Search

BackgroundIn the PURE-01 study (NCT02736266), we aimed to evaluate the ability to predict the pathologic complete response (pT0N0) after pembrolizumab by using clinical and tumor biomarkers.MethodsIn an open-label, single-arm, phase 2 study, 3 courses of 200 mg pembrolizumab preceding radical cystectomy were administered in patients with T2-4aN0M0 muscle-invasive bladder cancer. The analyses included a comprehensive genomic profiling and programmed cell-death-ligand-1 (PD-L1)–combined positive score assessment (CPS; Dako 22C3 antibody) of pre- and posttherapy samples. Multivariable logistic regression analyses evaluated baseline clinical T stage and tumor biomarkers in association with pT0N0 response. Corresponding coefficients were used to develop a calculator of pT0N0 response based on the tumor mutational burden (TMB), CPS, and the clinical T stage. Decision-curve analysis was also performed. All statistical tests were 2-sided.ResultsFrom February 2017 to June 2019, 112 patients with biomarker data were enrolled (105 with complete TMB and CPS data). Increasing TMB and CPS values featured a linear association with logistic pT0N0 probabilities (P = .02 and P = .004, respectively). For low TMB values (≤11 mut/Mb, median value, n = 53), pT0N0 probability was not associated with increasing CPS. Conversely, for high TMB values (>11 mut/Mb, n = 52), pT0N0 was statistically significantly associated with higher CPS (P = .004). The C index of the pT0N0 probability calculator was 0.77. On decision-curve analysis, the net benefit of the model was higher than the “treat-all” option within the clinically meaningful threshold probabilities of 40%-50%.ConclusionsThe study presents a composite biomarker-based pT0N0 probability calculator that reveals the complex interplay between TMB and CPS, added to the clinical T stage.

Background and Aims The use of Pembrolizumab, a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 receptor, has been largely accepted, especially in a series of trials in patients with advanced melanoma and in other cancers such as renal cell carcinoma (RCC), lymphoma and others. However, few recent studies demonstrated that Pembrolizumab promotes several renal dysfuncion such as acute tubular injury, acute interstitial nephritis and minimal change disease. To better elucidate this topic, we analyzed the renal function’s aspects from the PURE-01 protocol’s data, a phase 2, open label study of neoadjuvant Pembrolizumab before radical cystectomy (RC) for muscle invasive urothelial bladder cancer (MIUB). Method PURE-01 study (NCT02736266) enrolled preliminary 143 patients (pts). Eligibility criteria included: T2-T4N0 stage and residual disease after transurethral reduction of bladder. Pts received 3 cycles of Pembrolizumab 200 mg 3 weekly before RC. Computed tomography scan, FDG-PET/CT scan, and bladder multipara metric magnetic resonance imaging were performed during screening and before RC. Radiologically non-responders to pembro (per investigator decision) are given 3 additional courses of dose-dense MVAC chemotherapy. The collected data consisted in: the serum creatinine at baseline, after the first, second and last cycle in order to obtain the renal function by using eGFR formula (CKD-EPI-2009) for each time step; urine test analysis data after each cycle; the T stage from cTNM (AJCC TNM system-2019) before the treatment; clinical data such as presence of Diabetes, Hypertension, Hydronephrosis, BMI. The main outcome of the study was to correlate the renal function variation (from the pre-treatment to each treatment cycle) with the other clinical variables. Data analysis were performed using linear model, Kruskal-Wallis test and Wilcoxon test with holm’s correction. Results The median age of the patients was 68 years (62-73), with the 13% of the pts as female. We observed the presence of Hypertension, Hydronephrosis, Diabetes, Overweight (BMI≥25 and BMI Conclusion We observed that the treatment with neoadjuvant pembrolizumab, in patients with bladder cancer, does not correlate with a decay of eGFR, but on the contrary, from our data, is associated with a small improvement of renal function, especially for those patients who presented higher stage of T and hydronephrosis before the treatment suggesting the Permbrolizumab’s safety in neoadjuvant therapy before RC for MIUBC from the nephrological point of view. This results needs more in-depths studies to be confirmed.

Introduction Extended pelvic lymph node dissection (ePLND) might be associated with damages to the pelvic plexus, potentially affecting erectile function (EF) recovery after radical prostatectomy (RP). However, the impact of the extent of pelvic lymph node dissection (PLND) on EF has never been addressed. Aim The aim of this study is to evaluate the impact of ePLND on potency recovery in patients who underwent bilateral nerve‐sparing RP (BNSRP). Methods The study included 396 patients with prostate cancer treated with BNSRP by two high‐volume surgeons. Patients were retrospectively divided into two groups based on PLND status: no PLND (N = 161; 40.9%) and ePLND (N = 235; 59.1%) at the time of BNSRP. All patients had preoperative functional and oncological data. Univariable and multivariable Cox regression models tested the association between ePLND and EF recovery after surgery, after accounting for confounders. Main Outcome Measure The International Index of Erectile Function (IIEF) was used to evaluate EF after BNSRP. Postoperative EF recovery was defined as an IIEF‐EF domain score ≥22. Results At a mean follow up of 33.2 months after surgery (median 30), 183 patients (46.2%) recovered EF. Overall, postoperative EF recovery rate at 2 years was 48.4%. No significant differences were recorded when patients were stratified according to the extent of PLND (EF recovery rates at 2‐year: 46.6% vs. 49.7% for patients who did not undergo PLND vs. those treated with ePLND; P = 0.33). These results were confirmed at multivariable analyses, where only age at surgery and preoperative IIEF‐EF (all P ≤ 0.03), but not ePLND ( P = 0.8), represented independent predictors of EF recovery. Conclusions The extent of PLND is not associated with potency after BNSRP. Conversely, other factors such as age at surgery and preoperative EF represent the major predictors of postoperative potency recovery. Therefore, when indicated, ePLND can be safely performed without compromising EF outcomes. Gandaglia G, Suardi N, Gallina A, Abdollah F, Capitanio U, Salonia A, Colombo R, Bianchi M, Chun FK, Hansen J, Rigatti P, Montorsi F, and Briganti A. Extended pelvic lymph node dissection does not affect erectile function recovery in patients treated with bilateral nerve‐sparing radical prostatectomy. J Sex Med 2012;9:2187–2194.

Introduction. Several studies have shown that erectile function (EF) recovery in patients undergoing bilateral nerve sparing radical prostatectomy (BNSRP) improves significantly when phosphodiesterase type 5 inhibitors (PDE5) are administered following surgery. Methods. We included 293 patients treated with BNSRRP at a single center. Postoperative EF recovery was defined as an EF domain score of the International Index of Erectile Function (IIEF) >= 22. No patient received any treatment for postoperative erectile dysfunction (ED). Kaplan-Meier curves assessed time to EF recovery according to patient age, preoperative EF, and Charlson comorbidity index (CCI). Univariable and multivariable Cox regression models tested the association between predictors and EF recovery. Finally, the rate of EF recovery of untreated patients after BNSRP was compared with a subset of patients with similar preoperative characteristics but receiving PDE5. Main Outcome Measure. The main outcome measure of this article was the IIEF-EF domain score. Results. Overall, 105/293 (35.8%) reached an IIEF-EF >= 22 after a mean follow-up of 26.8 months. At multivariable analyses, age, preoperative IIEF-EF, and CCI achieved independent predictor status (all P 70 years (P < 0.001). Similarly, preoperatively fully potent patients (IIEF-EF >= 26) had a 56.6% chance of recovering EF after surgery compared with 18% of patients with severe ED before surgery (P < 0.001). The rate of EF recovery in untreated patients < 55 years and with a pre-op IIEF-EF >= 22 was higher but did not differ significantly from comparable patients receiving PDE5 (P = 0.11). Conclusions. Overall, the rate of EF postoperative recovery in patients left untreated after surgery is modest (35.8%). Although younger patients with a good preoperative EF may experience good EF recovery rates even without any treatment, use of PDE5 after surgery further improved their functional outcomes. Therefore, a therapy for ED should be offered to all patients treated with BNSRP. Gallina A, Ferrari M, Suardi N, Capitanio U, Abdollah F, Tutolo M, Bianchi M, Sacca A, Salonia A, Rigatti P, Montorsi F, and Briganti A. Erectile function outcome after bilateral nerve sparing radical prostatectomy: Which patients may be left untreated? J Sex Med 2012; 9: 903-908. Introduction. Several studies have shown that erectile function (EF) recovery in patients undergoing bilateral nerve sparing radical prostatectomy (BNSRP) improves significantly when phosphodiesterase type 5 inhibitors (PDE5) are administered following surgery. Methods. We included 293 patients treated with BNSRRP at a single center. Postoperative EF recovery was defined as an EF domain score of the International Index of Erectile Function (IIEF) >= 22. No patient received any treatment for postoperative erectile dysfunction (ED). Kaplan-Meier curves assessed time to EF recovery according to patient age, preoperative EF, and Charlson comorbidity index (CCI). Univariable and multivariable Cox regression models tested the association between predictors and EF recovery. Finally, the rate of EF recovery of untreated patients after BNSRP was compared with a subset of patients with similar preoperative characteristics but receiving PDE5. Main Outcome Measure. The main outcome measure of this article was the IIEF-EF domain score. Results. Overall, 105/293 (35.8%) reached an IIEF-EF >= 22 after a mean follow-up of 26.8 months. At multivariable analyses, age, preoperative IIEF-EF, and CCI achieved independent predictor status (all P 70 years (P < 0.001). Similarly, preoperatively fully potent patients (IIEF-EF >= 26) had a 56.6% chance of recovering EF after surgery compared with 18% of patients with severe ED before surgery (P < 0.001). The rate of EF recovery in untreated patients < 55 years and with a pre-op IIEF-EF >= 22 was higher but did not differ significantly from comparable patients receiving PDE5 (P = 0.11). Conclusions. Overall, the rate of EF postoperative recovery in patients left untreated after surgery is modest (35.8%). Although younger patients with a good preoperative EF may experience good EF recovery rates even without any treatment, use of PDE5 after surgery further improved their functional outcomes. Therefore, a therapy for ED should be offered to all patients treated with BNSRP. Gallina A, Ferrari M, Suardi N, Capitanio U, Abdollah F, Tutolo M, Bianchi M, Sacca A, Salonia A, Rigatti P, Montorsi F, and Briganti A. Erectile function outcome after bilateral nerve sparing radical prostatectomy: Which patients may be left untreated? J Sex Med 2012; 9: 903-908.

BACKGROUND It would be of value to identify ongoing spermatogenesis molecular markers which can predict successful sperm recovery in patients with non-obstructive azoospermia undergoing conventional or microsurgical testicular sperm extraction (TESE/microTESE). ESX1 is an X-linked homeobox gene expressed in testis, placenta, brain and lung in humans and specifically in pre- and post-meiotic germ cells of the testis in mice. METHODS We investigated the sequence, expression (by RT-PCR) and epigenetic status (by promoter pyrosequencing) of ESX1 in testicular tissue samples, obtained from 81 azoospermic subjects in the context of surgical sperm extraction, to check a possible association between ESX1 alterations and impaired spermatogenesis, as determined by histological analysis. RESULTS The ESX1 transcript was detected in 100% of cases diagnosed as obstructive azoospermia (33), hypospermatogenesis (18) and incomplete maturation arrest (MA) (2), and sperm recovery was also successful in 100% of these cases. ESX1 mRNA was also detected in 5 of 6 patients with incomplete Sertoli cell-only syndrome, in 4 of 6 subjects with complete MA but in only 3 of 16 cases of complete Sertoli cell-only syndrome (cSCOS), whereas sperm recovery was successful in 4 of 6, 2 of 6 and 5 of 16 of these patients, respectively. In cases of focal spermatogenesis, ESX1 expression and sperm retrieval were concordant in 14 of 19 (74%) cases subjected to TESE, but in only 3 of 11 (27%) men who underwent microTESE. With TESE, but not with microTESE, both samples originated from adjacent testicular areas. The pyrosequencing of the ESX1 CpG island revealed methylation levels that were significantly lower in ESX1 expressors when compared with non-expressors. CONCLUSIONS ESX1 emerges as a potentially reliable spermatogenesis molecular marker, whose clinical value as a predictor of successful sperm retrieval warrants further studies.

Introduction Selective serotonin reuptake inhibitors are the most widely used agents for delaying ejaculation in patients with premature ejaculation (PE). Aim The aim of this study was to assess the acceptance of and the discontinuation rate from paroxetine treatment in patients with lifelong PE. Methods We analyzed the acceptance of and discontinuation rates of 93 consecutive potent patients (mean age, 37.6 years) seeking medical treatment for lifelong PE. The patients were assessed with detailed medical and sexual history, self-reported intravaginal ejaculatory latency time, self-administered International Index of Erectile Function, complete physical examination, and the Meares–Stamey test. The patients received a paroxetine prescription (10 mg daily for 21 days and then 20 mg as needed) for the first 3 months. Thereafter, the patients could either stay with the same on-demand treatment or take paroxetine 10 mg daily for 3 months. The patients were evaluated at 3 and 6 months, and requested to complete multiple-choice global assessment questions regarding specific reasons for eventual therapy discontinuation. Main Outcome Measures The primary end point was acceptance and discontinuation rates for paroxetine treatment in patients seeking medical treatment for lifelong PE. The secondary end point was the reasons for nonacceptance of treatment or discontinuation. Results Twenty-eight (30.10%) patients decided not to start paroxetine. Fear of using an “antidepressant drug” was the main reason (42.9%) for treatment nonacceptance. Twenty (30.8%) patients who initiated therapy eventually discontinued it. Treatment effect below expectations was the main reason of treatment dropout (75%) during the first 3 months, followed by temporary loss of interest in sex because of relationship issues (15%) and side effects (10%). Of the patients who continued treatment, 77.8% preferred daily paroxetine, while 22.2% continued as-needed therapy. Conclusions Thirty percent of lifelong PE patients seeking medical treatment for complaints of early ejaculation freely decided not to start any paroxetine treatment, and roughly 30% of patients who started therapy eventually discontinued it. Salonia A, Rocchini L, Sacca A, Pellucchi F, Ferrari M, Del Carro U, Ribotto P, Gallina A, Zanni G, Deho' F, Rigatti P, and Montorsi F. Acceptance of and discontinuation rate from paroxetine treatment in patients with lifelong premature ejaculation. J Sex Med 2009;6:2868–2877.

Introduction Only few reports addressed the outcome of patients submitted to anatomical radical retropubic prostatectomy (RRP) with an indwelling inflatable penile prosthesis (IPP). Aim To assess the feasibility and safety of RRP in patients with clinically localized prostate cancer and a previously implanted with an IPP. Main Outcome Measures We evaluated the surgical parameters and the follow-up functional results in this particular patient population. Methods Four patients previously submitted to IPP implant for severe erectile dysfunction underwent RRP for organ-confined prostate cancer. Patients' charts were carefully reviewed to investigate pre- and perioperative details. Patients were evaluated by the International Index of Erectile Function (IIEF) preoperatively and at 6 months postoperatively. Patients were then contacted to assess long-term functional and oncological outcome. Results The outcome of the procedures was comparable to a normal population in terms of operating time, estimated blood loss, hospitalization time, and pathological outcome. No injury to the preexisting penile implant was reported. Continence was obtained in 3 (75%) patients at catheter removal, and in 1 (25%) patient at the 1-month follow-up. No major intra- and postoperative complications were reported. All patients were able to use their prosthesis after RRP. No statistical difference in pre- and post-RRP EF domain scores was found. Conclusion The presence of an IPP in patients with prostate cancer is not a contraindication to perform an anatomical RRP. Surgery can be performed safely without injuring the implant and the clinical outcome in these patients is satisfactory. Postoperative implant use is not affected by RRP. Deho' F, Salonia A, Briganti A, Zanni G, Gallina A, Rokkas K, Guazzoni G, Rigatti P, and Montorsi F. Anatomical radical retropubic prostatectomy in patients with a preexisting three-piece inflatable prosthesis: A series of case reports. J Sex Med 2009;6:578–583.