New minimally invasive solutions for Benign Prostatic Obstruction (BPO) management: A position paper from the UrOP (Urologi Ospedalità Gestione Privata).

To the Editor, In recent years, alternative solutions have been proposed to obtain effective results comparable to TURP, which is currently considered the gold standard, and laser vapo-enucleation techniques (1, 2), but with the possibility of maintaining sexual functions. In recent years there has been a growing trend towards ejaculation preservation. Although the results of TURP (3), and most laser enucleation techniques are undoubted in the Benign Prostatic Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS) management, they often lack in the preservation of ejaculation. All the alternative recently proposed interventions (Rezum, AquaBeam, Urolift, TPLA, i-TIND, LEST) are procedures considered by some authors to be promising in both managing BPO and preserving sexual functions. However, all these methods are limited by a lack of long-term follow-up that would evaluate the efficacy over time, possible complications related to the method and the correct patient selection for a specific method. The aim of this letter is to summarize the available evidence and provide clinicians with practical recommendations on the use of the brand new minimally invasive techniques for the management of BPO. [...].

Thermal ablation for small renal masses: Identifying the most appropriate tumor size cut-off for predicting perioperative and oncological outcomes.

OBJECTIVES: To test TRIFECTA achievement [1) absence of CLAVIEN-DINDO ≥3 complications; 2) complete ablation; 3) absence of ≥30% decrease in eGFR] and local recurrence rates, according to tumor size, in patients treated with thermal ablation (TA: radiofrequency [RFA] and microwave ablation [MWA]) for small renal masses. METHODS: Retrospective analysis (2008-2020) of 432 patients treated with TA (RFA: 162 vs. MWA: 270). Tumor size was evaluated as: 1) continuously coded variable (cm); 2) tumor size strata (0.1-2 vs. 2.1-3 vs. 3.1-4 vs. >4 cm). Multivariable logistic regression models and a minimum P-value approach were used for testing TRIFECTA achievement. Kaplan-Meier plots depicted local recurrence rates over time. RESULTS: Overall, 162 (37.5%) vs. 140 (32.4%) vs. 82 (19.0%) vs. 48 (11.1%) patients harboured, respectively, 0.1 to 2 vs. 2.1 to 3 vs. 3.1 to 4 vs. >4 cm tumors. In multivariable logistic regression models, increasing tumor size was associated with higher rates of no TRIFECTA achievement (OR:1.11; P< 0.001). Using a minimum P-value approach, an optimal tumor size cut-off of 3.2 cm was identified (P< 0.001). In multivariable logistic regression models, 3.1 to 4 cm tumors (OR:1.27; P< 0.001) and >4 cm tumors (OR:1.49; P< 0.001), but not 2.1 to 3 cm tumors (OR:1.05; P= 0.3) were associated with higher rates of no TRIFECTA achievement, relative to 0.1 to 2 cm tumors. The same results were observed in separate analyses of RFA vs. MWA patients. After a median (IQR) follow-up time of 22 (12-44) months, 8 (4.9%), 8 (5.7%), 11 (13.4%), and 5 (10.4%) local recurrences were observed in tumors sized 0.1 to 2 vs. 2.1 to 3 vs. 3.1 to 4 vs. >4 cm, respectively (P= 0.01). CONCLUSION: A tumor size cut-off value of ≤3 cm is associated with higher rates of TRIFECTA achievement and lower rates of local recurrence over time in patients treated with TA for small renal masses.

Carboplatin-based adjuvant chemotherapy versus observation after radical cystectomy in patients with pN1-3 urothelial bladder cancer.

PURPOSE: To test the impact of carboplatin-based ACT on overall survival (OS) in patients with pN1-3 cM0 BCa. METHODS: A retrospective analysis was conducted on 1057 patients with pTany pN1-3 cM0 urothelial BCa treated with or without carboplatin-based ACT after radical cystectomy and bilateral lymph-node dissection between 2002 and 2018 at 12 European and North-American hospitals. No patient received neoadjuvant chemotherapy or radiation therapy. Only patients with negative surgical margins at surgery were included. A 3:1 propensity score matching (PSM) was performed using logistic regression to adjust for baseline characteristics. Univariable and multivariable Cox regression analyses were used to predict the effect of carboplatin-based ACT on OS. The Kaplan-Meier method was used to display OS in the matched cohort. RESULTS: Of the 1057 patients included in the study, 69 (6.5%) received carboplatin-based ACT. After PSM, 244 total patients were identified in two cohorts that did not differ for baseline characteristics. Death was recorded in 114 (46.7%) patients over a median follow-up of 19 months. In the multivariable Cox regression analyses, increasing age at surgery (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.06, p < 0.001) and increasing number of positive lymph nodes (HR 1.06, 95% CI 1.01-1.07, p = 0.02) were independent predictors of worse OS. The delivery of carboplatin-based ACT was not predictive of improved OS (HR 0.67, 95% CI 0.43-1.04, p = 0.08). The main limitations of this study are its retrospective design and the relatively low number of patients involved. CONCLUSIONS: Carboplatin-based might not improve OS in patients with pN1-3 cM0 BCa. Our results underline the need for alternative therapies for cisplatin-ineligible patients.

Impact of Perioperative Immunonutrition on Complications in Patients Undergoing Radical Cystectomy: A Retrospective Analysis.

INTRODUCTION: Radical cystectomy (RC) is the gold standard treatment for patients with muscle-invasive or refractory non-muscle invasive bladder cancer. It is estimated that approximately 64% and 13% of RC patients experience any complication and major complications, respectively. Specialized immunonutrition (SIM) aims to reduce the rates of complications after RC. We reported surgical complication rates in RC patients who received (SIM group) versus who did not receive (no-SIM group) perioperative SIM. Moreover, we investigated factors associated with complications after RC. MATERIAL AND METHODS: This is a retrospective cohort study of 52 patients who underwent RC between April 2016 and December 2017. Overall, 26 (50%) patients received perioperative SIM. We recorded age, gender, Charlson Comorbidity Index (CCI), body mass index (BMI), Malnutrition Universal Screening Tool (MUST) score, unintentional weight loss (UWL), SIM drinks consume, surgical approach, urinary diversion, neoadjuvant chemotherapy (NAC), use of total parenteral nutrition (TPN), final pathology, length of stay (LOS), and complications. RESULTS: SIM was associated with higher rates of documented infections (P = .03). Conversely, post-operative ileus was associated with higher rates of overall infections (P = .03). Median LOS was comparable within the 2 groups. Overall, 4 (15.38%) versus 0 (0%) patients in SIM versus no-SIM group were readmitted to hospital (P = .03). Age, CCI, NAC, and TPN were not associated with complication rates. CONCLUSIONS: SIM is not associated with lower rates of post-operative complications in RC candidates. Moreover, higher rates of documented infections were observed in the SIM group. Patients with post-operative ileus experienced more infections. Age, CCI, NAC, and TPN were not predictive of complications.

Comparison of Mexican-American vs Caucasian prostate cancer active surveillance candidates.

BACKGROUND: We compared upgrading and upstaging rates in low risk and favorable intermediate risk prostate cancer (CaP) patients according to racial and/or ethnic group: Mexican-Americans and Caucasians. METHODS: Within Surveillance, Epidemiology and End Results database (2010-2015), we identified low risk and favorable intermediate risk CaP patients according to National Comprehensive Cancer Network guidelines. Descriptives and logistic regression models were used. Furthermore, a subgroup analysis was performed to test the association between Mexican-American vs. Caucasian racial and/or ethnic groups and upgrading either to Gleason-Grade Group (GGG II) or to GGG III, IV or V, in low risk or favorable intermediate risk CaP patients, respectively. RESULTS: We identified 673 (2.6%) Mexican-American and 24,959 (97.4%) Caucasian CaP patients. Of those, 14,789 were low risk (434 [2.9%] Mexican-Americans vs. 14,355 [97.1%] Caucasians) and 10,834 were favorable intermediate risk (239 [2.2%] Mexican-Americans vs. 10,604 [97.8%] Caucasians). In low risk CaP patients, Mexican-American vs. Caucasian racial and/or ethnic group did not result in either upgrading or upstaging differences. However, in favorable intermediate risk CaP patients, upgrading rate was higher in Mexican-Americans than in Caucasians (31.4 vs. 25.5%, OR 1.33, P = 0.044), but no difference was recorded for upstaging. When comparisons focused on upgrading to GGG III, IV or V, higher rate was recorded in Mexican-American relative to Caucasian favorable intermediate risk CaP patients (20.4 vs. 15.4%, OR 1.41, P = 0.034). CONCLUSION: Low risk Mexican-American CaP patients do not differ from low risk Caucasian CaP patients. However, favorable intermediate risk Mexican-American CaP patients exhibit higher rates of upgrading than their Caucasian counterparts. This information should be considered at treatment decision making.

Modified-BEP Chemotherapy in Patients With Germ-Cell Tumors Treated at a Comprehensive Cancer Center.

OBJECTIVES: Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain patients. In an attempt to reduce bleomycin-toxicity, we developed a modified-BEP (mBEP) regimen. MATERIALS AND METHODS: Between August 2008 and February 2018, 182 unselected mainly testicular GCT patients (39 with adjuvant purpose and 143 with curative purpose) received a tri-weekly 5-day hospitalization schedule with bleomycin 15 U intravenous (IV) push on day 1 and 10 U IV continuous infusion over 12 hours on days 1 to 3, cisplatin 20 mg/m IV, and etoposide 100 mg/m IV on days 1 to 5. Pulmonary toxicity was assessed through chest computed tomography scan and clinical monitoring. RESULTS: Median number of mBEP cycles was 3 (range: 1 to 4). In the curative setting, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic system, 112, 21, and 9 patients had good-risk, intermediate-risk, and poor-risk class, respectively; 66 (46%) patients had complete response (CR), 67 (47%) had partial response (52 of whom became CR afterwards), 6 (4%) had stable disease (that in 3 became CR afterwards), 3 (2%) progressed, and 1 (1%) died of brain stroke. At a median follow-up of 2.67 years (interquartile range: 1.23-5.00 y), 1 and 5-year overall survival and progression-free survival were 99% and 95%, and 90% and 88%, respectively. In the entire patient population, there was grade 3/4 neutropenia in 92 patients (51%), febrile neutropenia in 11 patients (6%), grade 1/2 nausea in 74 patients (41%), and no death due to pulmonary toxicity. CONCLUSION: In GCT patients, our mBEP-schedule would suggest an effective treatment modality without suffering meaningful pulmonary toxicity.

Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer.

BACKGROUND: Despite adjuvant intravesical therapy, recurrences in non-muscle-invasive bladder cancer (NMIBC) are still high; therefore, new treatment options are needed. The use of chemohyperthermia (CHT) as an alternative treatment is expanding in Europe. To date, however, there has been a lack of prospective randomised data. OBJECTIVE: To compare CHT using mitomycin C (MMC) with bacillus Calmette-Guérin (BCG) as adjuvant treatment for intermediate- and high-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 2002 and 2012, 190 NMIBC patients were randomised in this controlled, open-label, multicentre trial for 1-yr CHT (six weekly treatments and six maintenance treatments) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment. This study is registered with ClinicalTrials.gov (NCT00384891). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was 24-mo recurrence-free survival (RFS) in the intention-to-treat (ITT) and per-protocol (PP) analyses in all papillary NMIBC patients (n=147). Analyses were done with the log-rank test and Fisher exact test. All tests were two-sided. RESULTS AND LIMITATIONS: The 24-mo ITT RFS was 78.1% in the CHT group compared with 64.8% in the BCG group (p=0.08). The 24-mo RFS in the PP analysis was 81.8% in the CHT group compared with 64.8% in the BCG group (p=0.02). Progression rates were <2% in both groups. Regarding the side-effects, no new safety concerns were identified. A concern is that this study closed prematurely and thus is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias. CONCLUSIONS: CHT is a safe and effective treatment option in patients with intermediate- and high-risk papillary NMIBC. A significantly higher 24-mo RFS in the CHT group was seen in the PP analysis. Based on the results above, CHT is an option for BCG therapy as adjuvant treatment for intermediate- and high-risk papillary NMIBC. PATIENT SUMMARY: Recurrences in non-muscle-invasive bladder cancer are common, despite adjuvant therapies. We compared 24-mo recurrence-free survival (RFS) with chemohyperthermia (CHT) versus bacillus Calmette-Guérin (BCG) therapy. According to these data, CHT therapy appears to be safe and has higher 24-mo RFS than BCG therapy.

Is there still a role for sorafenib in metastatic renal cell carcinoma? A systematic review and meta-analysis of the effectiveness of sorafenib over other targeted agents.

BACKGROUND: The treatment of metastatic renal cell carcinoma (mRCC) has largely improved over the last decade, due to the availability of several targeted agents (TAs). Sorafenib was the first TA to report a benefit in terms of PFS in this disease, and it has largely been used as a comparator in randomized trials. We tested its activity compared to other TAs by performing a systematic review and meta-analysis. METHODS: MEDLINE/PubMed, the Cochrane library, and the ASCO university websites were searched for randomized phase II or III trials that compared other TAs to sorafenib in mRCC. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The measured outcomes were progression free survival (PFS), overall survival (OS), and the overall response rate (ORR). Sub-analyses were performed for MSKCC prognostic groups and lines of therapy. RESULTS: A total of 3094 patients were evaluable for PFS. Other TAs significantly reduce the risk of progression compared to sorafenib (HR=0.78; 95% CI, 0.72-0.85; p<0.001). This difference remains significant in patients in a good prognostic group with respect to both first- (HR=0.61; 95%CI, 0.44-0.85; p=0.003) and second-line therapy (HR=0.58; 95% CI, 0.42-0.79; p<0.001). No significant differences were, however, found in patients with an intermediate prognosis in terms of both first- (HR=0.80; 95% CI, 0.60-1.00; p=0.05) and second-line treatment (HR=0.89; 95% CI, 0.73-1.07; p=0.21). In 2922 patients evaluable for OS, no significant difference was found between other TAs and sorafenib (HR=1.07; 95% CI, 0.97-1.18; p=0.18). A benefit was also not identified when the analysis was limited to patients treated with first or subsequent lines of therapy or in patients previously treated with sunitinib. Significant differences were found in terms of the ORR in the 2963 evaluable patients favoring other TAs (RR=1.48; 95% CI, 1.24-1.76; p<0.001). This difference remain significant when a sub-analysis was performed per line of therapy. CONCLUSIONS: Other TAs improve PFS but not OS when compared to sorafenib. The use of sorafenib in patients with an intermediate prognosis, especially in second-line therapy, does not have a detrimental effect on PFS and might be an option for certain patients.

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®).

BACKGROUND: Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. METHODS: 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. RESULTS: Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. CONCLUSIONS: Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. TRIAL REGISTRATION: NCT02130713. Date of trial Registration: 30/04/2014.