The role of VI-RADS scoring criteria for predicting oncological outcomes in bladder cancer.

PURPOSE: Our purpose was to evaluate the prognostic value of Vesical Imaging Reporting and Data System (VI-RADS) in bladder cancer (BCa) staging and predicting recurrence or progression. METHODS: We retrospectively analyzed the prospectively collected data from 96 patients with bladder tumors who underwent VI-RADS-based multiparametric magnetic resonance imaging (mpMRI) before endourological treatment from April 2021 to December 2022. Diagnostic performance was evaluated by comparing mpMRI reports with final pathology, using logistic regression for muscle-invasive bladder cancer (MIBC) predictors. Follow-up until May 2023 included Kaplan-Meier and Cox regression analysis to assess VI-RADS predictive roles for recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: A total of 96 patients (19.8% women, 80.2% men; median age 68.0 years) were included, with 71% having primary tumors and 29% recurrent BCa. Multiparametric MRI exhibited high sensitivity (92%) and specificity (79%) in predicting MIBC, showing no significant differences between primary and recurrent cancers (AUC: 0.96 vs. 0.92, P = .565). VI-RADS emerged as a key predictor for MIBC in both univariate (OR: 40.3, P < .001) and multivariate (OR: 54.6, P < .001) analyses. Primary tumors with VI-RADS ≥ 3 demonstrated significantly shorter RFS (P = .02) and PFS (P = .04). CONCLUSIONS: In conclusion, mpMRI with VI-RADS has a high diagnostic value in predicting MIBC in both primary and recurrent BCa. A VI-RADS threshold ≥ 3 is a strong predictor for MIBC, and in primary tumors predicts early recurrence and progression.

Pro-Inflammatory Cytokine Gene Expression in Penile Cancer: Preliminary Studies.

Background and Objectives: Penile cancer is a rare neoplasm in developed countries with an incidence of 0.8/100,000 per male inhabitant. Despite the development of personalized medicine and multimodal treatment, the outcome of penile cancer treatment is insufficient. Our study aimed to assess the levels of pro-inflammatory cytokines' mRNA such as interleukin 1-A (encoded by IL1A gene, alias IL-1A), interleukin 1-B (IL1B, IL-1B), interleukin 1 receptor antagonist (IL1RN, IL-1RN), interleukin 6 (IL6, IL-6), transforming growth factor ß1 (TGFB1, TGFß-1), and Interferon-gamma (INFG, INF-γ) in penile cancer tissue and associate them with tumor progression and patient survival. Material and Methods: Skin biopsies from patients suffering from penile cancer (n = 6) and unchanged foreskin from 13 healthy adult males undergoing circumcision due to a short frenulum were obtained. Pro-inflammatory cytokine mRNA levels were quantified through qPCR. Results: We observed higher expression of pro-inflammatory cytokine genes (IL-1A, IL-1B, IL-6, INF-γ, TGF-ß) in penile cancer tissue. The average follow-up period was 48 months (range: 38-54 months), during which only one penile tumor progression was observed However, this was without association with the nature of tumor (patient refused radical treatment). Conclusions: This is the first study to show increased expression of cytokines such as IL-1A, IL-1B, IL-6, INF-γ, and TGF-ß in penile cancer with positive correlation between TNM staging and INF-γ levels in tumor samples (rs = 0.672, p = 0.045), which may be associated with the immunosuppressive role of the tumor environment.

The Clinical Features of Incidentally Diagnosed Urothelial Bladder Cancer: A Retrospective Data Analysis.

INTRODUCTION: The aim of this study was to evaluate the prevalence and clinical features of incidental bladder cancer (BC) diagnosis, with special emphasis on possible associations between incidental diagnosis and primary disease stage or grade. METHODS: We retrospectively included 501 consecutive patients who underwent transurethral resection of bladder tumor and were diagnosed with primary urothelial carcinoma of the bladder between January 2013 and February 2021 in a university hospital. The type of diagnosis (incidental or nonincidental), patient baseline characteristics and primary stage and grade were studied for interdependencies. RESULTS: 28.5% of all patients and 19.8% of high grade (HG) BC patients had been diagnosed incidentally, most commonly with ultrasound. Incidental diagnosis was associated with lower primary stage and grade of the disease. Most importantly, on multivariable analysis, which included baseline patient characteristics and type of diagnosis, in the subgroup of HG BC patients, muscle-invasive BC (MIBC) or metastatic disease was three times less likely to be diagnosed incidentally than non-MIBC (odds ratio: 0.31, 95% confidence interval: 0.14-0.71, p = 0.006). CONCLUSIONS: The study is first to demonstrate that incidental diagnosis of HG BC may be surprisingly prevalent and associated with lower rates of muscle invasion or metastatic disease.

Assessment of selected quality of life domains in patients who have undergone conservative or radical surgical treatment for penile cancer: an observational study.

Background Surgery is the standard treatment for organ-restricted penile cancer, but it is also a disfiguring procedure that can profoundly affect quality of life. Using a survey, in this study we assessed the effect of different surgical invasiveness on satisfaction in selected life domains of patients who underwent penile-sparing surgery and partial penectomy. METHODS: Forty patients who underwent penile-sparing surgery (n=13) or partial penectomy (n=27) were enrolled in the study. The response rate was 71%. Information was obtained after surgery on sexuality, self-esteem, masculinity and partner relationships using the International Index of Erectile Function, the Self-Esteem Scale and the Conformity to Masculinity Norms Inventory questionnaires. We evaluated the effect of primary surgery type on selected domains of quality of life and correlations between study variables after surgery. RESULTS: High self-esteem, satisfactory erectile function and masculinity results in both groups were comparable to those in the published literature. Men who underwent less disfiguring treatment had a significantly higher sense of masculinity than those who underwent partial penectomy (P=0.05). No significant differences were observed in erectile dysfunction and self-esteem. The level of aggressiveness of a surgical procedure was a predictor of sense of masculinity (P=0.01), but was not associated with self-esteem and sexual dysfunction (P=0.28 and P=0.55 respectively); 83% of patients were able to satisfactorily maintain partner relationships. CONCLUSIONS: Disfiguring treatments for penile cancer significantly interfere with the sense of masculinity, but sexual functioning and self-esteem do not differ according to the type of surgical procedure. Most men maintained stable partner relationships after surgery, regardless of surgery type.

International phase IV validation study of an EORTC quality of life questionnaire for testicular cancer patients: the EORTC QLQ-TC26.

BACKGROUND: Given the high cure-rate for testicular cancer (TC) and the patients' young age, comprehensive evaluation of health-related quality of life (HRQOL) is an important consideration in this patient population. The EORTC QLQ-TC26 questionnaire module has been developed to supplement the EORTC QLQ-C30 in assessing TC-specific HRQOL in clinical trials and routine clinical practice. This international, multicentre phase IV validation study evaluated the psychometric properties of the new module. METHODS: This international, multicentre phase IV validation study enrolled testicular cancer patients from seven European countries. Patients completed the EORTC quality of life core questionnaire EORTC QLQ-C30 and the QLQ-TC26 at two consecutive time points and a debriefing questionnaire regarding the QLQ-TC26 after baseline assessment. Psychometric evaluation included examination of the hypothesized module scale structure, internal consistency and test-retest reliability, known-groups validity, responsiveness to change over time and cross-cultural acceptability. RESULTS: Data from 313 patients (mean age 38.6, SD 9.5) were analysed. All items exhibited a high completion rate with less than 2.4% missing values except for the sexuality items (up to 8.8%). The confirmatory factor analysis supported the hypothesised scale structure of the QLQ-TC26. Test-retest reliability was good for 8 of 12 scales (intraclass correlation: R t1|t2 ranged from 0.71-0.91) and four scales did not meet the acceptable criteria. Internal consistency was good for all twelve scales (Cronbach alpha = 0.79-0.90), except Communication (alpha = 0.67) and Sexual Functioning (alpha = 0.62). The module was able to distinguish clearly between patients with differing clinical status. Responsiveness to change over time was acceptable. CONCLUSION: The EORTC QLQ-TC26 is a valid, reliable and well-accepted condition-specific questionnaire, supplementing the EORTC QLQ-C30, for the assessment of testicular cancer patients' HRQOL in clinical trials.

Adjuvant chemotherapy after radical nephroureterectomy does not improve survival in patients with upper tract urothelial carcinoma: a joint study by the European Association of Urology-Young Academic Urologists and the Upper Tract Urothelial Carcinoma Collaboration.

OBJECTIVE: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events. RESULTS: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10% after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95% confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95% CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies. CONCLUSION: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required.

The diagnosis of benign prostatic obstruction: Development of a clinical nomogram.

AIMS: To develop a nomogram predicting benign prostatic obstruction (BPO). METHODS: We included in this study 600 men with lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) who underwent standardized pressure flow studies (PFS) between 1996 and 2000. Complete clinical and urodynamic data were available for all patients. Variables assessed in univariate and multivariate logistic regression models consisted of IPSS, PSA, prostate size, maximal urinary flow rate (Qmax) at free flow, residual urine (RU), and bladder wall thickness (BWT). These were used to predict significant BPO (defined as a Schäfer grade ≥ 3 in PFS). RESULTS: A preliminary multivariate model, including IPSS, Qmax at free flow and RU, suggested that only Qmax at free flow was a statistically significant predictor of BPO (P = 0.00) with a predictive accuracy (PA) of 82%. Further development of the multivariate model showed how the inclusion of BWT did not increase PA. Only transitional zone volume (TZV) proved to be an additional statistically significant predictor for BPO (P = 0.00). The combination of Qmax at free flow and TZV demonstrated a PA of 83.2% and were included in the final nomogram format. CONCLUSIONS: We developed a clinical nomogram, which is both accurate and well calibrated, which can be helpful in the management of patients with LUTS and BPE. External validation is warranted to confirm our findings.

Epidemiology of penile cancer in Poland compared to other European countries.

OBJECTIVES: To examine the epidemiology of penile cancer in Poland compared to other European countries. MATERIALS AND METHODS: Incidence and mortality data were acquired from the national cancer registries in Europe and WHO Mortality Database, respectively. The data are presented as age-standardised morbidity and mortality rates, calculated according to the standard population of the world. We utilised Joinpoint analysis to assess the trends in morbidity and mortality and calculated the average rate of increase or decrease (Annual Percentage Change, Average Annual Percentage Change). Additionally, we estimate the proxy survival rates for each country. RESULTS: Our study is the first to cover the incidence of penile cancer in many European countries and estimates an approximate survival rate for large populations, which is rarely cited in the literature. The 40+ age group presented graphically in the article covered more than 90% of penile cancer cases and deaths. In the countries examined, there was an excess of deaths over incidence in the oldest age groups (75 years or older). Poland had intermediate incidence and mortality rates. CONCLUSIONS: Unlike many European countries, Poland is witnessing an increasing trend of penile cancer mortality. The higher death toll among those aged 75 years or older may suggest a lack of recognition of cancer symptoms and inadequate attention to elderly patients by the healthcare system. There is also evidence of underreporting penile cancer cases. Establishing centralised healthcare systems for rare cancers is a commendable development that should be emulated by other European countries, including Poland.

European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer.

BACKGROUND: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications. OBJECTIVE: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa. DESIGN, SETTING, AND PARTICIPANTS: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores. RESULTS AND LIMITATIONS: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy. CONCLUSIONS: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community. PATIENT SUMMARY: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.

Incidental Diagnosis of Urothelial Bladder Cancer: Associations with Overall Survival.

BACKGROUND: We investigated whether an incidental diagnosis (ID) of bladder cancer (BC) was associated with improved survival. METHODS: We retrospectively reviewed data of consecutive patients with no prior diagnosis of urothelial cancer who underwent a primary transurethral resection of bladder tumor (pTURBT) between January 2013 and February 2021 and were subsequently diagnosed with urothelial BC. The type of diagnosis (incidental or non-incidental) was identified. Overall, relative, recurrence-free, and progression-free survival rates (OS, RS, RFS, and PFS) after pTURBT were evaluated using the Kaplan-Meier curves and long-rank tests. A multivariable Cox regression model for the overall mortality was developed. RESULTS: A total of 435 patients were enrolled. The median follow-up was 2.7 years. ID cases were more likely to be low-grade (LG) and non-muscle-invasive. ID vs. non-ID was associated with a trend toward an improved 7-year OS (66% vs. 49%, p = 0.092) and a significantly improved 7-year OS, if incidental cases were limited to ultrasound-detected tumors (75% vs. 49%, p = 0.013). ID was associated with improved survival among muscle-invasive BC (MIBC) patients (3-year RS: 97% vs. 23%, p < 0.001), but not among other subgroups stratified according to disease stage or grade. In multivariable analysis, only age, MIBC, and high-grade (HG) cancer demonstrated an association with mortality. PFS and RFS among non-MIBC patients did not differ in regard to the type of diagnosis. CONCLUSIONS: Incidental diagnosis may contribute to an improved survival in BC patients, most probably in the mechanism of the relative downgrading of the disease, including the possible overdiagnosis of LG tumors. Nevertheless, in the subgroup analyses, we noted marked survival benefits in MIBC cases. Further prospective studies are warranted to gain a deeper understanding of the observed associations.

Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future.

Patient-reported pain associated with grid-based transperineal magnetic resonance imaging (MRI)/ultrasound (US) software fusion biopsy of the prostate under local anesthesia: a multicenter experience.

Background: Biopsy by transperineal (TP) approach is recommended standard for prostate cancer (PC) diagnosis. To avoid pain, patients undergoing TP biopsy may be offered sedation or general anesthesia. Our aim was to investigate the degree of patient-reported pain for magnetic resonance imaging (MRI)/ultrasound (US) fusion biopsy of the prostate being performed under local anesthesia (LA) and to study for possible factors associated with increased risk of significant pain (SP) in this setting. Methods: In this retrospective observational study, we reviewed data of consecutive patients without a prior diagnosis of PC who underwent MRI/US software fusion biopsy of the prostate under LA with lidocaine at two centers between May 2020 and April 2022, and who reported their periprocedural pain on a Wong-Baker FACES Pain Rating Scale (0-10). We defined SP as reported pain score of 6-10. Patient and procedure characteristics together with SP were studied for interdependencies. Results: A total of 299 patients were included. Median pain score was 2 (interquartile range: 2-4), with SP having been reported by 55 (18.4%) patients. Among patient characteristics, only age demonstrated association with SP [odds ratio (OR), per 10 years =0.53, 95% confidence interval (CI): 0.35-0.80, P=0.003] and patients aged 62 or above were significantly less likely to report SP (OR =0.33, 95% CI: 0.18-0.60, P<0.001). Conclusions: Performing TP MRI/US fusion prostate biopsy under LA is associated with low rates of SP, with the risk being significantly lower in older men. The results of this study can serve as evidence resource for preprocedural counselling in patients especially concerned about the risk of pain.

Quantification of Gleason Pattern 4 at MRI-Guided Biopsy to Predict Adverse Pathology at Radical Prostatectomy in Intermediate-Risk Prostate Cancer Patients.

BACKGROUND: Data on Gleason pattern 4 (GP4) amount in biopsy tissue is important for prostate cancer (PC) risk assessment. We aim to investigate which GP4 quantification method predicts adverse pathology (AP) at radical prostatectomy (RP) the best in men diagnosed with intermediate-risk (IR) PC at magnetic resonance imaging (MRI)-guided biopsy. METHODS: We retrospectively included 123 patients diagnosed with IR PC (prostate-specific antigen <20 ng/mL, grade group (GG) 2 or 3, no iT3 on MRI) at MRI-guided biopsy, who underwent RP. Twelve GP4 amount-related parameters were developed, based on GP4 quantification method (absolute, relative to core, or cancer length) and site (overall, targeted, systematic biopsy, or worst specimen). Additionally, we calculated PV×GP4 (prostate volume × GP4 relative to core length in overall biopsy), aiming to represent the total GP4 volume in the prostate. The associations of GP4 with AP (GG ≥ 4, ≥pT3a, or pN1) were investigated. RESULTS: AP was reported in 39 (31.7%) of patients. GP4 relative to cancer length was not associated with AP. Of the 12 parameters, the highest ROC AUC value was seen for GP4 relative to core length in overall biopsy (0.65). an even higher AUC value was noted for PV × GP4 (0.67), with a negative predictive value of 82.8% at the optimal threshold. CONCLUSIONS: The lack of an association of GP4 relative to cancer length with AP, contrasted with the better performance of other parameters, indicates directions for future research on PC risk stratification to accurately identify patients who may not require immediate treatment. Incorporating formulas aimed at GP4 volume assessment may lead to obtaining models with the best discrimination ability.

Predictors of Clinically Significant Prostate Cancer in Patients with PIRADS Categories 3-5 Undergoing Magnetic Resonance Imaging-Ultrasound Fusion Biopsy of the Prostate.

Prostate biopsy is recommended in cases of positive magnetic resonance imaging (MRI), defined as Prostate Imaging Reporting and Data System (PIRADS) category ≥ 3. However, most men with positive MRIs will not be diagnosed with clinically significant prostate cancer (csPC). Our goal was to evaluate pre-biopsy characteristics that influence the probability of a csPC diagnosis in these patients. We retrospectively analyzed 740 consecutive men with a positive MRI and no prior PC diagnosis who underwent MRI-ultrasound fusion biopsies of the prostate in three centers. csPC detection rates (CDRs) for each PIRADS category were calculated. Patient, disease, and lesion characteristics were studied for interdependencies with the csPC diagnosis. The CDR in patients with PIRADS categories 3, 4, and 5 was 10.5%, 30.7%, and 54.6%, respectively. On both uni- and multivariable regression models, older age, being biopsy-naïve, prostate specific antigen ≥ 10 ng/mL, smaller prostate volume, PIRADS > 3, a larger maximum lesion size, a lesion in the peripheral zone, and a positive digital rectal examination were associated with csPC. In this large, multicenter study, we provide new data regarding CDRs in particular PIRADS categories. In addition, we present several strong predictors that further alter the risk of csPC in MRI-positive patients. Our results could help in refining individual risk assessment, especially in PIRADS 3 patients, in whom the risk of csPC is substantially low.

The Impact of the Ongoing COVID-19 Epidemic on the Increasing Risk of Adverse Pathology in Prostate Cancer Patients Undergoing Radical Prostatectomy.

We aimed to assess whether the ongoing course of the COVID-19 epidemic has been associated with an increased risk of adverse pathology (AP) findings in prostate cancer (PC) patients treated with radical prostatectomy (RP). We performed a retrospective data analysis which included 408 consecutive, non-metastatic, previously untreated PC patients who underwent RP in our institution between March 2020 and September 2021. Patients were divided into two equally numbered groups in regard to the median surgery date (Early Epidemic [EE] and Late Epidemic [LE]) and compared. Adverse pathology was defined as either grade group (GG) ≥ 4, pT ≥ 3a or pN+ at RP. Patients in the LE group demonstrated significantly higher rates of AP than in the EE group (61 vs. 43% overall and 50 vs. 27% in preoperative non-high-risk subgroup, both p < 0.001), mainly due to higher rates of upgrading. On multivariable analysis, consecutive epidemic week (odds ratio: 1.02, 95% confidence interval: 1.00−1.03, p = 0.009) as well as biopsy GG ≥ 2 and a larger prostate volume (mL) were associated with AP in non-high-risk patients. The study serves as a warning call for increased awareness of risk underassessment in contemporarily treated PC patients.

Carcinogenic biomarkers of exposure in the urine of heated tobacco product users associated with bladder cancer: A systematic review.

To identify biomarkers of exposure present in Heated Tobacco Products (HTPs) users' urine which are associated with bladder cancer and to compare quantitative biomarker levels to those seen in combustible cigarette users. A systematic literature review was conducted in December 2020 with no date limits. Relevant studies that reported quantitative urinary biomarker of exposure in HTP users were included. Biomarkers and their parent compounds were classified by carcinogenicity according to the International Agency for Research on Cancer Monographs and were cross-referenced with the Collaborative on Health and the Environment Toxicant and Disease Database to determine associations with bladder cancer. Our literature search identified 561 articles and 30 clinical trial reports. 11 studies met inclusion criteria. These studies identified 29 biomarkers of exposure present in HTP users' urine, which reflect exposure to 21 unique parent compounds. Of these parent compounds, 14 are carcinogens and 10 have a known link to bladder cancer. HTP users' biomarkers of exposure were present at lower levels than combustible cigarette users but higher than never-smokers. Biomarkers of exposure to bladder carcinogens are present in the urine of HTP users. While levels of these biomarkers appear to be lower than combustible cigarette users, chronic urothelial exposure to bladder carcinogens is concerning and degree of bladder cancer risk remains unknown. Further long-term study is needed to elucidate the bladder cancer risk of HTP use.

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Alternative tobacco products use and its impact on urologic health - will the lesser evil still be evil? A commentary and review of literature.

INTRODUCTION: Alternative tobacco products, including electronic cigarettes (e-cigarettes) and non-combustible tobacco products or heat-not-burn (HNB) products, are substitutes to conventional combustible cigarettes with the potential to impact urologic health, similar to traditional smoking. Most urologists, however, have limited knowledge of these products and are unfamiliar with their potential health implications. We conducted a review to assess the impact of e-cigarettes and HNB products on urologic health. MATERIAL AND METHODS: A bibliographic search covering the period up to April, 2021 was conducted using MEDLINE®/PubMed® and Google Scholar. Articles were reviewed and categorized based on the potential impact on erectile dysfunction, semen quality, lower urinary tract symptoms, genitourinary malignancies, and smoking cessation. Data were extracted, analyzed and summarized. RESULTS: Mature data on the long-term impact of e-cigarette and HNB product use on urologic health are lacking. E-cigarette and HNB vapors appear to contain decreased concentrations of chemicals responsible for erectile dysfunction compared to tobacco smoke but may play a role through endothelial damage. Use of e-cigarettes is associated with lower sperm counts. No definitive data has shown a link between e-cigarette or HNB product use and lower urinary tract symptoms. Multiple carcinogens including those specifically linked to bladder cancer have been identified in the urine of e-cigarette and HNB product users. Limited data suggest e-cigarettes may aid in smoking cessation. CONCLUSIONS: Urologists may benefit from understanding the urologic health concerns surrounding e-cigarettes and HNB product use and patients may benefit from being properly educated.

Laparoscopic radical prostatectomy and extended pelvic lymph node dissection: a combined technique.

INTRODUCTION: The important part of radical prostatectomy (RP) for high risk (HR) is extended pelvic lymph node dissection (ePLND). This method consists of two stages of surgery usually performed at the compartment (pre- or transperineally). AIM: We present our new combined technique of RP using two different approaches: a pre-peritoneal approach for laparoscopic radical prostatectomy (LRP) and a transperitoneal approach for ePLND. MATERIAL AND METHODS: This study included 30 patients aged 53 to 75 years (mean age: 64 years) with prostate cancer who underwent LRP and ePLND using a combined technique. After the pre-peritoneal LRP, transposition of the trocars into the peritoneal cavity was performed without changing their location, except the extreme left trocar, which was inserted through a new approach. RESULTS: The total duration of surgery was 155 to 290 min (mean: 215 min); ePLND lasted from 35 to 85 min (mean: 56 min). The movement of trocars into the peritoneal cavity was a very simple maneuver, taking up to 1 min without any complications. The number of removed lymph nodes (LNs) ranged from 13 to 28 (mean: 16.8). A positive margin was found in 5 (16%) patients. We recognized positive nodes in 9 (30%) patients. CONCLUSIONS: The combined technique is both feasible and safe. Performing the most difficult maneuver, removal of the prostate, in the first stage appears to be more comfortable for the operator. The timing of the PLND stage in the combined technique and the number of removed LNs do not differ from the standard lenticular access.

Active surveillance for low-risk prostate cancer - in pursuit of a standardized protocol.

INTRODUCTION: Active surveillance (AS) is a management option recommended by most guidelines for low risk clinically-localized prostate cancer (LR-CLPC). Data shows that AS is being increasingly adopted into clinical practice worldwide. Our aim was to review the up-to date guidelines and observational studies in regards to AS in LR-CLRPC to gain insight into principles of contemporary clinical practice. MATERIAL AND METHODS: Several guidelines on the management of low-risk prostate cancer were reviewed for evidence-based recommendations regarding the protocol of AS. We reviewed the available literature for most recent studies on AS in LR-CLPC. RESULTS: No uniform protocol of AS in LR-CLPC has been recommended up to date and available guidelines significantly differ in terms of protocol schedules and the role of particular tools in monitoring for disease progression. Nevertheless, recent studies on AS in LR-CLPC, in which various protocols were adopted, have demonstrated promising outcomes in regards to cancer-specific survival (99-100% at 5 years, 98.1-99.9% at 10 years, and 94.3-96% at 15 years), with high rates of men remaining within the protocols (23-39% at 10 years). CONCLUSIONS: This article is a call for focusing further research on development and recommending a precise and standardized, evidence-based protocol for AS in LR-CLPC.