Therapeutic vaccines and immune checkpoints inhibition options for gynecological cancers.

Treatments for gynecological cancer include surgery, chemotherapy, and radiation. However, overall survival is not improved, and novel approaches are needed. Immunotherapy has been proven efficacious in various types of cancers and multiple approaches have been recently developed. Since numerous gynecological cancers are associated to human papilloma virus (HPV) infections, therapeutic vaccines, targeting HPV epitopes, have been developed. The advancing understanding of the immune system, regulatory pathways and tumor microenvironment have produced a major interest in immune checkpoint blockade, Indeed, immune checkpoint molecules are important clinical targets in a wide variety of tumors, including gynecological. In this review, we will describe the immunotherapeutic targets and modalities available and review the most recent immunotherapeutic clinical trials in the context of gynecological cancers. The synergic results obtained from the combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, or immune checkpoint inhibitors, may underlie the potential for a novel therapeutic scenario for these tumors.

Vaginal Native Tissue Repair for Posterior Compartment Prolapse: Long-Term Analysis of Sexual Function and Quality of Life in 151 Patients.

OBJECTIVES: The aim of this study was to assess the effectiveness and safety of vaginal native tissue repair for symptomatic rectocele and to evaluate the impact on quality of life (QoL) and sexual function. METHODS: One hundred fifty-one patients affected by rectocele stage II or higher according to the Pelvic Organ Prolapse Quantification System were enrolled. Patients underwent vaginal native tissue repair. Postoperative assessments consisted in a clinical examination and assessment of posterior compartment symptoms and defecatory dysfunctions. These were conducted 1, 12, and 60 months after surgery. Patients completed the Prolapse Quality-of-Life questionnaire, the Pelvic Floor Disability Index, the Pelvic Floor Impact Questionnaire, and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form. RESULTS: The median follow-up was 64 (60-72) months. The median operative time was 55 (37-127) minutes, and the median postoperative hospital stay was 2 (2-4) days. No intraoperative complications occurred. At median follow-up, an objective cure rate of 88.2% was observed. Seventeen patients (11.3%) showed recurrent posterior vaginal descent stage II or higher. Defecatory dysfunctions, vaginal digitation, and vaginal bulge decreased significantly. The change of values of the Prolapse Quality-of-Life, Pelvic Floor Disability Index, and Pelvic Floor Impact Questionnaire questionnaires has shown a significant improvement in the QoL after surgery. The percentage of patients regularly practicing sexual activity increased, and dyspareunia decreased after treatment. CONCLUSIONS: Vaginal native tissue repair is a safe and effective procedure for symptomatic rectocele, with a low rate of complications, and improves pelvic organ prolapse-related symptoms, QoL, and sexual function.

Prevention of recurrent lower urinary tract infections in postmenopausal women with genitourinary syndrome: outcome after 6 months of treatment with ospemifene.

Aim of this study was to evaluate the efficacy of ospemifene in the prevention of recurrent lower urinary tract infections in postmenopausal women with vulvovaginal atrophy. The study have a retrospective design. Thirty-nine patients were enrolled. Patients underwent clinical examination and urine culture. The urinary symptoms and the quality of life were evaluated with UTISA score, PUF and SF-36 questionnaires before and after treatment. All 39 patients received ospemifene 60 mg one tablet/daily for 6 months. Adverse effects and complications were assessed. Thirty-nine patients were enrolled in the study. Two patients experienced one new UTI episode and the mean number of positive urine culture decreased significantly after 6 months (3.65 ± 2.12 vs 0.25 ± 0.17, p < .0001). The mean number of urinary infection symptoms decreased significantly after treatment; dysuria reduced (4.76 ± 2.45 vs 0.89 ± 1.12). PUF score and SF-36 showed a statistically significant change (22.43 ± 5.89 vs 12.14 ± 3.21) and (52.86 ± 9.21 vs 83.43 ± 10.76). No adverse effects were reported and the total success rate was the 92.3% after 6 months at PGI-I. Ospemifene is a valid alternative with excellent tolerability for the UTIS prevention in postmenopausal patients.

Efficacy and tolerability of treatment with mirabegron compared with solifenacin in the management of overactive bladder syndrome: A retrospective analysis.

AIM: The aim of this study was to compare the efficacy and tolerability of solifenacin and mirabegron in patients with overactive bladder (OAB) syndrome. METHODS: We carried out a retrospective analysis in 342 women affected by OAB syndrome; 168 were treated with solifenacin 5 mg/daily and 174 with mirabegron 50 mg/daily. A clinical evaluation, 3-day voiding diary, and urodynamic testing was performed. Patients completed the Overactive Bladder Questionnaire - Short Form, the King's Health Questionnaire, and the Patient Global Impression of Improvement questionnaire. The adverse effects were evaluated. The two groups were compared at baseline and at 12 weeks. RESULTS: After 12 weeks, a significant reduction in the mean number/24 h of voids and urgent micturition episodes/24 h was observed in both groups. Detrusor overactivity decreased from 58.3% to 13.1% in the solifenacin group and from 58% to 11% in the mirabegron group. Twenty (12%) and 18 (10.7%) patients taking solifenacin reported constipation and dry mouth, respectively, versus four (2.3%) and five (2.9%) patients taking mirabegron, respectively, but there was no difference between the groups in the change in vital signs. The Overactive Bladder Questionnaire - Short Form and King's Health Questionnaire scores did not demonstrate significant differences and the abandonment rates in the solifenacin and mirabegron groups were 25.5% and 20%, respectively. CONCLUSION: Solifenacin and mirabegron showed the same efficacy in the treatment of OAB but solifenacin had more adverse effects.

Retrospective analysis in 46 women with vulvovaginal atrophy treated with ospemifene for 12 weeks: improvement in overactive bladder symptoms.

AIMS: The aim of this study was to assess the effectiveness and safety of ospemifene in the improvement of overactive bladder (OAB) symptoms in postmenopausal women affected by vulvovaginal atrophy (VVA). METHODS: Forty-six postmenopausal patients affected by VVA with OAB syndrome were enrolled for the study. All patients received Ospemifene 60 mg for 12 weeks. Clinical examination, 3-day voiding diary, urodynamic testing, ultrasound measurement of endometrial and bladder wall thickness (BWT) and the Vaginal Health Index (VHI) were performed at baseline and 12 weeks. Patients completed the OAB-Q SF and UDI-6. RESULTS: After 12-weeks, the number of patients with detrusor overactivity decreased from 39% to 13% (p = 0.04). The reduction in the mean number in 24 h of voids (9.57 ± 2.12 vs. 6.63 ± 1.22, p < 0.0001), urgent micturition episodes/24 h (5.63 ± 1.46 vs. 1.44 ± 1.31, p < 0.0001), nocturia episodes (3.17 ± 0.85 vs. 1.11 ± 1.18, p < 0.0001), urinary incontinence episodes/24 h (0.85 ± 0.96 vs. 0.33 ± 0.64, p = 0.003) was observed. The UDI-6, OAB-Q symptoms, OAB-Q (HRQL) scores were 8.95 ± 0.91 vs. 5.56 ± 1.40, 62.60 ± 14.70 vs. 20.08 ± 10.83 and 18.71 ± 7.41 vs. 79.45 ± 14.47 (p < 0.001) before and after 12 weeks. CONCLUSION: Ospemifene is an effective potential therapy for postmenopausal women with VVA improving OAB symptoms and quality of life.