Impact of Prostate Cancer Treatments on Sexual Health

Functional Anatomy of Erection

The penis consists of a paired corpora cavernosa dorsally and the corpora spongiosum ventrally, which contains the urethra. The tunica albuginea surrounds the corpora cavernosa. Blood flow is supplied by the internal iliac artery then the internal pudendal artery. The internal pudendal artery becomes the common penile artery and divides into the cavernosal, dorsal, and bulbourethral arteries. The cavernosal arteries supply the helicine arterioles, which open into the endothelial-lined lacunar spaces. The blood flow returns as these endothelial spaces drain into subtunical venules, which coalesce to form emissary veins. The emissary veins traverse the tunica to empty into the cavernosal, deep dorsal, or spongiosal veins where they drain into the prostatic venous plexus or the internal pudendal veins. Accessory pudendal arteries (APA) arise from a source above the levator ani (iliac, femoral, vesical, or obturator arteries) and travel down to the perineum in the periprostatic region.

Physiology of Erection

In the flaccid state, cavernosal smooth muscle (SM) remains contracted under adrenergic control. With sexual stimulation, nerve impulses cause SM relaxation of the arteries and arterioles supplying the penis, facilitated by the nitric oxide (NO)/cyclic guanine monophosphate pathway (cGMP), and leading to an increased penile blood flow. Simultaneously, relaxation of the cavernosal SM allows the filling of lacunar spaces and compression of the subtunical venous plexuses, therefore blocking most of the venous drainage system and creating an erection.

Pathophysiology of ED after Radical Prostatectomy

The pathophysiology of ED after radical prostatectomy (RP) involves the interaction of three factors: neural injury, vascular injury, and corporal SM damage. Additionally, the extent and reversibility of these injuries ultimately will define the recoverability of erectile function (EF) ( Table 62.1 ).

Pathophysiology of ED after RT

The etiology of post radiation therapy (RT) ED is not completely understood and is likely multifactorial. Obayomi-Davies et al. state that the radiation may cause dose-dependent damage to the neurovascular bundles, the crura, and the penile bulb. Zelefsky and Eid evaluated 98 patients for ED after RP or RT, with Duplex ultrasonography and classified them as having arteriogenic, cavernosal, mixed, or neurogenic impotence. Thirty-eight patients were treated with RT and of these 24 (63%) were found to have arteriogenic dysfunction. This finding differed from post-RP patients who were more likely to have a cavernosal veno-occlusive dysfunction (CVOD). Endothelial cells are damaged in a time- and dose-dependent manner. These endothelial cells line the penile arteries and sinusoids of the corpora cavernosa. The capillaries and sinusoids are especially sensitive because endothelial cells are major cellular components. Damage to these cells leads to luminal stenosis and arterial insufficiency, which have a gradual progression over time. Pathologic evaluation of the small vessels shows hyalinization, fibrosis, and the deposition of lipid-laden macrophages. The net effect of this endothelial damage is ischemia. Pisansky et al. theorized that ED after RT is related to cavernosal hypoxia and fibrosis causing penile endothelial dysfunction.

Pathophysiology of ED after ADT

The relationship of ED and androgen deprivation therapy (ADT) is primarily related to the lack of testosterone. In castrated men, erections are less frequent due to loss of libido and the absence of nocturnal erections. Testosterone has effects on tumescence (positive effect on NO synthase and negative on Ras homolog gene family member A (RhoA) / Rho-associated coiled-coil containing protein kinase (ROCK)) and detumescense (positive effect on PDE5); however, the net effect is modest overall. In a study by Suzuki et al., erectile response was measured in castrated male rats (model for venous leak) after electrical stimulation. The castrated rats had significantly decreased responses to stimulation compared to their noncastrate controls and after testosterone replacement, erectile responses were recovered. This study showed that testosterone plays an important role in the neural pathways for tumescence. ADT also has indirect effects on the maintenance of endothelial and cavernosal SM. The absence of erections with ADT, leads to a decrease in cavernosal oxygenation creating an environment of prolonged absence of cavernosal oxygenation. This leads to the inhibition of PGE, which allows TGF-β1 to promote connective tissue synthesis (primarily collagen), and the replacement of trabecular SM. The change in SM/collagen ratio leads to a decreased ability for the SM to expand and occlude the subtunical venous plexuses, leading to venous leak.

Prevalence of ED after RP

A review of the existing medical literature demonstrates a large variance in reported rates of ED following RP (20–90%). There are multiple reasons for these reported differences in outcomes including intrinsic patient factors, surgical factors, and reporting biases. Compared to postoperative complications like incontinence, ED is harder to characterize; the return of EF may be masked by the expected decline in function due to advancing age. Therefore, measuring EF prospectively has a moving baseline. There is a significant psychological component for these men and their partners; however, it is poorly described in literature.

Perhaps the gold standard recovery definition, the International Index of Erectile Function (IIEF) EF domain score of 26 is unequivocally normal, and in a study by Teloken et al., approximately 70% of men with EF domain scores of 22–25 agreed completely or somewhat with the statement that “they could have sexual intercourse whenever they wished.” Functional erectile ability likely lies somewhere between 22 and 26 on the EF domain score. Additionally, we believe that men who score 26 points or greater on the IIEF EF domain while using a PDE5i or other erectogenic agent are not truly normal.

The prevalence of ED following contemporary RP is poorly defined by the current peer-reviewed literature. The published studies have numerous methodological flaws, such as absence of consensus on a definition of success or failure to recover erections, small populations, incomplete data acquisition, limited data on quality of life and satisfaction with sexual life, and inadequate patient follow up. Mulhall et al. performed a comprehensive review of the literature, a composite prevalence rate among men following contemporary RP was 48% and where the nerve-sparing status was described, EF recovery was achieved in 50%. It is safe to state that centers reporting EF recovery rates of 90% or higher are giving patients unrealistic expectations as they are unsubstantiated in the general RP population. Katz et al. showed that 20% of men with functional erections 3 months after RP would lose their erections by 6 months, and 90% of those who were functional at 3 months would retain or regain function at 12 months. In a study by Rabbani et al., they illustrate that younger age is associated with EF recovery beyond 2 years in patients who had a BNS RP. In a more recent study by Sivarajan et al., EF showed significant improvements after RP up to 2 years, from 2 years to 10 years EF remained generally stable; however, men <60 were more likely to report improvements up to 7 years after RP when compared to older men.