The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data.

BACKGROUND AND AIM: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. PATIENTS AND METHODS: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. RESULTS: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence.

Kidney stone disease (KSD) is one of the most common urological diseases. The incidence of kidney stones has increased dramatically in the last few decades. Kidney stones are mineral deposits in the calyces or the pelvis, free or attached to the renal papillae. They contain crystals and organic components, and they are made when urine is supersaturated with minerals. Calcium-containing stones are the most common, with calcium oxalate as the main component of most stones. However, many of these form on a calcium phosphate matrix called Randall's plaque, which is found on the surface of the kidney papilla. The etiology is multifactorial, and the recurrence rate is as high as 50% within 5 years after the first stone onset. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more effective drugs. This review aims to understand the pathophysiology and the main molecular mechanisms known to date to prevent recurrences, which requires behavioral and nutritional interventions, as well as pharmacological treatments that are specific to the type of stone.

Time to progression is the main predictor of survival in patients with high-risk nonmuscle invasive bladder cancer: Results from a machine learning-based analysis of a large multi-institutional database.

BACKGROUND: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints. METHODS: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality. RESULTS: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference). CONCLUSION: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design.

Transurethral prostate surgery in prostate cancer patients: A population-based comparative analysis of complication and mortality rates.

Objective: Prostate cancer (PCa) patients might experience lower urinary tract symptoms as those diagnosed with benign prostatic hyperplasia (BPH). Some of them might be treated for their lower urinary tract symptoms instead of PCa. We aimed to test the effect of PCa versus BPH on surgical outcomes after transurethral prostate surgery, namely complication and mortality rates. Methods: Within the American College of Surgeons National Surgical Quality Improvement Program database (2011-2016), we identified patients who underwent transurethral resection of the prostate, photoselective vaporization, or laser enucleation. Patients were stratified according to postoperative diagnosis (PCa vs. BPH). Univariable and multivariable logistic regression models evaluated the predictors of perioperative morbidity and mortality. A formal test of interaction between diagnosis and surgical technique used was performed. Results: Overall, 34 542 patients were included. Of all, 2008 (5.8%) had a diagnosis of PCa. The multivariable logistic regression model failed to show statistically significant higher rates of postoperative complications in PCa patients (odds ratio: 0.9, 95% confidence interval: 0.7-1.1; p=0.252). Moreover, similar rates of perioperative mortality (p=0.255), major acute cardiovascular events (p=0.581), transfusions (p=0.933), and length of stay of more than or equal to 30 days (p=0.174) were found. Additionally, all tests failed to show an interaction between post-operative diagnosis and surgical technique used. Conclusion: Patients diagnosed with PCa do not experience higher perioperative morbidity or mortality after transurethral prostate surgery when compared to their BPH counterparts. Moreover, the diagnosis seems to not influence surgical technique outcomes.

Advanced Age Impacts Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

INTRODUCTION: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes. PATIENTS AND METHODS: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant. RESULTS: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer). CONCLUSION: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group.

Retzius-Sparing Robotic-Assisted Prostatectomy: Technical Challenges for Surgeons and Key Prospective Refinements.

Robotic-assisted radical prostatectomy (RARP) is the gold standard for localized prostate cancer. Several RARP approaches were developed and described over the years, aimed at improving oncological and functional outcomes. In 2010, Galfano et al described a new RARP technique, known as Retzius-sparing RARP (RS-RARP), a posterior approach through the Douglas space that spares the anterior support structures involved with urinary continence and sexual potency. This approach has been used increasingly in many centers around the world comparing its results with those of the most used standard anterior approach. Several randomized controlled trials, systematic reviews and meta-analyses demonstrated an important advantage relative to standard anterior RARP in terms of early urinary continence recovery, with comparable perioperative and long-term oncological outcomes. Several surgeons are concerned regarding RS-RARP because it appears to increase the risk of positive surgical margins (PSMs). However, this statement is based on low-certainty evidence. Indeed, the available studies compared the results of surgeons who had an initial experience with posterior RARP with those who had a solid experience with anterior RARP. Recent evidence strongly suggests that RS-RARP is feasible and safe not only in low- and intermediate-risk prostate cancer patient but also in challenging scenario such as high-risk setting, salvage prostatectomy and after transurethral resection of the prostate.

Metastatic Castration-Resistant Prostate Cancer: Insights on Current Therapy and Promising Experimental Drugs.

The therapeutic landscape of metastatic hormone sensitive and metastatic castration-resistant prostate cancer (mCRPC) is rapidly changing. We reviewed the current treatment options for mCRPC, with insights on new available therapeutic strategies. Chemotherapy with docetaxel or cabazitaxel (for patients progressing on docetaxel), as well as treatment with androgen receptor axis targeted therapies, and Radium-223 are well-established treatment options for patients with mCRPC. The advent of theragnostic in prostate cancer established Lutetium-177 (177Lu)-PSMA-617 as a new standard of care for PSMA-positive mCRPC previously treated with ARAT and taxane-based chemotherapy. Olaparib, a poly-ADP-ribose polymerase (PARP) inhibitor, is approved for selected patients with mCRPC progressed on ARATs and in combination with abiraterone acetate as first-line treatment for mCRPC. Immunotherapy showed limited efficacy in unselected patients with mCRPC and novel immunotherapy strategies need to be explored. The search for biomarkers is a growing field of interest in mCRPC, and predictive biomarkers are needed to support the choice of treatment and the development of tailored strategies.

Multiparametric Ultrasound Diagnostic Approach to Malignancy-Mimicking Adenomatoid Tumors of the Scrotum: Is Strain Elastography Enough?

Background: Paratesticular tumors (PTs) are very uncommon, accounting for almost 5% of intrascrotal tumors. Of these, adenomatoid tumors (ATs) represent about 30% and most frequently arise in the tail of the epididymis. Ultrasound (US) examination is the first-choice imaging method employed for the evaluation of the scrotum. Unfortunately, there are no specific US-imaging features useful for distinguishing an AT from a malignant lesion. To increase diagnostic accuracy and confidence, new sonographic techniques have incorporated real-time tissue elastography (RTE) under the assumption that malignant lesions are "harder" than benign lesions. Case report: In our paper, we describe a very rare case of a 60-year-old patient with a giant paratesticular mass mimicking malignancy when examined using RTE, i.e., it was stiffer than the surrounding tissue (a hard pattern), which, upon histologic examination, was identified as an AT. Discussion: Our case underscores that there is also a significant overlap between different types of scrotal lesions when RTE is used for examination. Thus, if a PT is found, the imaging approach should always be supplemented with more definitive diagnostic methods, such as FNAC or FNAB, which are the only diagnostic methods capable of leading to a certain diagnosis. Conclusions: Alongside underlining the importance of pre-operative imaging for making correct diagnoses and selecting the correct therapy, we wish to draw our readers' attention to this report in order to demonstrate the clinical implications of a giant AT presenting as stiff lesions when examined using SE.

Predictors of Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

INTRODUCTION: Several programmed death ligand-1 (PD1/L1) immune checkpoint inhibitors (ICIs) are approved in urothelial carcinoma (UC). PATIENTS AND METHODS: To address the need for predictors of the efficacy of ICIs in metastatic urothelial carcinoma (mUC), randomized controlled trials of PD1/L1 inhibitors alone or in combination with chemotherapy in this patient population were systematically reviewed, and differences in ICI-associated survival outcomes according to available baseline variables were quantitatively assessed. RESULTS: The quantitative analysis included 6524 patients with mUC. No visceral metastatic site (HR 0.67; 95% CI, 0.76-0.90) and high PDL-1 expression (HR 0.74; 95% CI, 0.640.87) were significantly associated with a reduced risk of death. CONCLUSION: Treatment with an ICI-containing regimen was associated with a reduced risk of death in mUC patients, which was associated with PDL-1 expression and metastatic site. Further research is warranted.

Artificial intelligence and radiomics in evaluation of kidney lesions: a comprehensive literature review.

Radiomics and artificial intelligence (AI) may increase the differentiation of benign from malignant kidney lesions, differentiation of angiomyolipoma (AML) from renal cell carcinoma (RCC), differentiation of oncocytoma from RCC, differentiation of different subtypes of RCC, to predict Fuhrman grade, to predict gene mutation through molecular biomarkers and to predict treatment response in metastatic RCC undergoing immunotherapy. Neural networks analyze imaging data. Statistical, geometrical, textural features derived are giving quantitative data of contour, internal heterogeneity and gray zone features of lesions. A comprehensive literature review was performed, until July 2022. Studies investigating the diagnostic value of radiomics in differentiation of renal lesions, grade prediction, gene alterations, molecular biomarkers and ongoing clinical trials have been analyzed. The application of AI and radiomics could lead to improved sensitivity, specificity, accuracy in detecting and differentiating between renal lesions. Standardization of scanner protocols will improve preoperative differentiation between benign, low-risk cancers and clinically significant renal cancers and holds the premises to enhance the diagnostic ability of imaging tools to characterize renal lesions.

The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

Radiogenomics in Renal Cancer Management-Current Evidence and Future Prospects.

Renal cancer management is challenging from diagnosis to treatment and follow-up. In cases of small renal masses and cystic lesions the differential diagnosis of benign or malignant tissues has potential pitfalls when imaging or even renal biopsy is applied. The recent artificial intelligence, imaging techniques, and genomics advancements have the ability to help clinicians set the stratification risk, treatment selection, follow-up strategy, and prognosis of the disease. The combination of radiomics features and genomics data has achieved good results but is currently limited by the retrospective design and the small number of patients included in clinical trials. The road ahead for radiogenomics is open to new, well-designed prospective studies, with large cohorts of patients required to validate previously obtained results and enter clinical practice.

Effect of the new 75-mg orodispersible film of sildenafil on erection and sexual quality of life: insights from an observational study.

Background: The newly devised orodispersible film (ODF) of sildenafil is the first phosphodiesterase type 5 inhibitor (PDE5i) available in a 75-mg dose. This intermediate dose and the particular properties of the ODF formulation can improve the clinical management of erectile dysfunction (ED) patients. Aim: We investigated the effects of the sildenafil ODF 75-mg dose on both sexual quality of life and erectile function based on the results from an observational study in daily practice in Italy. Methods: This study was a post hoc analysis of results from an observational, real-life study carried out in ED patients at 6 treatment centers in Italy. All subjects were asked to take the prescribed dose of sildenafil ODF at inclusion (visit 1) and to return for a control visit (visit 2) to confirm or adapt the prescribed dose after a minimum of 4 weeks. An end of study control visit (visit 3) was performed after additional 4 weeks. Outcomes: Erectile function, assessed by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain; sexual quality of life, measured using the sexual quality of life instrument for men (SQoL-M). Results: Among the 36 subjects initially recruited for the 75-mg dose, 5 patients dropped out of the study (2 at visit 2 and 3 at visit 3), none of whom due to treatment inefficacy or serious adverse events. At visit 2, the mean (SD) IIEF-EF scores significantly increased (∆ = 7.97 [4.71], P < 0.0001) as SQoL-M scores also did (∆ = 10.76 [10.46], P < 0.0001). At visit 3, IIEF-EF and SQoL-M scores were still significantly improved compared to baseline (∆ = 10.64 [7.01], P < 0.0001, and ∆ = 18.15 [12.32], P < 0.0001, respectively). By ANCOVA, we found no significant effects for age, BMI, previous use of PDE5i, presence of metabolic comorbidities, or smoking habits on study outcomes at both visits 2 and 3. Clinical implication: The new 75-mg ODF sildenafil formulation is a safe and effective treatment for ED, significantly improving both erectile function and sexual quality of life in patients undergoing treatment. Strengths and limitations: This is the first study assessing the efficacy of the sildenafil ODF 75-mg dose in a real-life setting. However, the small sample size, possible underlying cultural factors, and limited availability of clinically relevant data may have affected the reliability of our results. Conclusion: The use of the 75 mg ODF formulation for sildenafil represents an effective and safe novel treatment option for ED patients.

Efficacy and safety profile of GreenLight laser photoselective vaporization of the prostate in ≥ 75 years old patients: results from the Italian GreenLight Laser Study Group.

BACKGROUND: Benign Prostatic Obstruction (BPO) is the most common non-malignant urological condition among men and its incidence rise with age. Among prostate treatments, GreenLight laser seems to reduce bleeding and would be safer in the aging population. AIMS: We aimed to compare the functional outcomes and safety profile of < 75 years old (Group A) and ≥ 75 years old (Group B) patients. METHODS: In a multicenter setting, we retrospectively analyzed all the patients treated with GreenLight Laser vaporization of the prostate (PVP). RESULTS: 1077 patients were eligible for this study. 757 belonged to Group A (median age 66 years) and 320 to Group B (median age 78 years). No differences were present between the two groups in terms of prostate volume, operative time, hospital stay, PSA decrease over time after surgery, complications and re-intervention rate with a median follow-up period of 18 months (IQR 12-26). Nevertheless, focusing on complications, GreenLight laser PVP demonstrated an excellent safety profile in terms of hospital stay, re-intervention and complications, with an overall 29.6% complication rate in older patients and only two cases of Clavien III. Functional outcomes were similar at 12 month and became in favor of Group A over time. These data are satisfactory with a Qmax improvement of 111.7% and an IPSS reduction of 69.5% in older patients. DISCUSSION AND CONCLUSIONS: GreenLight laser photoselective vaporization of the prostate is a safe and efficient procedure for all patients, despite their age, with comparable outcomes and an equal safety profile.

Management of Urinary Incontinence Following Radical Prostatectomy: Challenges and Solutions.

Urinary incontinence is a common and debilitating problem in patients undergoing radical prostatectomy. Current methods developed to treat urinary incontinence include conservative treatments, such as lifestyle education, pelvic muscle floor training, pharmacotherapy, and surgical treatments, such as bulking agents use, artificial urinary sphincter implants, retrourethral transobturator slings, and adjustable male sling system. Pelvic floor muscle exercise is the most common management to improve the strength of striated muscles of the pelvic floor to try to recover the sphincter weakness. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and a-adrenergic drugs have been proposed as medical treatments for urinary incontinence after radical prostatectomy. Development of new surgical techniques, new surgical tools and materials, such as male slings, has provided an improvement of outcomes after UI surgery. Such improvement is still ongoing, and the uptake of new devices might lead to even better outcomes after UI surgery.

Physical Inactivity, Metabolic Syndrome and Prostate Cancer Diagnosis: Development of a Predicting Nomogram.

Insufficient physical activity (PA) may be a shared risk factor for the development of both metabolic syndrome (MetS) and prostate cancer (PCa). To investigate this correlation and to develop a nomogram able to predict tumor diagnosis. Between 2016 and 2018, a consecutive series of men who underwent prostate biopsy at three institutions were prospectively enrolled. PA was self-assessed by patients through the Physical Activity Scale for the Elderly (PASE) questionnaire; MetS was assessed according to Adult Treatment Panel III criteria. A logistic regression analyses was used to identify predictors of PCa diagnosis and high-grade disease (defined as International Society of Uro-Pathology grade >2 tumors). A nomogram was then computed to estimate the risk of tumor diagnosis. A total of 291 patients were enrolled; 17.5% of them (n = 51) presented with MetS. PCa was diagnosed in 110 (38%) patients overall while 51 presented high-grade disease. At multivariable analysis, age (OR 1.04; 95%CI: 1.00−1.08; p = 0.048), prostate volume (PV) (OR 0.98; 95%CI: 0.79−0.99; p = 0.004), suspicious digital rectal examination (OR 2.35; 95%CI: 1.11−4.98; p = 0.02), total PSA value (OR 1.12; 95%CI: 1.05−1.2; p < 0.001), and PASE score (OR 0.99; 95%CI: 0.98−0.99; p = 0.01) were independent predictors of tumor diagnosis. The latter two also predicted high-grade PCa. MetS was not associated with PCa diagnosis and aggressiveness. The novel nomogram displayed fair discrimination for PCa diagnosis (AUC = 0.76), adequate calibration (p > 0.05) and provided a net benefit in the range of probabilities between 20% and 90%. reduced PA was associated with an increased risk of PCa diagnosis and high-grade disease. Our nomogram could improve the selection of patients scheduled for prostate biopsy at increased risk of PCa.

Accuracy of the European Association of Urology (EAU) NMIBC 2021 scoring model in predicting progression in a large cohort of HG T1 NMIBC patients treated with BCG.

BACKGROUND: Recently, the European Association of Urology Guidelines Panel updated the prognostic factor risk groups model for non-muscle-invasive bladder cancer (NMIBC) with the introduction of a new group of patients at very high risk (VHR). Furthermore, three additional clinical risk factors (i.e., age>70 years, multiple papillary tumors; tumor diameter >3 cm) were proposed. However, the new scoring model was created by analyzing data from patients who did not receive BCG intravesical therapy. METHODS: This is a retrospective multicenter study analyzing data of 920 patients with HGT1 NMIBC that underwent ReTUR e following BCG intravesical therapy. Patients were stratified into risk groups according to the 2021 new EAU NMIBC prognostic factor risk groups model. This study aimed to identify variables related to disease progression in a large cohort of HGT1 NMIBC patients who underwent both Re-TURB and BCG intravesical immunotherapy. RESULTS: Median follow-up was 51 months (IQR 41-75), according to EAU NMIBC 2021 scoring model 179 (19.5%) patients were at VHR. Progression-free survival at 5 years was 68.2% and 59.9% for the whole sample and the VHR group, respectively. At multivariable regression model size >3 cm, multifocal tumor, concomitant CIS and LVI were identified as independently associated with disease progression. CONCLUSIONS: Although patients at VHR are more likely to experience disease progression during follow-up, the European Association of Urology (EAU) NMIBC 2021 scoring model appears to be suboptimal in patients who underwent ReTUR and intravesical BCG therapy.

Effects of Curcumin and Lactoferrin to Inhibit the Growth and Migration of Prostatic Cancer Cells.

Prostate cancer remains one of the main causes of death for men worldwide. Despite recent advances in cancer treatment, patients develop resistance after an initial period of optimal efficacy. Nowadays, it is accepted that natural compounds can result in health benefits with a preventive or adjuvant effect. The purpose of this study was to evaluate the effects of curcumin (CU), a bioactive compound in the spice turmeric, and lactoferrin (LF), a natural glycoprotein with immunomodulatory properties, on DU145 and PC3. Prostate cancer cells were cultured with and without LF (175 µM) and CU (2.5 µg/mL and 5 µg/mL), alone and in combination. Cell viability, migration ability, death receptors (DRs), and integrins (α3, ß1) gene expression were evaluated, as well as human annexin V quantification and Akt phosphorylation. Differences among cells group, defined according to the treatment used, were assessed with ANOVA. The results showed that the effects of CU and LF are different between the two prostatic cell lines analyzed. In DU145, a reduction in cell proliferation and migration is reported both in the presence of single and combined treatments. In PC3 cells, there is a significant reduction in proliferation in the presence of CU alone, while the inhibition of migration is mainly related to the LF treatment and its combination with CU, compared to untreated cells. Moreover, the reduction in gene expression of integrins and Akt pathway activation were observed mostly in the presence of the CU and LF combination, including the upregulation of DR and annexin V levels, with greater significance for the DU145 cells. In conclusion, our results suggest that CU and LF may have a potentially beneficial effect, mainly when administered in combination, leading to a reduction in cancer cells' aggressiveness.

Hot topics in renal cancer pathology: implications for clinical management.

INTRODUCTION: The updated European Association of Urology (EAU) Guidelines issued a weak recommendation for adjuvant pembrolizumab for patients with high-risk operable clear cell Renal Cell Carcinoma (ccRCC). High risk of recurrence was defined, as per protocol-criteria, as T2 with nuclear grade 4 or sarcomatoid differentiation, T3 or higher, regional lymph node metastasis, or stage M1 with no evidence of disease. Considering the heterogeneous population included in the recommendation, it has been questioned if adjuvant pembrolizumab may lead to overtreatment of some patients as well as undertreatment of patients with worse prognosis. AREAS COVERED: In this review, we discuss the issues related to the assessment of pathological features required to identify those patients harboring a high-risk tumor, highlighting the issue related to interobserver variability and discuss the currently available prognostic scoring systems in ccRCC. EXPERT OPINION: PPathologist assessment of prognostic features suffers from interobserver variability which may depend on gross sampling and the pathologist's expertise. The presence of clear cell feature is not sufficient criteria by itself to define ccRCC since clear cell can be also found in other histotypes. Application of molecular biomarkers may be useful tools in the near future to help clinicians identify patients harboring tumors with worse prognosis.