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<p><b>INTRODUCTION: </b>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.</p><p><b>AIMS: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>MAIN OUTCOME MEASURES: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p>