Purpose: The PURE-01 study (NCT02736266) pioneered the neoadjuvant immune-checkpoint inhibitor (ICI) therapy before radical cystectomy (RC) in patients with muscle-invasive urothelial bladder carcinoma (MIBC). We herein present the survival outcomes after a median follow-up of three years. Patients and Methods: The intention-to-treat (ITT) population included 155 patients. Event-free survival (EFS) was defined as the time from pembrolizumab initiation until radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy, recurrence after RC, or death. Further outcomes were recurrence-free survival (RFS) post-RC and overall survival (OS). Multivariable Cox regression analyses for EFS were performed. Kaplan–Meier analyses compared EFS outcomes according with baseline programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS) and according to the molecular subtypes. Results: After a median (interquartile range, IQR) follow-up of 39 (30–47) months, 36-month EFS and OS were 74.4% [95% confidence interval (CI), 67.8–81.7] and 83.8% (95% CI, 77.8–90.2) in the ITT population, respectively. Overall, 143 (92.3%) patients underwent RC. Within the cohort of patients who did not receive additional chemotherapy (N = 125), 36-month RFS was 96.3% (95% CI, 91.6–100) for patients achieving a ypT0N0, 96.1% (95% CI, 89–100) for ypT1/a/isN0, 74.9% (95% CI, 60.2–93) for ypT2–4N0, and 58.3% (95% CI, 36.2–94.1) for ypTanyN1–3 response. EFS was significantly stratified among PD-L1 tertiles (lower tertile: 59.7% vs. medium tertile: 76.7% vs. higher tertile: 89.8%, P = 0.0013). The claudin-low and basal/squamous subtypes displayed the lowest rates of events. Conclusions: At a median follow-up of three years, PURE-01 results further confirm the sustained efficacy of neoadjuvant pembrolizumab before RC. PD-L1 expression was the strongest predictor of sustained response post-RC.

Radical prostatectomy has progressively become an elective treatment for primary localized prostate cancer as well as for incidental or subsequent prostatic cancer after previous surgery for obstructive benign disease. This increased acceptance opens concerns about oncological and functional outcomes. Between July 1999 and August 2003, 109 patients underwent radical retropubic prostatectomy for prostate cancer as a second line approach after surgery for primary bladder outlet obstruction. Of these patients 88 had undergone previous transurethral resection of the prostate and 21 had undergone open prostatectomy. Incidental and delayed prostate cancer was detected in 71 and 38 cases, respectively. Perioperative and postoperative morbidity was evaluated in all patients, while postoperative functional outcomes were assessed by a subjective questionnaire in 43. As a second surgery, radical retropubic prostatectomy was generally more complex technically and it resulted in longer operative time compared to radical surgery in naïve patients. In contrast, early and delayed postoperative morbidity increased moderately. Complete urinary continence was documented in 32 (74%) and 37 patients (86%) at the 6 and 12-month follow-ups, respectively. In this patient cohort adequate erectile function was reported by 12%. Radical retropubic prostatectomy can be performed safely after previous prostate surgery for bladder outlet obstruction. However, a consistent surgical background in prostate surgery is needed to manage frequently unexpected difficulties. Candidates for second line prostate surgery should be informed that functional results are less predictable and satisfactory than those achieved after the same surgical approach in naïve patients.

We assessed postoperative clinical outcomes such as day and nighttime urinary continence and overall sexual function in patients who underwent nerve and seminal sparing cystectomy with ileocapsuloplasty compared with patients after standard cystoprostatectomy with similar orthotopic urinary reservoir. A total of 27 patients (mean age 52 years, range 36 to 61) with superficial high risk or muscular invasive T2 bladder cancer underwent radical nerve and seminal sparing cystectomy with ileocapsule anastomosis. Postoperative clinical outcomes such as urinary continence, voiding patterns and urodynamic parameters were evaluated at 3, 6 and 12 months, while overall sexual function was determined at baseline and at 6 and 12-month followup. Nerve and seminal sparing cystectomy provides better outcomes in terms of urinary and urodynamic parameters compared to standard cystoprostatectomy. Furthermore, fully normal postoperative erectile function and satisfactory overall sexual quality of life were documented at early and delayed followup in all patients. A retrograde ejaculation with reliable sperm retrieval from urine was also documented. Although these findings need to be confirmed in a larger patient population, when respecting rigorous patient selection criteria and careful postoperative surveillance, nerve and seminal sparing cystectomy seems to offer satisfactory clinical and functional outcomes. From an oncological point of view, long-term followup is of paramount importance to confirm whether this surgical procedure can be proposed as a valid choice of treatment for young, fully potent and socially active patients with organ confined bladder cancer.

We compared the efficacy of paroxetine alone and combined with sildenafil in patients complaining of premature ejaculation. Enrolled in this study were 80 consecutive potent men 19 to 47 years old (mean age 34) with premature ejaculation but without any obvious organic cause. Pretreatment evaluation included a history, self-administration of the International Index of Erectile Function (IIEF) questionnaire, physical examination and the Meares-Stamey test to exclude genital tract infection. The initial 40 patients received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed, that is 3 to 4 hours before planned sexual activity, for 6 months (group 1). The other group of 40 men received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed plus 50 mg. sildenafil as needed, that is 1 hour before planned sexual activity, for 6 months (group 2). Patients were followed 3 and 6 months after beginning therapy and were evaluated using several general assessment questions, IIEF and ejaculatory latency time. Mean ejaculatory latency time +/- SE in group 1 was 0.33 +/- 0.04, 3.7 +/- 0.10 (p <0.01) and 4.2 +/- 0.03 (p <0.01) minutes at baseline, 3 and 6-month followup, while in group 2 it was 0.35 +/- 0.03, 4.5 +/- 0.07 (p <0.01) and 5.3 +/- 0.02 (p <0.001) minutes, respectively. When improvement in ejaculatory latency time was compared in the 2 groups, group 2 results proved to be significantly greater (p <0.05). Baseline, and 3 and 6-month mean intercourse satisfaction domain values of the IIEF were 9, 11 and 11 (p = 0.09, not significant), and 9, 11 and 14 (p <0.05) in groups 1 and 2, respectively. Group 2 patients reported significantly greater intercourse satisfaction than those in group 1 (p <0.05). At baseline, 3 and 6 months there was a mean of 0.9 +/- 0.1, 1.7 +/- 0.3 (not significant) and 2.5 +/- 0.3 (p <0.01) coitus episodes weekly in group 1, and 1 +/- 0.2, 2.3 +/- 0.3 (p <0.01) and 3.2 +/- 0.1 (p <0.001) in group 2, respectively. Group 2 patients reported a significantly higher number of coitus episodes weekly (p <0.05). Side effects in the 40 group 1 cases included anejaculation in 1 (2.5%), gastrointestinal upset and/or nausea in 5 (12.5%), headache in 4 (10%) and decreased libido in 2 (5%). Side effects in the 40 group 2 cases included anejaculation in 1 (2.5%), headache in 8 (20%), gastrointestinal upset and/or nausea in 6 (15%) and flushing in 6 (15%). Group 2 patients reported significantly more headaches (p <0.01) and flushing episodes (p <0.001) than those in group 1. After 6 months of treatment 33 men (82.5%) in group 1 and 36 (90%) in group 2 were willing to continue therapy (not significant). Paroxetine combined with sildenafil appears to provide significantly better results in terms of ejaculatory latency time and intercourse satisfaction versus paroxetine alone in potent patients with premature ejaculation. However, combined treatment is associated with a mild increase in drug related side effects.