Preventing radiotherapy-associated sexual dysfunction in prostate cancer

Sexual dysfunction is a common and distressing side effect of prostate cancer treatment. Two new reports from randomized clinical trials offer mixed results for adjuvant pharmacotherapy intended to prevent erectile dysfunction in men undergoing radiotherapy for prostate cancer. Despite its success in treating erectile dysfunction after it has already emerged, one study found that tadalafil does not prevent the loss of sexual function during radiotherapy. But a separate study suggests that daily sildenafil citrate therapy helps to prevent radiotherapy-associated erectile dysfunction and declines in libido. Early and continuing communication about potential sexual side effects associated with prostate cancer radiotherapy, is important and frequently welcomed by patients.

Erectile dysfunction, declines in libido and enjoyment of sex, altered orgasm, loss of ejaculation, testicular atrophy, and other sexual changes can contribute to—and be exacerbated by—the anxiety and fatigue associated with prostate cancer and its treatment.^1-4

Radiotherapy, alone or in combination with other interventions, is associated with erectile dysfunction, and 40% of men report erectile dysfunction after undergoing prostate radiotherapy.¹ Physical changes and body feminization (reduced muscle mass, female weight gain patterns, hot flashes, hair loss) can impact patients’ self-esteem and body image, although these appear to be more associated with androgen blockade than radiotherapy per se.² Neoadjuvant androgen blockade hormone therapy plus radiotherapy, but apparently not radiotherapy alone, can result in penile shortening.^5,6

The mechanisms underlying the association between radiotherapy and erectile dysfunction are not yet well-understood, but appear to involve damage to penile vasculature and smooth muscle, endothelial dysfunction, and fibrotic scarring.¹ Pharmacotherapy with phosphodiesterase type 5 inhibitor (PDE5) drugs, such as tadalafil (Cialis) or sildenafil citrate (Viagra), are used to treat erectile dysfunction after radiotherapy, and may work in part because they reduce endothelial dysfunction.¹

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Interest in PDE5 pharmacotherapies’ value as a prophylactic against the emergence of erectile dysfunction during radiotherapy led to two recently reported randomized prospective clinical trials. One of these, a multicenter placebo-controlled, double-blind, randomized study of 221 evaluable study participants with intact erectile function before radiotherapy, yielded disappointing results: daily tadalafil administered during external-beam or brachytherapy radiotherapy over 24 weeks did not prevent the loss of sexual function at 28 to 30 weeks, compared with placebo (79% vs 72%; P = .49).¹ At 1-year follow-up, erectile dysfunction rates were nearly identical between the men assigned to receive tadalafil and those in the study’s placebo group (28% vs 29%).¹ Nor was daily tadalafil associated with improved overall sexual function or sexual and marital satisfaction.¹ Study participants had not undergone androgen blockade within the past 6 months, so the results appear to specifically address radiotherapy-associated sexual dysfunction.¹

Based on their findings, the team concluded that use of PDE5 inhibitors to prevent erectile dysfunction after highly conformal external radiotherapy or low-dose-rate brachytherapy is not supported.¹ However, the authors acknowledged that a different dosing regimen (their study employed tadalafil 5 mg daily) or use of another PDE5 drug could yield different results.¹

Indeed, a similar study of another PDE5 drug, sildenafil, administered before, during, and after radiotherapy for prostate cancer, seems to offer reason for continued hope that PDE5 can prevent radiotherapy-associated erectile dysfunction.⁷ That study, supported in part by Pfizer, found that adjuvant daily sildenafil citrate during and after radiotherapy better preserved erectile function at 12-month follow-up than did placebo (73% vs 50% reporting mild or no erectile dysfunction; P = .024).⁷ Men in the sildenafil group also reported modestly significant higher sexual desire scores (P = 0.049).⁷ At 2 years after initiation of treatment, erectile function remained better among men who had taken adjuvant sildenafil (82% vs 56%; P = .045).⁷