Erectile dysfunction (ED) is one of the most common complications after radical prostate cancer surgery (RP), which seriously affects the quality of life of patients after surgery (1). In the past, due to the excessive focus on cancer treatment by both doctors and patients, ED after RP was often neglected, especially in China, where most prostate cancer patients were close to 70 years old at the time of RP surgery and had different degrees of ED before surgery or already had no normal sexual life. However, with the rapid increase in the incidence of prostate cancer in China in recent years and the widespread implementation of PSA screening, the proportion of early prostate cancer and young prostate cancer patients detected has increased. While these patients are concerned about cancer treatment, they are also bound to be worried about the adverse effects of surgery on their quality of life, especially their sex life. Therefore, it is particularly important to pay attention to ED in post-operative RP patients and to actively pursue rehabilitation. Etiology of ED after RP Prostate cancer patients may develop ED immediately after RP surgery, and even if the cavernous nerves are preserved during surgery, it takes 2-4 years for patients to gradually regain erectile function without any rehabilitation, which is called the “nerve palsy” period (2). The main causes of nerve palsy include ischemia due to strain on the cavernous nerve during RP, thermal burns from the electric knife, inflammatory injury from surgery or damage to the blood vessels that feed the nerve (3). The loss of daytime and nighttime erections due to nerve paralysis causes hypoxia in the cavernous body of the penis, leading to collagen deposition, apoptosis and fibrosis of smooth muscle cells, resulting in venous leakage from the cavernous body and permanent ED, a mechanism that has been confirmed by in vivo experiments in animals (4). In addition, ligation of the geniculate branch of the internal pubic artery during RP, resulting in reduced perfusion of the penile artery, is another important cause of ED after RP surgery (5). It is due to the breakthroughs in the etiology of postoperative RP ED that more and more physicians and patients are accepting and using penile rehabilitation to treat postoperative RP ED. Penile rehabilitation refers to the use of non-surgical therapies such as medications and assistive devices to restore or preserve penile erection during or after RP (6). function (6). The simplest approach is for the patient to attempt to make the penis erect or enlarged after sexual stimulation to increase the blood supply to the penile corpus cavernosum for the purpose of rehabilitation. However, clinically, patients rarely achieve an effective penile erection in the early post-RP period without relying on medications or assistive devices. Commonly used rehabilitation therapies include oral PDE-5 inhibitors, vacuum negative pressure erection device (VED), intracavernous penile drug injection (ICI), intraurethral drug delivery (MUSE) and combination therapy. PDE-5 inhibitors Patients with cavernous nerve paralysis after RP surgery can no longer synthesize NO by neuronal nitric oxide synthase (nNOS), so they mainly rely on endothelium-derived and inducible nitric oxide synthase (eNOS, iNOS) synthesis. PDE-5 inhibitors can increase the level of cGMP and amplify the NO signaling pathway, thus improving the blood supply to the penis and inhibiting cavernous fibrosis. Studies have shown that three PDE-5 inhibitors, sildenafil, vardenafil, and tadalafil, improve erectile function, intercourse success, and sexual satisfaction in patients with ED after RP surgery (7-9). However, there is no consensus on the timing of initiation, optimal dose, optimal duration of therapy, and patient selection for these three drugs in patients with postoperative ED after RP, and there is a lack of prospective randomized controlled studies with large samples. Overall, most experts believe that PDE-5 inhibitors should be started 2-4 weeks after RP surgery, once a night, at a small dose (sildenafil 50 mg, vardenafil 10 mg), for at least 6-9 months. The effect of taking PDE-5 inhibitors on demand before each sexual encounter has been reported to approximate the effect of taking them every night (7). However, it should be noted that the efficacy of PDE-5 inhibitors is significantly correlated with whether the nerve is preserved during RP, with 35-75% efficacy of sildenafil in patients with nerve-preserved ED compared to 0-15% in those without nerve preservation (10). Vacuum negative pressure erection device (VED) VED induces erection by increasing blood supply in the cavernous body of the penis through negative pressure, while a pressure constriction ring is tied at the root of the penis to block venous return in the cavernous body to maintain erection. Animal experiments have shown that VED can improve hypoxia within the penile corpus cavernosum and inhibit smooth muscle cell apoptosis and cavernous fibrosis (11). As a non-invasive means of rehabilitation, the long-term efficiency and patient satisfaction rate of VED for the treatment of ED from all causes exceeds 80% (12). In patients with ED after RP surgery, the success rate of sexual intercourse after VED application is up to more than 90% (13). It is currently believed that patients can start VED rehabilitation 1 month after RP (after catheter removal), either daily or every other day, for about 10 minutes each time, and that sexual intercourse using a pressure constriction ring should be attempted preferably 2 months after RP (14, 15). In addition to this, VED can prevent the development of penile atrophy in patients after RP surgery (14). Intracavernosal drug injection (ICI) ICI was the first method used for penile rehabilitation in patients with ED after RP surgery. By injecting vasodilators such as prostilbestrol (PGE1), it reduces tissue damage caused by hypoxia in the penile corpus cavernosum and restores erectile function by relaxing cavernous smooth muscle. Randomized controlled studies and long-term follow-up data have shown that ICI improves erectile function by increasing the rate of spontaneous penile erection (up to 67%) and increasing penile hardness in patients with ED after RP (16, 17). However, ICI is a slightly invasive tool, and patient compliance with its use is therefore reduced. Currently, ICI is mainly used in patients with ED who have failed oral PDE-5 inhibitor therapy or have contraindications, usually three times a week for more than three months. Intraurethral administration (MUSE) MUSE is a semi-solid suppository of prostaglandin (PGE1) that is injected through an applicator into the distal urethra, where it is rapidly absorbed through the urethral mucosa and reaches the cavernous smooth muscle of the penis to induce an erection. Studies have shown that after three months of MUSE treatment, 70.3% of post-RP ED patients regained penile erection and had a success rate of intercourse of 57.1% (18). A controlled multicenter randomized study with PDE-5 inhibitors showed that once-per-night MUSE (125-250ug) and sildenafil 50mg per night had similar rates of erectile function restoration (19). However, the shortcomings of this therapy are the penile pain, urethral pain, and vaginal discomfort of the sexual partner induced by PGE1, and 32% of the patients abandoned the treatment because of this (20). Currently, MUSE is also used mainly in ED patients who have failed oral PDE-5 inhibitor therapy or have contraindications, usually three times a week for more than three months. Combination therapy Patients with postoperative ED after RP who are poorly treated with PDE-5 inhibitors alone, combined with VED, ICI or MUSE at the same time, can improve the therapeutic effect while appropriately reducing the drug dose of ICI or MUSE and alleviating the therapeutic side effects of the latter (21). However, there are few reports of combination therapy for penile rehabilitation after RP surgery, and most of the available literature is a retrospective case study, lacking multicenter randomized controlled studies, so no definite conclusion can be drawn yet. Conclusion Over the past 15 years, the rehabilitation of post-RP ED has moved from theory to practice, enabling many patients who originally suffered from ED to regain erectile function and satisfactory sexual life. However, at the same time, the rehabilitation treatment of ED after RP also faces many challenges, such as the optimal time to start rehabilitation treatment after RP, the optimal dosage and optimal regimen of medication use, the maintenance time of rehabilitation treatment and the optimal method, etc. There are still no uniform standards and guidelines, and a large sample of multicenter randomized controlled studies are needed.