Intracavernous Injections of Bone Marrow Mononucleated Cells for Postradical Prostatectomy Erectile Dysfunction: Final Results of the INSTIN Clinical Trial.

We recently reported stage I of a phase 1/2 clinical trial of cell therapy to treat postradical prostatectomy erectile dysfunction (INSTIN, INtra-cavernous STem-cell INjection clinical trial, NCT01089387). In this first stage, four doses of intracavernous autologous bone marrow mononuclear cells (BM-MNCs) were tested in 12 patients. Here, we report the results of stage II, in which six additional patients received the optimal dose identified in stage I (109 BM-MNCs), and the long-term results in the 12 patients included in stage I. The objectives were to assess the safety and efficacy of this new treatment. In stage II, no patients had side effects, and the erectile function improvements were similar to those seen in stage I: after 6 months, significant improvements versus baseline were noted in International Index of Erectile Function-15 intercourse satisfaction (7.8±3.1 vs 2.2±3.4, p=0.033) and erectile function (18±8.3 vs 3.7±4.1, p=0.035) domains. In stage I patients, after a mean follow-up of 62.1±11.7 mo, there were no prostate cancer recurrences, and erectile function scores were somewhat lower compared with the 1-yr time point. These findings suggest that intracavernous BM-MNC injections are safe and improve erectile function. The decline in erectile function over time suggests a need for assessing repeated injections. PATIENT SUMMARY: We report a phase 1/2 pilot clinical trial of cell therapy consisting in intracavernous injection of bone marrow mononuclear cells to treat postradical prostatectomy erectile dysfunction. Erectile function was improved after 6 mo in the patients given 1×109 cells. No serious side effects (life threatening or requiring hospitalisation) occurred after a mean follow-up of 62.1 mo in the first 12 patients.

Safety of Intracavernous Bone Marrow-Mononuclear Cells for Postradical Prostatectomy Erectile Dysfunction: An Open Dose-Escalation Pilot Study.

UNLABELLED: Evidence from animal models replicating postradical prostatectomy erectile dysfunction (pRP-ED) suggests intracavernous injection of bone marrow-mononuclear cells (BM-MNCs) as a promising treatment approach for pRP-ED. We conducted a phase 1/2 pilot clinical trial of intracavernous autologous BM-MNC injection to treat pRP-ED (NCT01089387). Twelve patients with localized prostate cancer and vasculogenic pRP-ED refractory to maximal medical treatment were divided into four equal groups treated with escalating BM-MNC doses (2×10(7), 2×10(8), 1×10(9), 2×10(9)). Tolerance was the primary endpoint. Secondary endpoints were the effects on erectile function and penile vascularization at 6 mo, as assessed using the International Index of Erectile Function-15 and Erection Hardness Scale questionnaires, and color duplex Doppler ultrasound. We measured the peak systolic velocity in cavernous arteries and assessed endothelial function using the penile nitric oxide release test. No serious side effects occurred. At 6 mo versus baseline, significant improvements of intercourse satisfaction (6.8±3.6, 3.9±2.5, p=0.044) and erectile function (17.4±8.9, 7.3±4.5, p=0.006) domains of the International Index of Erectile Function-15 and Erection Hardness Scale (2.6±1.1, 1.3±0.8, p=0.008) were observed in the total population. Spontaneous erections showed significantly greater improvement with the higher doses. Clinical benefits were associated with improvement of peak systolic velocity and of % penile nitric oxide release test and sustained after 1 yr. Our results need to be confirmed by phase 2 clinical trials. PATIENT SUMMARY: We report a phase 1/2 pilot clinical trial investigating cell therapy with injection of bone marrow mononucleated cells to treat postradical prostatectomy erectile dysfunction. No serious side effects occurred. Improvements of erectile function and penile vascularization were noted. Further studies are required to confirm these preliminary results.

Update on 2-year outcomes of the TOMS™ transobturator male sling for the treatment of male stress urinary incontinence.

AIMS: To update the 2-year outcomes of the TOMS™ transobturator male sling for treating post-prostatectomy urinary incontinence (pRP-UI) in a group of patients previously evaluated at 1 year. METHODS: We prospectively followed 40 patients with pRP-UI before and 6, 12, and 24 months after implantation of the TOMS™ transobturator male sling. Urinary symptoms were evaluated using the following questionnaires: USP, ICIQ, UCLA-PCI (urinary bother domain), PGI-I, and daily pad use. Success was defined as patients wearing no or only one security pad. We also report on any other surgical procedures for treating persistent incontinence during the follow-up period. RESULTS: Of 40 patients included in the 1-year follow-up, seven required additional surgical treatment. In the remaining patients (n = 33), significant improvement (P < 0.001) compared to baseline was seen, and a subsequent tendency (non-significant) toward impairment was noted throughout the three postoperative follow-ups for the ICIQ (14.4 ± 4.4 [baseline], 7.6 ± 5.7 [6 months], 8.1 ± 5.6 [12 months], 8.9 ± 5.5 [24 months]), USP-stress urinary (6.7 ± 2.2, 2.8 ± 2.4, 2.8 ± 2.4, 3.2 ± 2.8), ULCA-PCI-urinary bother (10.0 ± 12.5, 66.0 ± 33.0, 64.0 ± 31.5, 62.0 ± 30.7) scores, and pad use (2.5 ± 1.2, 0.7 ± 1.1, 0.8 ± 1.2, 0.9 ± 1.2). Significant impairment in postoperative PGI-I (6.2 ± 0.9, 6.1 ± 0.9, 5.8 ± 1.1, P = 0.028) and USP-overactive bladder symptoms scores (5.4 ± 3.6 [6 months] vs. 6.6 ± 3.7 [24 months], P = 0.046) were noted. A total of 18 (54.5%), 17 (51.5%), and 15 (45.5%) patients wore no postoperative pad, respectively. CONCLUSION: Approximately half of the patients continue to wear no pad 2 years after TOMS™ transobturator male sling implantation. However, a tendency toward impaired continence, possibly associated with overactive bladder symptoms, was noted.

Is it worth continuing sexual rehabilitation after radical prostatectomy with intracavernous injection of alprostadil for more than 1 year?

INTRODUCTION: Intracavernous alprostadil injection (IAI) is a widely used treatment for sexual rehabilitation (SR) after radical prostatectomy (RP). It is unknown whether the continuation of IAI beyond 1 year continues to improve erectile function. AIMS: To assess evolution of sexual function in patients using IAI who are nonresponsive to phosphodiesterase type 5 inhibitors (PDE5i) between 12 (M12) and 24 (M24) months after RP. METHODS: We retrospectively studied 75 men with a nerve-sparing laparoscopic RP, who had normal preoperative erectile function, and who regularly used IAI for SR for at least 24 months. At M12, no patients had responded to PDE5i. MAIN OUTCOME MEASURES: At 12 and 24 months, sexual function was assessed with the UCLA Prostate Cancer Index (UCLA-PCI), International Index of Erectile Function (IIEF)-15, and erection hardness score (EHS) with and without IAI. We also assessed the satisfaction rate with IAI, injection-related penile pain, and satisfaction of treatment. Statistical analysis was performed by using t-tests for paired data and Spearman's rho correlation coefficients to assess the relationships between scores at M12 and M24. RESULTS: Improvement of nocturnal erection was noted (UCLA-PCI, question 25); however, no significant difference was found for IIEF-erectile function with (19.60 ± 9.80 vs. 18.07 ± 10.44) and without IAI (4.63 ± 2.93 vs. 4.92 ± 4.15), UCLA-PCI-sexual bother (37.14 ± 21.45 vs. 37.54 ± 19.67), nor the EHS score with (2.97 ± 1.30 vs. 2.57 ± 1.30) and without IAI (0.67 ± 1.11 vs. 0.76 ± 0.10). The rate of satisfaction with treatment decreased over time (66.6% vs. 46.7%, P = 0.013). Improved response to IAI at M12 was not correlated to improvement in spontaneous erections at M24. CONCLUSION: The response to IAI remained stable after 2 years of treatment, and no significant improvement of spontaneous erections during intercourse attempts was found between M12 and M24. Patients should be informed of the limited effect of IAI on natural erections after 1 year. Yiou R, Bütow Z, Parisot J, Binhas M, Lingombet O, Augustin D, de la Taille A, and Audureau E. Is it worth continuing sexual rehabilitation after radical prostatectomy with intracavernous injection of alprostadil for more than 1 year? Sex Med 2015;3:42-48.