, revealed several clear cell renal cell carcinoma (ccRCC) gene mutations and gene expressions. Radiogenomics is a new branch of diagnostic imaging based on the association between imaging phenotypes and genomics of diseases. P4HA3 expression has recently been shown to correlate with increased aggressiveness of ccRCC, with poor prognosis, proliferation, migration, invasion, and metastases, suggesting P4HA3 as a prognostic marker and therapeutic target in ccRCC. The aim of this study is to investigate the computed tomography (CT) imaging phenotype of P4HA3 expression in ccRCC patients. MATERIALS AND METHODS: In this retrospective study we enrolled 196 ccRCC patients divided into two groups: ccRCC patients with P4HA3 expression (n = 13) and ccRCC patients without P4HA3 expression (n = 183). Several imaging features were evaluated on preoperative CT scan. The statistical significance threshold was set at P < .05. RESULTS: A statistically significant association was found with larger primary tumor size (P = .033), tumor infiltration (P = .023), ill-defined tumor margins (P = .025), and advanced tumor stage American Joint Committee of Cancer (P = .014). CONCLUSION: This study demonstrates CT imaging features associated with P4HA3 expression in ccRCC. These results could contribute to better understand P4HA3 expression with a noninvasive approach and could be applied to the development of targeted therapies.

Positive independent association between preoperative endogenous testosterone density and tumor load density in surgical specimen of patients undergoing radical prostatectomy.

OBJECTIVE: To evaluate the influence of endogenous testosterone density (ETD) and tumor load density (TLD) in the surgical specimen of prostate cancer (PCa) patients. METHODS: ETD was assessed as the ratio of endogenous testosterone (ET) to prostate volume (PV). TLD was calculated as the ratio of tumor load (TL) to prostate weight. Preoperative prostate-specific antigen relative densities (PSAD) and percentage of biopsy-positive cores (BPCD) were also assessed. The association of high TLD (above the first quartile) with clinical and pathological factors was assessed by the logistic regression model (univariate and multivariate analysis). RESULTS: Between November 2014 and December 2019, ET was measured in 805 cases treated with radical prostatectomy (RP). Median (IQR) of ET and ETD was 412 (321.4-519 ng/dL) and 9.8 (6.8-14.4 ng/(dLxmL)) as well as for TL and TLD was 20 (10-30%) and 0.33 (0.17-0.58%/gr), respectively. As a result, high TLD was detected in 75% of cases. A positive independent association was found between high TLD and ETD. Accordingly, as ETD levels increased, the risk of detecting high TLD in the surgical specimen increased, regardless of PSAD and BPCD. CONCLUSIONS: At diagnosis of PCa, a positive independent association was found between ETD and risk of high TLD. Subjects with increasing ETD levels were more likely to have high TLD, associated with unfavorable pathology features. The positive association between ETD and TLD in the prostate microenvironment might adversely influence PCa's natural history.

Differences in Survival of Clear Cell Metastatic Renal Cell Carcinoma According to Partial vs. Radical Cytoreductive Nephrectomy.

BACKGROUND: It is unknown whether previously reported other-cause mortality (OCM) advantage of partial cytoreductive nephrectomy (PCN) vs. radical cytoreductive nephrectomy (RCN) still applies to contemporary clear cell metastatic renal cell carcinoma (ccmRCC) patients. MATERIALS AND METHODS: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify ccmRCC patients treated with PCN and RCN. Temporal trends of PCN rates within the SEER database were tabulated. After propensity score matching (PSM), cumulative incidence plots depicted 5-year OCM and cancer-specific mortality (CSM) of PCN and RCN patients. Multivariable Cox regression models tested for differences between PCN vs. RCN. RESULTS: Of 5149 study patients, 237 (5%) underwent PCN vs. 4912 (95%) RCN. In the SEER database 2004 to 2019, rates of PCN in ccmRCC patients increased from 3.0% to 8.0% (estimated annual percent change [EAPC]: 3.0%; P = .04). After PSM, 5-year OCM rates were 2.4 vs. 7.5% for respectively PCN vs. RCN patients (P = .036). 5-year CSM rates were 50.8 vs. 53.6% for respectively PCN and RCN patients (P = .57). In multivariable Cox regression models, PCN was associated with lower OCM (Hazard Ratio (HR): 0.39; 95% confidence interval (CI): 0.18-0.84; P = .02) but did not affect CSM rates (HR: 0.99; 95% CI: 0.76-1.29; P = .96). CONCLUSIONS: We confirm the existence of OCM advantage after PCN vs. RCN in contemporary ccmRCC patients.

Platelet-rich plasma intracavernosal injections for the treatment of primary organic erectile dysfunction: a systematic review and meta-analysis of contemporary controlled studies.

We aim to summarize the latest evidence on platelet-rich plasma (PRP) intracavernosal injections efficacy in men affected by primary organic erectile dysfunction (ED). We reviewed the literature for randomized controlled trials (RCTs) or prospective and retrospective comparative studies evaluating PRP alone or in combination for ED treatment. A comprehensive search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov was performed for English language full-text articles or conference abstracts. A qualitative and quantitative data synthesis was provided. Overall, seven records were included: three RCTs evaluated PRP vs. placebo, one study separately tested PRP and low-intensity shock wave therapy (Li-SWT), three studies compared Li-SWT or low-intensity pulsed ultrasound alone with their combination with PRP. Of 641 included patients, 320 received PRP. Despite the heterogeneity among inclusion criteria, dose and protocol of PRP administration, and outcomes measured, most studies independently reported better sexual outcomes in patients who received PRP, without significant severe side effects. In meta-analysis, where only placebo-controlled studies were included, patients treated with PRP showed higher International Index of Erectile Function (erectile function domain) score compared to patients who received placebo: pooled mean difference (95% Confidence Interval) of 2.99 (1.86, 4.13) after 1 month (209 patients) vs. 2.85 (1.61, 4.09) after 3 months (204 patients) vs. 3.21 (1.82, 4.60) after 6 months (199 patients) of follow-up. In men affected by primary organic ED, PRP intracavernosal injections demonstrated an objective improvement or at least a tendency in erectile function recovery. Patient numbers, and the short-term follow-up may limit the generalizability of these observations. High quality, large-scale, and standardized controlled trials are needed before recommending its definitive use in clinical practice.

Radiogenomic Features of GIMAP Family Genes in Clear Cell Renal Cell Carcinoma: An Observational Study on CT Images.

GTPases of immunity-associated proteins (GIMAP) genes include seven functional genes and a pseudogene. Most of the GIMAPs have a role in the maintenance and development of lymphocytes. GIMAPs could inhibit the development of tumors by increasing the amount and antitumor activity of infiltrating immunocytes. Knowledge of key factors that affect the tumor immune microenvironment for predicting the efficacy of immunotherapy and establishing new targets in ccRCC is of great importance. A computed tomography (CT)-based radiogenomic approach was used to detect the imaging phenotypic features of GIMAP family gene expression in ccRCC. In this retrospective study we enrolled 193 ccRCC patients divided into two groups: ccRCC patients with GIMAP expression (n = 52) and ccRCC patients without GIMAP expression (n = 141). Several imaging features were evaluated on preoperative CT scan. A statistically significant correlation was found with absence of endophytic growth pattern (p = 0.049), tumor infiltration (p = 0.005), advanced age (p = 0.018), and high Fuhrman grade (p = 0.024). This study demonstrates CT imaging features of GIMAP expression in ccRCC. These results could allow the collection of data on GIMAP expression through a CT-approach and could be used for the development of a targeted therapy.

Regional differences in stage distribution and rates of treatment for adrenocortical carcinoma across United States SEER registries.

BACKGROUND: We tested for regional differences across United States (US) in rates of adrenalectomy, systemic therapy, and adrenalectomy and systemic therapy combination for adrenocortical carcinoma (ACC) patients. We hypothesized that no differences exist, especially after accounting for baseline patient and tumor characteristics. METHODS: Within Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), 1275 ACC patients were identified. Distribution of patient age, tumor size, ENSAT (European Network for the Study of Adrenal Tumors) stages, and treatments were tabulated and graphically displayed, according to nine geographical registries, corresponding to the population of specific states, cities or macro areas of the US on which the data are based on. Multinomial models predicted treatment probability for each patient according to registries. RESULTS: Patients count according to registries ranged from 62 to 509. Differences across registries existed for age (range 54-59 years; P=0.4), tumor size (8.5-11.0 cm; P=0.2), ENSAT stage (1-11% vs. 17-35% vs. 18-32% vs. 24-44%, in respectively ENSAT stage I, II, III, and IV), and treatment distribution (35-53% vs. 5-21% vs. 23-42%, in respectively adrenalectomy, systemic therapy, and adrenalectomy and systemic therapy combination; P=0.039). After adjustment for age, stage and year of diagnosis, clinically meaningful residual differences across registries remained for adrenalectomy (33-54%), systemic therapy (4-19%), and adrenalectomy and systemic therapy combination (20-38%). However, most variability originated from registries with smallest sample sizes. CONCLUSIONS: We identified important variability in ACC treatment according to SEER geographical registries, even after considering baseline patient and tumor characteristics. These findings may be indicative of differences in quality of care or expertise in ACC management.

Prognostic impact of palpable prostate tumors on disease progression after robot-assisted radical prostatectomy: a single-center experience.

OBJECTIVE: This study aimed to evaluate the impact of palpable prostate tumors on digital rectal exam (DRE) on the disease progression of prostate cancer (PCa) treated with RARP surgery in a tertiary referral center. MATERIALS AND METHODS: Overall, 901 patients were evaluated in a period ranging from January 2013 to October 2020. In the surgical specimen, unfavorable pathology included ISUP grade group ≥3, seminal vesicle invasion (SVI), and pelvic lymph node invasion (PLNI). Disease progression was defined as the occurrence of biochemical recurrence and/or local recurrence and/or distant metastases; its association with the primary endpoint was evaluated by Cox's proportional model. RESULTS: Palpable prostate tumors were detected in 359 (39.8%) patients. The overall median (IQR) follow-up was 40 months (17-59). PCa progressed in 159 cases (17.6%). Nodularity or induration of the prostate at DRE was significantly associated with features of unfavorable pathology, increased risk of PCa progression (hazard ratio, HR = 1.902; 95% CI: 1.389-2.605; p < 0.0001) and, on multivariable analysis, was an independent prognostic factor for disease progression after adjusting for clinical and pathological variables. CONCLUSIONS: Prostate tumors presenting with an abnormal DRE finding have an independent adverse outcome for disease progression after PCa surgery. They provide also independent prognostic information, as they may be more aggressive than impalpable PCa.

Racial/ethnic disparities in the distribution and effect of type and number of high-risk criteria on mortality in prostate cancer patients treated with radiotherapy.

Objective: To assess differences in the distribution of type and number of D'Amico high-risk criteria (DHRCs) according to race/ethnicity (R/E) and their effect on cancer-specific mortality (CSM) in prostate cancer (PCa) patients treated with external beam radiotherapy (RT). Methods: In the SEER database (2004-2016), we identified 31,002 PCa patients treated with RT with at least one DHRCs, namely PSA >20 ng/dL, biopsy Gleason Grade Group 4-5, and clinical T stage ≥T2c. Competing risks regression (CRR) model tested the association between DHRCs and 5-year CSM in all R/E subgroups. Results: Of 31,002 patients, 20,894 (67%) were Caucasian, 5256 (17%) were African American, 2868 (9.3%) were Hispanic-Latino, and 1984 (6.4%) were Asian. The distributions of individual DHRCs and combinations of two DHRCs differed according to R/E, but not for the combination of three DHRCs. The effect related to the presence of a single DHRC, and combinations of two or three DHRCs on absolute CSM rates was lowest in Asians (1.2-6.8%), followed by in African Americans (2.3-12.2%) and Caucasians (2.3-12.1%), and highest in Hispanic/Latinos (1.7-13.8%). However, the opposite effect was observed in CRR, where hazard ratios were highest in Asians vs. other R/Es: Asians 1.00-2.59 vs. others 0.5-1.83 for one DHRC, Asians 3.4-4.75 vs. others 0.66-3.66 for two DHRCs, and Asians 7.22 vs. others 3.03-4.99 for all three DHRCs. Conclusions: R/E affects the proportions of DHRCs. Moreover, within the four examined R/E groups, the effect of DHRCs on absolute and relative CSM metrics also differed. Therefore, R/E-specific considerations may be warranted in high-risk PCa patients treated with RT.

Advanced age is an independent prognostic factor of disease progression in high-risk prostate cancer: results in 180 patients treated with robot-assisted radical prostatectomy and extended pelvic lymph node dissection in a tertiary referral center.

OBJECTIVES: This study aimed to assess more clinical and pathological factors associated with prostate cancer (PCa) progression in high-risk PCa patients treated primarily with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) in a tertiary referral center. MATERIALS AND METHODS: In a period ranging from January 2013 to October 2020, RARP and ePLND were performed on 180 high-risk patients at Azienda Ospedaliera Universitaria Integrata of Verona (Italy). PCa progression was defined as biochemical recurrence/persistence and/or local recurrence and/or distant metastases. Statistical methods evaluated study endpoints, including Cox's proportional hazards, Kaplan-Meyer survival curves, and binomial logistic regression models. RESULTS: The median age of included patients was 66.5 [62-71] years. Disease progression occurred in 55 patients (30.6%), who were more likely to have advanced age, palpable tumors, and unfavorable pathologic features, including high tumor grade, stage, and pelvic lymph node invasion (PLNI). On multivariate analysis, PCa progression was predicted by advanced age (≥ 70 years) (HR = 2.183; 95% CI = 1.089-4377, p = 0.028), palpable tumors (HR = 3.113; 95% CI = 1.499-6.465), p = 0.002), and PLNI (HR = 2.945; 95% CI = 1.441-6.018, p = 0.003), which were associated with clinical standard factors defining high-risk PCa. Age had a negative prognostic impact on elderly patients, who were less likely to have palpable tumors but more likely to have high-grade tumors. CONCLUSIONS: High-risk PCa progression was independently predicted by advanced age, palpable tumors, and PLNI, which is associated with standard clinical prognostic factors. Consequently, with increasing age, the prognosis is worse in elderly patients, who represent an unfavorable age group that needs extensive counseling for appropriate and personalized management decisions.

Impairment in Activities of Daily Living Assessed by the Barthel Index Predicts Adverse Oncological Outcomes After Radical Cystectomy for Bladder Cancer.

INTRODUCTION: We tested the association between functional impairment in activities of daily living (ADL) assessed through the Barthel Index (BI), and oncological outcomes following radical cystectomy (RC) for bladder cancer (BCa). PATIENTS AND METHODS: We retrospectively analyzed data of 262 clinically nonmetastatic BCa patients, who underwent RC between 2015 and 2022, with available follow-up. According to preoperative BI, patients were divided in 2 groups: BI ≤90 (moderate/severe/total dependency in ADL) versus BI 95 to 100 (slight dependency/independency in ADL). Kaplan-Meier plots compared disease recurrence (DR)-, cancer-specific mortality (CSM)-, and overall mortality (OM)-free survival according to established categories. Multivariable Cox regression models tested the BI as an independent predictor of oncological outcomes. RESULTS: According to the BI, the patient cohort was distributed as follows: 19% (n = 50) BI ≤90 versus 81% (n = 212) BI 95-100. Compared to patients with BI 95 to 100, patients with BI ≤90 were less likely to receive intravesical immuno- or chemotherapy (18% vs. 34%, p = .028), and more frequently underwent less complex urinary diversion as ureterocutaneostomy (36% vs. 9%, p < .001), or harbored muscle-invasive BCa at final pathology (72% vs. 56%, p = .043). In multivariable Cox regression models adjusted for age, ASA physical status score, pathological T and N stage, and surgical margins status, BI ≤90 independently predicted higher DR (HR [hazard ratio]:2.00, 95%CI [confidence interval]:1.21-3.30, p = .007), CSM (HR:2.70, 95%CI:1.48-4.90, p = .001), and OM (HR:2.09, 95%CI:1.28-3.43, p = .003). CONCLUSION: Preoperative impairment in ADL was associated with adverse oncological outcomes following RC for BCa. The integration of the BI into clinical practice may improve the risk assessment of BCa patients candidates to RC.

Age represents the main driver of surgical decision making in patients candidate to radical cystectomy.

BACKGROUND AND OBJECTIVES: Age might influence the choice of surgical approach, type of urinary diversion (UD) and lymph node dissection (LND) in patients candidate to radical cystectomy (RC) for urothelial bladder cancer (UBC). Similarly, age may enhance surgical morbidity and worsen perioperative outcomes. We tested the impact of age (octogenarian vs. younger patients) on surgical decision making and peri- and postoperative outcomes of RC. METHODS: Non-metastatic muscle-invasive UBC patients treated with RC at 18 high-volume European institutions between 2006 and 2021 were identified and stratified according to age (≥80 vs. <80 years). Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology guidelines recommendations were accomplished in collection and reporting of, respectively, intraoperative and postoperative complications. Multivariable logistic regression models (MVA) tested the impact of age on outcomes of interest. Sensitivity analyses after 1:3 propensity score matching were performed. RESULTS: Of 1955 overall patients, 251 (13%) were ≥80-year-old. Minimally invasive RC was performed in 18% and 40% of octogenarian and younger patients, respectively (p < 0.001). UD without bowel manipulation (ureterocutaneostomy, UCS) was performed in 31% and 7% of octogenarian and younger patients (p < 0.001). LND was delivered to 81% and 93% of octogenarian and younger patients (p < 0.001). At MVA, age ≥80 years independently predicted open approach (odds ratio [OR]: 1.55), UCS (OR: 3.70), and omission of LND (OR: 0.41; all p ≤ 0.02). Compared to their younger counterparts, octogenarian patients experienced higher rates of intraoperative (8% vs. 4%, p = 0.04) but not of postoperative complications (64% vs. 61%, p = 0.07). At MVA, age ≥80 years was not an independent predictor of length of stay, intraoperative or postoperative transfusions and complications, and readmissions (all p values >0.1). These results were replicated in sensitivity analyses. CONCLUSIONS: Age ≥80 years does not independently portend worse surgical outcomes for RC. However, octogenarians are unreasonably more likely to receive open approach and UCS diversion, and less likely to undergo LND.

Cancer-specific mortality free survival rates in non-metastatic non-clear cell renal carcinoma patients at intermediate/high risk of recurrence.

BACKGROUND: To date, five trials testing the effect of adjuvant systemic therapy in surgically treated non-metastatic renal cell carcinoma included patients with non-clear cell histology. We tested the effect of papillary vs. chromophobe histological subtype, stage, and grade on 10-year cancer-specific survival, in patients eligible for ≥1 such trial. METHODS: We identified patients meeting ASSURE, SORCE, EVEREST, PROSPER, or RAMPART trial inclusion criteria in the SEER (2000-2018) database. Kaplan-Meier analyses estimated 10-year survival rates and multivariable Cox regression models tested for the independent predictor status of histological subtype, stage, and grade. RESULTS: We identified 5465 (68%) papillary and 2562 (32%) chromophobe renal cell carcinoma patients. Cancer-specific survival rates at 10 years were 77% in papillary vs. 90% in chromophobe. In multivariable Cox regression models applied to papillary patients, cancer-specific mortality independent predictor status was reached for T3G3-4 (HR 2.9), T4Gany (HR 3.4), TanyN1G1-2 (HR 3.1), and TanyN1G3-4 (HR 8.0, P<0.001), relative to T1/2Gany. In multivariable Cox regression models applied to chromophobe patients, mortality independent predictor status was reached for T3G3-4 (HR 3.6), T4Gany (HR 14.0), TanyN1G1-2 (HR 5.7), and TanyN1G3-4 (HR 15.0, P<0.001), relative to T1/2Gany. CONCLUSIONS: In surgically treated non-metastatic intermediate/high-risk renal cell carcinoma patients, papillary histologic subtype exhibited worse cancer-specific survival than chromophobe histologic subtype. Although stage and grade represented independent predictors in both histological subtype groups, the magnitude of their effect was invariably worse in chromophobe than in papillary patients. In consequence, papillary and chromophobe patients should be considered separate entities instead of being combined under the non-clear cell designation.

African American vs Caucasian race/ethnicity in adrenocortical carcinoma patients.

In some primaries, African American race/ethnicity predisposes to higher stage and worse survival. We tested for differences in cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with adrenocortical carcinoma (ACC) according to African American vs Caucasian race/ethnicity. We hypothesized that African Americans present with higher tumor stage and grade, do not receive the same treatment, and experience worse oncological outcomes than Caucasians. Within Surveillance, Epidemiology, and End Results database, we identified 1016 ACC patients: 123 (12.1%) African Americans vs 893 (87.9%) Caucasians. Propensity score matching (PSM) (age, sex, marital status, grade, T, N, and M stages, and treatment type), Poisson-smoothed cumulative incidence plots, and competing risk regression (CRR) were used. Compared to Caucasians, African Americans were more frequently unmarried (56.9% vs 35.5%, P < 0.001). No clinically meaningful or statistically significant differences were observed for age, grade, T, N, and M stages, as well as treatment type (all P > 0.05). After PSM (1:4), 123 African Americans and 492 Caucasians remained and were included in CRR analysis. In multivariable CRR models, CSM and OCM rates were not different between the two race/ethnicities (hazard ratio: 0.84, P = 0.3). In African Americans, 5-year CSM rates were 31.2% and 75.3% in European Network for the Study of Adrenal Tumors (ENSAT) stages I-II and III-IV, respectively vs 32.9% and 75.4% in Caucasians. Overall 5-year OCM rates were 11.0% vs 10.1% in respectively African Americans and Caucasians. Unlike other primaries, in ACC, African American race/ethnicity is not associated with higher disease stage at initial diagnosis or worse survival.

Preoperative endogenous total testosterone predicts prostate cancer progression: results in 580 consecutive patients treated with robot assisted radical prostatectomy for clinically localized disease.

PURPOSE: To test the role of endogenous total testosterone (ETT) as a predictor of prostate cancer (PCa) progression in patients treated with robot assisted radical prostatectomy for clinically localized disease. METHODS: Between November 2014 and December 2019, 580 consecutive patients were evaluated. Preoperative ETT levels were classified as ≤ 350 ng/dL vs. > 350 ng/dL. The associations between ETT levels and the risk of PCa progression, defined as any event of biochemical recurrence and/or local recurrence and/or distant metastases, or other clinical and pathological factors were evaluated by regression analyses. RESULTS: Preoperative ETT levels resulted ≤ 350 ng/dL in 173 (29.8%) patients. Disease progression occurred in 101 (17.1%) cases. Progressing patients were more likely to present with PSA levels > 10 ng/mL, as well as with unfavorable tumor grade (ISUP 4-5) and stage (pT3b) at final pathology, but less likely to have ETT levels ≤ 350 ng/mL. On clinical multivariable Cox regression models, ETT ≤ 350 ng/mL exhibited a statistically significant protective effect on tumor progression (hazard ratio: 0.57, p = 0.013). Subjects presenting with ETT levels ≤ 350 ng/mL were less likely to harbor ISUP 4-5 tumor grade either at biopsy (odds ratio [OR]: 0.46, p = 0.028) or final pathology (OR: 0.45, p = 0.032). CONCLUSIONS: At PCa diagnosis, ETT, which associates with ISUP tumor grade, is an independent predictor of disease progression. Accordingly, as ETT decreases to levels ≤ 350 ng/dL, the risk of unfavorable tumor grade decreases, and a more favorable prognosis is expected. Preoperative ETT levels may allow further patient stratification along prognostic risk groups.