Glycosaminoglycan Replacement Therapy with Intravesical Instillations of Combined Hyaluronic Acid and Chondroitin Sulfate in Patients with Recurrent Cystitis, Post-radiation Cystitis and Bladder Pain Syndrome: A Narrative Review.

Defects in the glycosaminoglycan layer (GAG) of the bladder mucosa have been identified as a significant contributor to the pathogenesis and clinical progression of chronic inflammatory diseases of the bladder, such as post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections. This narrative review aims to explore the contemporary evidence on the role of GAG reconstitution with intravesical installations of hyaluronic acid and chondroitin sulfate in the management of those patients, with a goal to provide valuable insights for clinical practice. The reviewed studies consistently demonstrate that GAG reconstitution can result in varying degrees of clinical improvement in patients with post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections, and is associated with a very favorable safety profile. While the available evidence is growing, its level is still limited, mainly by relatively low number of randomized controlled trials, with small sample sizes. Further research with larger, well-designed trials is needed to solidify the findings and optimize the clinical application of GAG reconstitution.

Comparison of Multiparametric MRI, [68Ga]Ga-PSMA-11 PET-CT, and Clinical Nomograms for Primary T and N Staging of Intermediate-to-High-Risk Prostate Cancer.

PURPOSE OF THE REPORT: Although multiparametric magnetic resonance imaging (mpMRI) is commonly used for the primary staging of prostate cancer, it may miss non-enlarged metastatic lymph nodes. Positron emission tomography-computed tomography targeting the prostate-specific membrane antigen (PSMA PET-CT) is a promising method to detect non-enlarged metastatic lymph nodes, but more data are needed. MATERIALS AND METHODS: In this single-center, prospective study, we enrolled patients with intermediate-to-high-risk prostate cancer scheduled for radical prostatectomy with pelvic node dissection. Before surgery, prostate imaging with mpMRI and PSMA PET-CT was used to assess lymph node involvement (LNI), extra-prostatic extension (EPE), and seminal vesicle involvement (SVI). Additionally, we used clinical nomograms to estimate the risk of these three outcomes. RESULTS: Of the 74 patients included, 61 (82%) had high-risk prostate cancer, and the rest had intermediate-risk cancer. Histopathology revealed LNI in 20 (27%) patients, SVI in 26 (35%), and EPE in 52 (70%). PSMA PET-CT performed better than mpMRI at detecting LNI (area under the curve (AUC, 95% confidence interval): 0.779 (0.665-0.893) vs. 0.655 (0.529-0.780)), but mpMRI was better at detecting SVI (AUC: 0.775 (0.672-0.878) vs. 0.585 (0.473-0.698)). The MSKCC nomogram performed well at detecting both LNI (AUC: 0.799 (0.680-0.918)) and SVI (0.772 (0.659-0.885)). However, when the nomogram was used to derive binary diagnoses, decision curve analyses showed that the MSKCC nomogram provided less net benefit than mpMRI and PSMA PET-CT for detecting SVI and LNI, respectively. CONCLUSIONS: mpMRI and [68Ga]Ga-PSMA-11 PET-CT are complementary techniques to be used in conjunction for the primary T and N staging of prostate cancer.

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.

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.

A systematic review evaluating the effectiveness of exercise training on physical condition in prostate cancer patients undergoing androgen deprivation therapy.

Background: Androgen deprivation therapy (ADT) is an effective prostate cancer (PCa) treatment strategy that can curb the development or progression of the disease. This review aimed to examine and summarize available systematic reviews/meta-analyses (SRs/MAs) of exercise training on physical condition of PCa patients undergoing ADT. Methods: A comprehensive search of 8 databases was conducted for relevant literature published before April 25, 2022 with the language restrictions of Chinese and English. Two reviewers independently assessed the methodological quality, risk of bias, reporting quality, and evidence quality of the included SRs/MAs using a range of evaluation tools, including A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Grades of Recommendations, Assessment, Development and Evaluation (GRADE). Results: This review included 8 SRs/MAs which included a total of 94 studies. Ultimately, A total of 51 outcomes was included, regarding 11 different outcome categories. The AMSTAR-2 tool showed that 3 SRs/MAs had moderate methodological quality, 4 SRs/MAs had very low quality, and the remaining 1 had low quality. According to the ROBIS scale, 3 SRs/MAs had a high risk of bias. The PRISMA checklist showed that the primary reporting faults were protocol registration and funding source. The GRADE system was used to analyze the evidence quality of the 51 outcomes, and no high-quality evidence was found. However, moderate-quality evidence indicated that exercise training may improve body composition [by lowering body fat mass (BFM) and body fat rate (BFR)], muscular strength, and quality of life (QoL) in PCa patients undergoing ADT. Low-quality evidence demonstrated that exercise training could improve such symptoms as fatigue, depression, sexual function, and cardiometabolic changes. Conclusions: Available evidence suggests that exercise training may be used as an adjuvant treatment for PCa patients undergoing ADT to improve several aspects of general health. Studies with more rigorous designs and larger sample sizes are needed to support our findings with more robust evidence.

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.

Mixed epithelial and stromal tumor of the kidney: A case report.

Mixed epithelial and stromal tumor (MEST) is a rare neoplasm of the kidney, affecting mostly women at menopausal age. While few cases of malignant transformation have been described in the literature, MEST is usually considered a benign tumor with minimal risk of local recurrence or distance metastases. The current study presents a case of a 18-year old male patient with a cystic tumor of the left kidney incidentally diagnosed on magnetic resonance imaging of the heart performed for other reasons. The patient underwent a partial nephrectomy, with perioperative course being uneventful. The pathology report revealed MEST of the kidney. No local recurrence nor disease progression have been observed in the patient during the one-year follow-up period. The present case report is evidence that may help in developing guidelines on the management of patients with benign renal masses.

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.

Diagnostic Performance of Preoperative Choline-PET/CT in Patients Undergoing Salvage Lymph Node Dissection for Recurrent Prostate Cancer: A Multicenter Experience.

We aimed to retrospectively analyze consecutive prostate cancer patients diagnosed with biochemical or clinical recurrence after local treatment with curative intent, with no evidence of distant metastases, who underwent positron emission tomography/computed tomography (PET/CT) with choline followed by salvage lymph node dissection (SLND) in three academic centers between 2013 and 2020. A total of 27 men were included in the analyses. Sensitivity, specificity, positive and negative predictive values, and accuracy of choline-PET/CT in predicting pathology-proven lymph node involvement were 75%, 43%, 79%, 38% and 67% on per-patient and 70%, 86%, 80%, 78%, and 79% on per-site analyses, respectively, with the differences in specificity and NPV between per-patient and per-site analyses being statistically significant (p = 0.03 and 0.04, respectively). The study provides further insight into the role of preoperative choline-PET/CT in patients undergoing SLND for recurrent PC.

High-Intensity Focused-Ultrasound Focal Therapy Versus Laparoscopic Radical Prostatectomy: A Comparison of Oncological and Functional Outcomes in Low- and Intermediate-Risk Prostate Cancer Patients.

To compare oncological and functional outcomes of high-intensity focused-ultrasound (HIFU) focal therapy (FT) versus laparoscopic radical prostatectomy (LRP) in patients treated for low- or intermediate-risk prostate cancer (PCa), we retrospectively analyzed data of consecutive patients comprising 30 men, who underwent HIFU-FT, and 96 men who underwent LRP, in an academic center. Oncological outcomes were assessed based on the follow-up prostate-specific antigen values. We used the International Index of Erectile Function short form score to assess erectile function (EF). Urinary continence status was defined based on the number of pads used per day. Median follow-up was 12.5 and 19.1 months in the LRP and HIFU-FT groups, respectively. The effects were computed after propensity score matching and expressed as average treatment effect (ATE). Compared to LRP, HIFU-FT was associated with increased risk of treatment failure (ATE 0.103-0.164, depending on definition, p < 0.01) and lower risk of urinary incontinence (ATE -0.808 at 12 months, p < 0.01). Risk of erectile dysfunction was higher in the LRP group (ATE 5.092, p < 0.01). Our results demonstrate that HIFU-FT may be a reasonable treatment option in selected PCa patients, willing to preserve their EF and urinary continence yet accepting a higher risk of treatment failure.

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.

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.

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.

Uro-oncology in the era of social distancing: the principles of patient-centered online consultations during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic poses significant challenges to healthcare facilities and as per social distancing measures, many consultations are now being carried out via means of telemedicine. As some urologists may not be skilled with remote consultations, there is a need for recommendations on patient-centered online medical counseling. MATERIAL AND METHODS: We have identified eight areas of excellence and defined the principles based on our experience. RESULTS: A professional setting should be provided, in which the privacy of the patient can be ensured. Accompanying persons should be encouraged into the consultation. Proper introduction could serve not only to verify the personality of the patient, but also to provide them with a sense of confidentiality. The interview should be held in a way to overcome the limitations of non-physical encounters, and pande-mic-specific issues should be taken into consideration. When arranging plans, the physician should judge accordingly in regards to what type of management is inevitable or safe, as well as available at this point; strict follow-up should be arranged. As home isolation may lead to unfavorable changes in lifestyle, this issue should be addressed too. The patient should be guided on how to self-educate. Concluding the visit should be aimed at proper evaluation of the patient's comprehension of the consultation. CONCLUSIONS: It is vital to pursue consistency in providing care to patients. While online counseling may seem challenging, if one adheres to the principles of patient-centered practice, telemedicine may become a valuable tool in maintaining the best-quality care amid the ongoing pandemic.

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.