BCG and bladder cancer. Forty-eight years after Morales report.

Although BCG use as an anticancer drug was nearly abandoned due to the poor results in most tumors, in 1976 Morales reported a relevant reduction in recurrence with intravesical BCG in few patients affected by NMIBC. Since then BCG was globally accepted as an empirical and effective therapy in treating Tis and preventing recurrence of intermediate and high risk NMIBC. Forty-eight years after Morales' report, although some open questions remain object of debate, we have been able to find answers to many doubts improving BCG activity and toxicity. We better select patients undergoing BCG and many trials have indicated the best dosage and schedule. Moreover, we are able to better identify the patient unresponsive to BCG who might benefit of a timely radical cystectomy. We are also aware of the difficulties and toxicities that can be encountered with BCG use in every-day clinical practice. Research is ongoing to obtain genetically modified BCG to increase its efficacy and reduce toxicity. Moreover, the combination of BCG with other immunotherapeutic drugs given intravesically or systemically, first immune checkpoint inhibitors, is under study to obtain a response in patients unresponsive or intolerant to BCG. Almost 50 years after Morales publication, intravesical BCG remains an inalienable tool against NMIBC.

Can COVID-19 pandemic surveillance reduce nosocomial urinary infections in urologic surgery?

INTRODUCTION: Since COVID-19 pandemic spread, strict preventive measures were adopted to reduce the risk of transmission. Antiseptic dispensers for hand hygiene were diffusely available for patients and hospital staff. To investigate the prophylactic role played by the strict antiseptic rules adopted during pandemic, the rates of nosocomial urinary infections in 2019 and 2020 were compared. MATERIALS AND METHODS: Patients' clinical pre-operative characteristics, symptoms, fever, and laboratory data were recorded pre- and post-operatively. Urological surgery was classified in five categories: 1. major surgery 2. upper urinary tract endoscopy, 3. lower urinary tract endoscopy, 4. minor surgery, and 5. Nephrostomy and ureteral stenting. Clavien-Dindo complication score was used. Statistical analysis was performed with R 3.4.2 software. RESULTS: Out of 495 patients, 383 (57.1%) underwent surgical intervention in pre-pandemic March-May 2019 period and 212 (42.9%) in the same pandemic 2020 interval. Preoperatively, 40 (14.1%) and 11 (5.2%) and 77 (27.3%) and 37 (17.5%) patients had fever (p < 0.003) and leukocytosis (p < 0.02), in 2019 and 2020 respectively. Urine culture was positive in 29 (10.2%) and 13 (6.2%) patients respectively (p = 0.22). Post-operatively, 54 (19.1%) and 22 (10.4%) patients and 17 (6.1%) and 2 (0.6%) patients showed fever (p < 0.003) and positive urineculture (p < 0.03), in 2019 and 2020 respectively. DISCUSSION AND CONCLUSION: Preoperative and post-operative clinical and laboratory signs of nosocomial urinary infection showed a statistically significant lower incidence during the pandemic period in 2020. This observation could be ascribed to the strong preventive measures, to the medical staff high adherence to hygiene and the diffuse availability of hand sanitizers.

A Prospective Observational Study on the Structuring Process and Implementation of a Large Regional, Inter-hospital, Virtual Multidisciplinary Tumor Board on Prostate Cancer.

BACKGROUND/AIM: At present, multidisciplinary tumor boards (MDTB) are considered best practice in oncology. However, web-based virtualization of MDTB may increase participation in meetings, the number of cases discussed, and adherence to guidelines, deliver better treatment, and eventually improve outcomes for patients with prostate cancer. PATIENTS AND METHODS: This is an observational study focused on exploring the structuring process and implementing a multi-institutional virtual MDTB in Sicily, Italy. Other endpoints included the analysis of cooperation between participants, adherence to guidelines, patient outcomes, and patient satisfaction. RESULTS: Overall, 126 patients were referred to the virtual MDTB for a total of 302 cases discussed in an 18-month period. Nearly 45% of cases were referred from general hospitals or tertiary centers, 38% from comprehensive cancer centers, and only 17% from academic ones. Most health professional participants (95%) reported eliminating geographical barriers and consequently reducing costs and saving time as key advantages of virtual meetings over face-to-face ones. Using a specifically designed platform for virtual MDTBs was another excellent point, especially to geolocate clinical trials and time-lapse data storage. The majority of referred patients had stage T 3-4 prostate cancer (79%). Overall, 71% of proposals discussed were approved unchanged, while 19% changed after the virtual MDTB discussion. Debated points were mostly radiologic, surgical, medical, or radiation treatment-related issues. In particular, the prescriptive appropriateness of positron emission tomography with 68Ga-prostatic specific membrane antigen, newer drugs, radiation versus surgical approach, stage T3-4 cases, and adjuvant therapy represented the most debated issues. The proposed diagnostic and/or therapeutic options were controlled for adherence to the guidelines and/or updated scientific evidence. Overall, 98% of approved proposals and changes were in line with the guidelines. Overall, most participants felt virtual MDTB was very useful and case discussions led to a major change of strategy in 19% of cases. CONCLUSION: Virtual MDTBs are a very useful way to achieve best management of prostate cancer while saving time and fostering cooperation.

Post-operative hypofractionated radiotherapy for prostate cancer: a mono-institutional analysis of toxicity and clinical outcomes.

BACKGROUND: As the use of hypofractionation has spread in the setting of curative prostate radiotherapy, few data are available in the post-operative scenario. This study reports a mono-institutional experience of moderate post-operative hypofractionated radiotherapy for prostate cancer. METHODS: In February 2021, we retrospectively assessed the outcomes of 129 patients who received between April 2013 and May 2020 hypofractionated post-operative radiotherapy using Helical Tomotherapy. Toxicity was assessed using CTCAE criteria v4.0. Survival endpoints were calculated with Kaplan-Meier method. RESULTS: Median age and follow-up were, respectively, 67 years and 43 months. Adjuvant and salvage treatment were delivered to 63.5% and 36.4% of patients to a median total dose of 63.8 Gy (61.6-65.25 Gy) in 29 fractions (2.12-2.25 Gy/fraction). Pelvic lymph-nodes irradiation was performed in 67.4% of cases. ADT was added in 50%. Acute toxicity was: G1 and G2 GU events in 36% and 9.3% of cases; G1 and G2 GI events in 29.4% and 13.9%. Late GU toxicity occurred in 12.4% of cases: 3.1% G1, 7.7% G2 and 1.5% G3 events; GI toxicity consisted of 1.5% G1 and 7.7% G2 events. Biochemical relapse occurred in 26.3% of cases, recording no significant differences between adjuvant and salvage (p = 0.67), with 4- and 5-years bRFS rates of 78.7% and 75.6%. Two patients died of progressive disease and eight for non-oncological causes resulting in 3-years overall survival and cancer-specific survival rates of 98% and 98.4%. CONCLUSIONS: Our experience supports the use of moderate hypofractionation for prostate bed radiotherapy, with minimal toxicity and promising results in terms of clinical outcomes.

A prospective observational study on oral administration of Ellagic Acid and Annona Muricata in patients affected by non-muscle invasive bladder cancer not undergoing maintenance after 6-week intravesical prophylaxis.

INTRODUCTION: BCG and MMC shortage and Covid-19 pandemic, more recently, limit accessibility to maintenance regimen in intravesical prophylaxis against recurrence of non-muscle invasive bladder cancer (NMIBC). Ellagic acid (EA) and Annona muricata (AM) exert antitumor activity against different human tumours. An observational prospective study on the prophylactic effect of oral administration of EA+AM in patients avoiding maintenance regimen is presented. MATERIALS AND METHODS: Patients affected by NMIBC and not undergoing maintenance after a 6-week course of intravesical prophylaxis with MMC or BCG were entered. Tis and very high-risk tumours were excluded. After informed consent, the patients were subdivided in relation to the oral assumption or not of EA (100 mg) plus AM (100 mg), daily for 6 months. All patients were submitted to 3-month cytology and cystoscopy. RESULTS: 162 (90%) of 180 entered patients are evaluable, 90 and 72 receiving or not EA+AM. No difference emerged in patients' characteristics between the two groups. BCG was given in 86 (54%) and chemotherapy in 74 (46%) patients. The recurrence free rate at 3, 6 and 12 months in patients assuming or not EA was 96.5% versus 84.6% (p = 0.003), 85.4% versus 64.8% (p = 0.005) and 74.2% versus 60.6% (p = 0.246), respectively. The recurrence free survival at 12 months in patients assuming or not EA was 63.0% versus 34.5% (p < 0.0001). DISCUSSION AND CONCLUSIONS: Our study suffers several limits: not randomized trial although prospective, limited number of patients and short follow-up, nevertheless it shows the prophylactic effect of oral EA+AM in absence of maintenance after intravesical chemotherapy or immunotherapy induction.

Multicentre International Study for the Prevention with iAluRil of Radio-induced Cystitis (MISTIC): A Randomised Controlled Study.

BACKGROUND: Radiation-induced cystitis is a common side effect of radiotherapy (RT) to the pelvic area. Hyaluronic acid (HA) and chondroitin sulfate (CS) are components of the urothelial mucosa and positive results have been obtained for intravesical HA/CS instillations for the treatment of urinary tract infections and bladder pain syndrome. HA/CS may also have a protective effect against RT bladder toxicity. OBJECTIVE: To investigate whether HA and CS protect the urothelium during RT, alleviate lower urinary tract symptoms, and improve quality of life. DESIGN SETTING AND PARTICIPANTS: This multicentre randomised controlled trial was conducted across seven centres in four countries. Male patients aged ≥18 yr scheduled to undergo primary intensity-modulated radiotherapy for localised prostate cancer were enrolled. INTERVENTION: Patients were randomised to intravesical HA/CS plus an oral formulation of curcumin, quercetin, HA, and CS (group A) or no treatment (group B). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was absolute changes from baseline to follow-up in urinary domain scores for the Expanded Prostate Cancer Index Composite (EPIC), the International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS), and the EuroQol Group EQ-5D-5L questionnaire. Data analysis for efficacy and safety outcomes was performed using an intention-to-treat (ITT) approach; the ITT population was defined as all randomised patients. RESULTS AND LIMITATIONS: Of 57 patients screened, 49 were enrolled and randomly assigned to either active treatment (group A, n = 25) or the control (group B, n = 24). Three patients in the control group withdrew after randomisation. Changes from baseline to 12 mo were worse in the control group for subtotal scores for urinary symptoms and impact of symptoms on quality of life and for the total score (p = 0.05, p = 0.003, and p = 0.008, respectively). There was a significant time × group interaction in favour of active treatment for the incontinence symptom score (p = 0.011) and bother score (p = 0.017). The absence of a sham procedure and/or placebo is the main limitation. CONCLUSIONS: Our results suggest that intravesical HA/CS in combination with an oral formulation may reduce urinary symptoms and improve QoL at short-term (1 yr) follow-up. PATIENT SUMMARY: We investigated whether hyaluronic acid (HA) and chondroitin sulfate (CS) have a protective effect against the bladder toxicity of radiotherapy for prostate cancer. HA/CS used for weekly bladder irrigation for 6 wk and given orally with curcumin and quercetin for 12 wk reduced urinary incontinence symptoms and bother measured at 1-year follow-up. This may hold promise as a preventive treatment if the results are confirmed in further trials.

Virtual Clinical and Precision Medicine Tumor Boards-Cloud-Based Platform-Mediated Implementation of Multidisciplinary Reviews Among Oncology Centers in the COVID-19 Era: Protocol for an Observational Study.

BACKGROUND: Multidisciplinary tumor boards play a pivotal role in the patient-centered clinical management and in the decision-making process to provide best evidence-based, diagnostic, and therapeutic care to patients with cancer. Among the barriers to achieve an efficient multidisciplinary tumor board, lack of time and geographical distance play a major role. Therefore, the elaboration of an efficient virtual multidisciplinary tumor board (VMTB) is a key point to successfully obtain an oncology team and implement a network among health professionals and institutions. This need is stronger than ever during the COVID-19 pandemic. OBJECTIVE: This paper presents a research protocol for an observational study focused on exploring the structuring process and the implementation of a multi-institutional VMTB in Sicily, Italy. Other endpoints include analysis of cooperation between participants, adherence to guidelines, patients' outcomes, and patient satisfaction. METHODS: This protocol encompasses a pragmatic, observational, multicenter, noninterventional, prospective trial. The study's programmed duration is 5 years, with a half-yearly analysis of the primary and secondary objectives' measurements. Oncology care health professionals from various oncology subspecialties at oncology departments in multiple hospitals (academic and general hospitals as well as tertiary centers and community hospitals) are involved in a nonhierarchic manner. VMTB employs an innovative, virtual, cloud-based platform to share anonymized medical data that are discussed via a videoconferencing system both satisfying security criteria and compliance with the Health Insurance Portability and Accountability Act. RESULTS: The protocol is part of a larger research project on communication and multidisciplinary collaboration in oncology units and departments spread in the Sicily region. The results of this study will particularly focus on the organization of VMTBs, involving oncology units present in different hospitals spread in the area, and creating a network to allow best patient care pathways and a hub-and-spoke relationship. The present results will also include data concerning organization skills and pitfalls, barriers, efficiency, number, and types with respect to clinical cases and customer satisfaction. CONCLUSIONS: VMTB represents a unique opportunity to optimize patient management through a patient-centered approach. An efficient virtualization and data-banking system is potentially time-saving, a source for outcome data, and a detector of possible holes in the hull of clinical pathways. The observations and results from this VMTB study may hopefully be useful to design nonclinical and organizational interventions that enhance multidisciplinary decision-making in oncology. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26220.

Sexual dysfunction in dialytic patients. A prospective cross-sectional observational study in two hemodialysis centers.

OBJECTIVES: Incidence and prevalence of patients in dialytic therapy increased considerably in recent years. The onset of new issues, once overshadowed, linked to a lower quality of life like sexual dysfunction became increasingly common. The first study in this area, dating back to the 1970s, shows the high prevalence of sexual dysfunction among patients in dialytic therapy of both sexes. Later studies proved an association of sexual dysfunction with psyche disorders, anxiety, depression and lack of self-confidence. The aim of this study is to describe the incidence of male and female sexual main dysfunctions, the latter not least in literature, in patients in hemodialytic therapy. With this aim two dialytic centers have been compared, one located in northern Italy and one in southern Italy, and the different prevalence has been compared to the general population. METHODS: We conducted a prospective cross-sectional observational study in patients undergoing dialytic therapy in two hemodialysis centers, one located in Palermo and one in Lecco. Male sexual dysfunction was investigated by the International Index of Erectile Function-15 (IIEF15) questionnaire and the Premature Ejaculation Diagnotic Tool (PEDT) questionnaire, and the female dysfunction by Female Sexual Function Index (FSFI) questionnaire. Criteria for inclusion in our study were: age < 75 years and dialytic age > 3 months; exclusion criteria were: advanced cancer diseases, life expectancy < 6 months, previous urological manipulation, anti-androgenic therapy, sexual dysfunction unrelated to kidney disease, psychiatric disorders. Data were compared with mean-standard deviation (SD) and with the variance analysis (ANOVA). A value of p < 0.05 is considered significant. Discrete data were analyzed with contingency analysis. A chi2 < 0.05 was considered significant. RESULTS: Data of 78 patients have been collected. Mean age and dialytic time were 54 ± 12 years and 42 ± 35 month; 33 patients were from Palermo and 24 from Lecco; 21 patients were excluded. Age and dialytic age of the two subgroups did not demonstrate statistically significant differences. Between the two centers there was a statistically significant difference (p < 0.005) in the distribution of basic nephropathy: an higher incidence of diabetic and obstructive nephropathy has been observed in the southern center compared to northern center, while glomerulonephritis and polycystic kidney disease had an higher incidence in the northern center compared to southern one. The main sexual dysfunctions in both sexes, erectile dysfunction (ED) and premature ejaculation (PE) in men and orgasm disorder and pelvic pain in women, have been investigated. ED was present in 70%  of hemodialyzed patients, which is an higher incidence compared to the general population. The severity of ED between patients of the two groups was significantly different (chi2 < 0.001) with higher incidence of moderate/severe forms in northern Italy. The score, in addition to discrete data (severe, moderate, mild, absence), of ED was significantly different (p < 0.001) between patients of the two centers (22 ± 7 Palermo vs. 9 ± 8, Lecco). The PE was absent in 20 patients (54%), present in 12 patients (32%) and probable in 5 patients (14%) (scores of 7.6 ± 4.0 and 8.9 ± 6.8, respectively in Palermo and Lecco patients). For women, orgasmic dysfunction was severe in 10 patients (50%), mild in 4 patients (20%), very mild in 5 patients (25%), while it was normal in 1 patient (5%), with a statistically significant difference (p< 0.05) between Palermo and Lecco patients (3.0 ± 1.4 vs 1.2 ± 2.0). Sexual pain in women was severe in 11 patients (55%), moderate in 4 patients (20%) and mild in 5 patients (25%). Sexual pain was present in all patients (p < 0.05). CONCLUSIONS: Regardless of sex, sexual dysfunction is one of the most common side effect in patients with end stage renal disease in dialytic therapy. Our study confirms literature data. The growing number of the dialytic population with sexual disorders needs specialist support to improve quality of life of these patients.

Fibronectin urothelial gene expression as a new reliable biomarker for early detection of local toxicity secondary to adjuvant intravesical therapy for non-muscle invasive bladder cancer.

BACKGROUND: A marker of urothelial damage could be helpful for early detection and monitoring of local toxicity due to intravesical therapy for non-muscle invasive bladder cancer (NMIBC). The aim of the study was to investigate the correlation between fibronectin (FN) gene expression in bladder washings and local toxicity secondary to adjuvant intravesical therapy. MATERIALS AND METHODS: Patients undergoing adjuvant intravesical therapy for NMIBC and age-matched healthy patients were enrolled. Real time polymerase chain reaction was performed to analyze FN expression in bladder washings. Local toxicity was classified as: 0-1 mild (no medical therapy), 2 moderate (medical therapy and/or instillation postponed), 3 severe (discontinuation of therapy). RESULTS: Seventy-two patients and 21 controls entered the study. A useful pellet was obtained in 58 patients and 18 controls. Intravesical Bacillus Calmette-Guerin (BCG), Epirubicin and Mitomycin C was offered to 69%, 13.8% and 17.2% of patients respectively. Compared with healthy controls (FN = 1.0 fold), overall median FN expression before adjuvant intravesical therapy was 1.73 fold [interquartile range (IQR) 0.8-2.3], while during therapy median FN expression increased to 3.41 (IQR: 1.6-6.1) fold. Considering 40 intermediate and high-risk patients undergoing intravesical BCG, median FN expression before adjuvant treatment was 1.92 [(IQR: 1.0-2.7) fold, increasing up to 4.1 (IQR: 1.9-6.6) during therapy. In more detail, FN increased during BCG therapy, showing a median expression of 4.22 (IQR: 2.2-5.5) and 6.16 (IQR: 2.6-8.7) fold in presence of grade 2 and 3 toxicity respectively, while remaining more or less stable in asymptomatic patients. After receiver operating characteristic curve analysis, FN value of 3.6 fold resulted, corresponding to 75% sensitivity and 69% specificity to predict grade 2-3 toxicity events (area under the curve 0.74, 95% confidence interval 0.63-0.85, p = 0.001). CONCLUSION: Our study validated the correlation between FN expression and urothelial damage. BCG seems to induce a urothelial activation with FN overexpression during adjuvant intravesical therapy. Grade of toxicity was related to FN expression.

Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guérin immunotherapy for T1G3/HG bladder cancer.

PURPOSE: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC). MATERIALS AND METHODS: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. RESULTS: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55). CONCLUSION: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.

NEPA as antiemetic prophylaxis after failure of 5HT3-RA plus dexamethasone in patients receiving carboplatin and gemcitabine chemotherapy: A monocentric real-life experience.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients' quality of life during the therapy. NEPA is an oral fixed combination of netupitant, a highly-selective NK1-RA and palonosetron, a 5HT3-RA, approved for the prevention of acute and delayed CINV. The aim of this study was to evaluate the efficacy and safety of NEPA with dexamethasone for CINV prophylaxis in the challenging setting of carboplatin and gemcitabine combination chemotherapy, after failure of prophylaxis with 5HT3 receptor antagonist. METHODS: Eligible patients were undergoing carboplatin and gemcitabine combination chemotherapy for metastatic non-small cell lung cancer (NSCLC), ovarian cancer or urothelial cancer and experienced nausea and/or vomiting after the first cycle of chemotherapy, despite an antiemetic prophylaxis with a 5HT3-RA and dexamethasone. Primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) obtained with NEPA, during the overall phase (0-120 h), after the start of chemotherapy. RESULTS: During the first cycle of chemotherapy, 15 out of 30 (50%) patients did not properly control CINV with a 5HT3-RA plus dexamethasone used as primary antiemetic prophylaxis and then were switched to NEPA from the subsequent cycle. During NEPA administration, 13 out of 15 patients (86.7%) achieved an overall CR (no emesis, no rescue medication). Antiemetic treatment with NEPA was very well tolerated with only two patients (13.3%) that experienced a grade 1 TEAE. CONCLUSIONS: Our experience showed that NEPA has proven to be very effective and well tolerated in the prophylaxis of CINV induced by carboplatin-based chemotherapy.

Is Kelami's Method Still Useful in the Smartphone Era? The Virtual 3-Dimensional Reconstruction of Penile Curvature in Patients With Peyronie's Disease: A Pilot Study.

BACKGROUND: Peyronie's disease is an idiopathic fibrotic disease affecting the penile tunica albuginea. Among other resulting deformities, the more common penile curvature should be assessed preferentially with in-office goniometric estimation after pharmacologically induced erection, although clearly invasive and uncomfortable. AIM: In the present pilot study, we investigated the usefulness for the patient and the surgeon of a 3-dimensional (3D) reconstruction of the penile curvature obtained through photogrammetry software in clinical evaluation and surgical planning. METHODS: Enrolled patients received alprostadil 10 µg by intracavernous injection. Then, the medical personnel took a sequence of up to 50 photographs in orthostatism via a smartphone and processed them to obtain a 3D model of the whole groin area with 3DF Zephyr free software (3Dflow SRL, Verona, Italy), to take measurements of the penile curvature with MeshLab software (National Research Council of Italy, Rome, Italy) and to simulate the results after corporoplasty with Blender software (Blender Foundation, Amsterdam, the Netherlands). Finally, we submitted a 1-5 Likert scale to patients and surgeons investigating their satisfaction with the use of the 3D model during preoperative counseling, surgical planning, and the esthetic results after surgery. OUTCOMES: We investigated the patient and surgeon satisfaction with the use of the 3D model in understanding/evaluating the pathology and the surgical planning during the preoperative visit and the satisfaction with the final esthetic results in relation to the preoperative model itself. RESULTS: 4 patients were included. The median photographs acquisition and computer processing time were 39 seconds and 347.5 minutes, respectively. All the patients and surgeons involved gave a score of ≥4 to all the items investigated. CLINICAL IMPLICATIONS: The 3D model of the penile curvature is very useful both to the patient and the surgeon to understand the severity of the disease and the possible surgical management. STRENGTH & LIMITATIONS: This is a pilot study including only 4 cases, but it is the first experience in which the patients with Peyronie's disease had the possibility to see a virtual 3D model of their penile curvature and final esthetic results after corporoplasty, based on 3 freely available computer applications. CONCLUSION: Our pilot study has shown that it is possible to quickly obtain a sequence of photographs to create an accurate virtual 3D model of the penis of patients with Peyronie's disease, helping the patients and the surgeon during preoperative counseling and surgical planning. Pavone C, Abrate A, Altomare S, et al. Is Kelami's Method Still Useful in the Smartphone Era? The Virtual 3-Dimensional Reconstruction of Penile Curvature in Patients With Peyronie's Disease: A Pilot Study. J Sex Med 2021;18:209-214.

How Can the COVID-19 Pandemic Lead to Positive Changes in Urology Residency?

The COVID-19 outbreak, in a few weeks, overloaded Italian hospitals, and the majority of medical procedures were postponed. During the pandemic, with hospital reorganization, clinical and learning activities performed by residents suffered a forced remodulation. The objective of this study is to investigate how urology training in Italy has been affected during the COVID-19 era. In this multi-academic study, we compared residents' training during the highest outbreak level with their previous activity. Overall 387 (67.1%) of the 577 Italian Urology residents participated in a 72-h anonymous online survey with 36 items sent via email. The main outcomes were clinical/surgical activities, social distancing, distance learning, and telemedicine. Clinical and learning activity was significantly reduced for the overall group, and after categorizing residents as those working only in COVID hospitals, both "junior" and "senior" residents, and those working in any of three geographical areas created (Italian regions were clustered in three major zones according to the prevalence of COVID-19). A significant decrease in outpatient activity, invasive diagnostic procedures, and endoscopic and major surgeries was reported. Through multivariate analysis, the specific year of residency has been found to be an independent predictor for all response modification. Being in zone 3 and zone 2 and having "senior" resident status were independent predictors associated with a lower reduction of the clinical and learning activity. Working in a COVID hospital and having "senior" resident status were independent predictors associated with higher reduction of the outpatient activity. Working in zone 3 and having "senior" resident status were independent predictors of lower and higher outpatient surgical activity, respectively. Working in a COVID hospital was an independent predictor associated with robotic surgical activity. The majority of residents reported that distance teaching and multidisciplinary virtual meetings are still not used, and 44.8% reported that their relationships with colleagues decreased. The COVID-19 pandemic presents an unprecedented challenge, including changes in the training and education of urology residents. The COVID era can offer an opportunity to balance and implement innovative solutions that can bridge the educational gap and can be part of future urology training.

Stereotactic Radiotherapy for the Treatment of Patients With Oligo-progressive Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor: Data From the Real World.

AIM: This retrospective observational study evaluated the role of hypo-fractionated stereotactic radiotherapy (SRT) in patients with oligo-progressive metastatic renal cell carcinoma (mRCC) treated with first-line oral tyrosine kinase inhibitors (TKI). Data on local control, delay of further progression, and safety are reported. PATIENTS AND METHODS: Between January 2010 and December 2016, 28 patients with mRCC who showed oligo-progressive disease while receiving first-line pazopanib were treated with hypofractionated SRT to progressive metastatic sites to delay the change of systemic therapy. First and second progression-free survival (PFS-1 and PFS-2) were recorded, as well as objective response and toxicity. RESULTS: After pazopanib therapy, nine partial remissions (32%), 12 stable disease (43%) and seven progressions (25%) were recorded. The median time to progression from first-line pazopanib until oligo-progression was 9.45 months (PFS-1 range=2-30 months). Seventeen patients (61%) showed progression at pre-existing tumor sites, and 11 patients (39%) showed the appearance of new metastases. Progression-free survival after radiation therapy was 4.55 months (PFS-2 range=1-11 months). PFS-1 plus PFS-2 was 14.0 months (range=3-41 months). Severe grade 3-4 toxicities were seen only occasionally. CONCLUSION: Patients with oligo-progressive mRCC treated with first-line pazopanib may benefit from hypo-fractionated high-dose SRT at progressing sites achieving a further increase in median progression-free survival. Further studies and prospective validation are required to establish if this minimally invasive approach may have a positive impact on overall survival and reported outcomes.

Sildenafil orodispersible film in the treatment of erectile dysfunction after radical prostatectomy: A single-centre open-label uncontrolled trial.

Phosphodiesterase-5 inhibitors are the first-line therapy for erectile dysfunction (ED) after radical prostatectomy (RP). This single-centre open-label uncontrolled study evaluated the efficacy and safety of the new sildenafil orodispersible film (ODF) in ED treatment after RP. Sildenafil 100 mg ODF was administered twice a week for 3 months to patients under 75 years of age, with a Framingham cardiovascular risk score < 20% and a pre-operative International Index of Erectile Function (IIEF)-5 score ≥ 17, who had undergone open RP between 2016 and 2018. Erectile function was assessed pre-operatively, post-operatively and after treatment through the IIEF-5 score, the Sexual Encounter Profile Question (SEP-Q) 2 and SEP-Q3; adverse events (AE) were also investigated after 3 months. A total of 65 patients with a median (25th-75th percentile) post-operative IIEF-5 score of 8 (7-9) were treated. Nine (13.8%) patients reported AE of mild/moderate grade and discontinued treatment. A significant IIEF-5 score median (25th-75th percentile) increase of 10 (0-12) was found after treatment in the other 56 patients (p < .001). Sildenafil 100 mg ODF was effective in ED after RP in terms of improved IIEF-5 score and improved SEP-Q2 and SEP-Q3 in 67.9% of patients. It could represent a valid alternative for those patients with low compliance to tablet intake.

Does Smoking Cessation at Primary Diagnosis Reduce the Recurrence Risk of Nonmuscle-Invasive Bladder Cancer? Results of a Prospective Study.

INTRODUCTION: Evidence that smoking cessation at first diagnosis of nonmuscle-invasive bladder cancer (NMIBC) reduces the risk of recurrence is lacking. The aim of our prospective study was to analyze the association between patients' changes in smoking habits after diagnosis and recurrence-free survival (RFS). PATIENTS: After transurethral resection of primary NMIBC, patients were classified as "ex-smokers," i.e., those definitively stopping, and as "active smokers," i.e., those continuing or restarting to smoke. Smoking status was reassessed every 3 months during the first year and every 6 months thereafter. Data on patients' demographics, smoking status, tumor characteristics, treatments, and follow-up were collected. Statistical analysis was performed adopting SPSS 15.0.1 and R3.4.2 software. RESULTS: Out of 194 patients, 67 (34.5%) quit smoking after the diagnosis, while 127 (65.5%) did not. The clinical and pathological characteristics were homogeneously distributed. At a median follow-up of 38 months, 106 patients (54.6%) recurred, 33 (49.2%) ex- and 73 (60.3%) active smokers with a 3-year RFS of 42.3 and 50.7%, respectively (p = 0.55). No statistically significant association between recurrence, pathological features of the primary tumor, and patient smoking habits after diagnosis was detected. Results were not statistically influenced by the intensity (cigarette/day) and duration (years) of smoking. In multivariate analysis, cigarette smoking cessation at diagnosis did not significantly reduce tumor recurrence. CONCLUSION: In our prospective study, more than half of our patients recurred at 3 years. In multivariate analysis, smoking cessation did not significantly reduce tumor recurrence. However, the 8.4% reduction in favor of the ex-smokers suggests the need of larger studies with longer follow-ups. Surprisingly, only 35% of smokers definitively quit after diagnosis. The urologists should play a more active role to persuade the patients to stop smoking at first cancer diagnosis.

Segmental ureterectomy vs. radical nephroureterectomy for ureteral carcinoma in patients with a preoperative glomerular filtration rate less than 90 ml/min/1.73 m2: A multicenter study.

OBJECTIVES: To compare segmental ureterectomy (SU) and radical nephroureterectomy (RNU) in terms of overall survival (OS) and impact on postoperative renal function in patients treated for upper tract urothelial carcinoma (UTUC) of the ureter with preoperatively reduced estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: We retrospectively collected the data of consecutive patients treated for UTUC, in 6 Italian tertiary referral centers, from 2003 to 2013, and analyzed those treated with RNU or SU for ureteral cancer and with a preoperative eGFR <90 ml/min/1.73m2. The primary outcome was to compare the postoperative eGFR variation and the OS according to the surgical technique chosen. RESULTS: Out of 521 patients with UTUC, 228 patients had preoperative reduced eGFR. Out of these patients, 93 had ureteral cancer and were included in the primary analyses - 67 (72.0%) treated with RNU and 26 (28.0%) with SU. Preoperative characteristics were similar in the 2 groups. The overall median follow-up period was 26.5 months. A nonsignificant postoperative eGFR decrease of 3.0 ml/min/1.73m2 was found overall (P = 0.094), with nonsignificant difference between the 2 groups (P = 0.735). A comparable 5-year OS was calculated for RNU and SU patients (P = 0.99). CONCLUSIONS: The type of surgery (SU vs. RNU) has a low impact on postoperative renal function and OS in patients with ureteral cancer and preoperative eGFR <90 ml/min/1.73m2. The indications for kidney sparing surgery for UTUC should be based on the surgical and oncological risks in these patients.

Type 2 diabetes mellitus predicts worse outcomes in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

OBJECTIVES: The aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB). MATERIALS AND METHODS: A total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival. RESULTS: A total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20-1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99-1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio. CONCLUSIONS: Given the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted.

Can We Clinically Distinguish Anejaculation From Retrograde Ejaculation in Patients on α1A-Blockers Therapy for Lower Urinary Tract Symptoms?

OBJECTIVE: To investigate the physiopathology of ejaculatory disorders (EjD) and discriminate between retrograde ejaculation (REj) and anejaculation (AEj) induced by α1A-blockers, through the association between the mean postorgasm seminal vesicle volume and the presence of sperm in midstream urine, in patients with moderate-to-severe lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement. MATERIALS AND METHODS: Therapy-naïve male patients with LUTS and without previous EjD were treated with α1A-blockers. Pre- and post-treatment EjD were investigated through question 4 of the 4-item Male Sexual Function questionnaire and the Male Sexual Health Questionnaire for Ejaculatory Dysfunction Short Form (MSHQ-EjD-SF). After 12 weeks, postorgasm urine was collected for sperm count and seminal vesicle volume was calculated through transrectal ultrasound. RESULTS: All 42 patients reported with EjD after treatment with α1A-blockers: 4-item Male Sexual Function questionnaire and MSHQ-EjD-SF Q4 scores were significantly higher (P <.001) and MSHQ-EjD-SF Q1-3 score was significantly lower (P <.001) than before. Postorgasm seminal vesicle volume was significantly higher in patients with postorgasm sperm-negative urine (AEj), and lower in patients with postorgasm sperm-positive urine (REj; P <.001). CONCLUSION: We clearly demonstrated an association between the presence of sperm in the midstream urine and seminal vesicle volume after orgasm, strongly confirming and differentiating the hypothesis of a dual etiology for EjD (REj vs AEj) secondary to α1A-blockers therapy for LUTS.