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.

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.

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.

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.

Radium-223 treatment in castration resistant bone metastatic prostate cancer. Should be the primary tumor always treated?

INTRODUCTION: Radium-223 (223Ra) improves symptoms and survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). STUDY AIM: To evaluate the impact of a previous radical prostatectomy (RP) on the outcome of 223Ra therapy in mCRPC patients. The primary prostate tumor left untreated could progress during 223Ra treatment. MATERIALS AND METHODS: mCRPC symptomatic patients treated with 223Ra were enrolled. Luteinizing Hormone-Releasing Hormone analogue was maintained. No other anticancer therapy was given. 223Ra was administered i.v. at the dose of 55 kBq/kg every 4 weeks for 6 cycles. Patients were stratified according to previous RP or not. Hematological toxicity was monitored. Statistical analysis of 223Ra discontinuations, progressions, and deaths were performed. RESULTS: Forty-four patients were enrolled, 16 (36.4%) previously received RP, 5 (11.3%) prostate radiotherapy and 23 (52.3%) maintained the primary prostate tumor after local treatment. All patients presented only bone metastases, 24 patients (54.5%) had more than 20. Twenty-six (59.1%) patients were treated after first or second line systemic chemotherapy. Treatment interruptions occurred in 14 patients (50%) with prostate and in 4 (25%) without (P = 0.04). After a median follow-up of 18 months (6-30 months), 15 (53.6%), and 7 (43.7%) progressions (P = 0.34) and 13 and 1 (6.2%) deaths (P = 0.04) occurred in patients with and without prostate respectively. CONCLUSION: The presence of the primary prostate tumor seems to play a detrimental role in mCRPC patients undergoing 223Ra treatment in absence of other concomitant anticancer therapy. On the other hand a previous RP might play a protective role.

Clinical and biochemical markers of visceral adipose tissue activity: Body mass index, visceral adiposity index, leptin, adiponectin, and matrix metalloproteinase-3. Correlation with Gleason patterns 4 and 5 at prostate biopsy.

CONTEXT: The correlation between aggressive prostate cancer and obesity mainly based on body mass index (BMI) and pathology after surgery remains controversial. AIMS: The aim of the study was to correlate BMI, visceral adiposity index (VAI), and the plasmatic levels of leptin, adiponectin, and matrix metalloproteinase-3 (MMP-3), and biomarkers of adipose tissue function, with the detection of Gleason patterns 4 and 5 at biopsy. SUBJECTS AND METHODS: Consecutive patients with prostate cancer at 12-core transrectal biopsy were enrolled. BMI, waist circumference (WC), blood samples to evaluate the plasmatic levels of triglycerides (TG) and high-density lipoproteins (HDL), adiponectin, leptin, and MMP-3 were obtained immediately before biopsy. The VAI was calculated according to the formula: WC/(39.68 + [1.88 × BMI]) × TG/1.03 × 1.31/HDL. RESULTS: One hundred and forty-nine patients were entered. The median PSA, BMI, and VAI were 10.0 ng/ml, 27.6 kg/m2, and 4.6, respectively. Gleason patterns 4 or 5 were detected in 68 (45.6%) patients; in 15 (41.7%), 31 (44.9%), and 22 (50.0%) among normal weight, overweight, and obese patients, respectively (P = 0.55). The statistical analysis did not show any significant correlation between BMI, VAI, the plasmatic levels of leptin, adiponectin, MMP-3, and the detection of Gleason patterns 4 and 5 at biopsy. A statistically significant association emerged with older age (P = 0.017) and higher PSA values (P = 0.02). CONCLUSION: We did not find any association between BMI, VAI, the plasmatic levels of adiponectin, leptin, and MMP-3 and the detection of Gleason patterns 4 and 5 at prostate biopsy.