THE "NEW" PROSTATE CANCER INFOLINK

Erectile function after radiation therapy is of great interest to many men trying to decide between surgery and radiation, and to decide among the several radiation treatment options. Dess et al. reported the outcomes of men who received stereotactic body radiation therapy (SBRT), often known by the brand name CyberKnife.

Between 2008 and 2013, 273 patients with localized prostate cancer were treated at Georgetown University. All patients filled out the EPIC questionnaire at baseline, which includes several questions on erectile function. The authors focused on the question asking whether erections were firm enough for intercourse, irrespective of whether they used ED medications or not. A similar questionnaire, SHIM, was also used, but results were similar. Answers were tracked over time with analyses at 2 years and at 5 years. Importantly, the median age at baseline was 69 years.

Here are the core results of this study:

• About half the men had functional erections at baseline
• At about 2 years of follow-up, among those with functional erections at baseline, 57 percent retained potency.
• The largest loss occurred by 3 months after treatment, with about two-thirds retaining potency at 3 months.
• Two-thirds retained potency at 3 months regardless of age.
• Men under 65 suffered no further loss of potency, even after 5 years,
• Men 65 and over continued to lose potency,
  • About half retained potency at 2 years
  • About 40 percent retained potency at 5 years

The authors also looked at other causes of erectile dysfunction, including partner status, body mass index (BMI), diabetes, cardiovascular disease, depression, baseline testosterone levels, and baseline use of erectile dysfunction (ED) medications. None of those, except BMI, had a statistically significant effect in this patient population at 2 years post-treatment.  Some gained importance by 5 years, but because they are age dependent, and also affect baseline ED, none except BMI were independently important after baseline function and age were accounted for. A few known risk factors for ED were not included: medications (e.g., beta-blockers, testosterone supplementation, etc.), smoking, and substance abuse.

There is a source of statistical error called co-linearity, which arises when two variables, like baseline potency and age, are substantially interlinked. Although they were independently associated with erectile function, there is considerable overlap. It may be useful to separate the effect of one from the other. This is accomplished by using age-adjusted baseline erectile function in the same way that economists look at inflation-adjusted gross national product (GNP). I hope the authors will look at this. As we saw, an analysis of brachytherapy utilizing a different technique showed that half of the loss of potency among men who had brachytherapy was due to aging.

The effect of age on potency preservation cannot be overemphasized. Undoubtedly, radiation can cause fibrosis in the penile artery, and fibrosis is worse in older men. But, contrary to a prevalent myth, those radiation effects occur very early. Following that early decline, the declines in potency are primarily attributable to the normal effects of aging (which include occlusion of the vasculature supplying the penis.) As we’ve seen in other studies, most of the radiation-induced ED will show up within the first 2 years, and probably within 9 months of treatment. This was shown for 3D-CRT in the ProtecT clinical trial, for brachytherapy, for SBRT, and for EBRT.

Looking at other reports of potency preservation following SBRT, the Georgetown experience (57 percent potency preservation) seems to be on the low end. There has only been one report of lower potency preservation: 40 percent at 3 years among 32 patients. An earlier report from Georgetown reported 2-year potency preservation at 79 percent at 24 months. Dr. Dess explained that the earlier report included men with lower potency at baseline. However, because baseline potency is highly associated with post-treatment potency, the outcomes should be in the other direction. The discrepant data are puzzling. At 38 months post treatment, Bernetich et al. reported potency preservation in 94 percent among 48 treated patients. Friedland et al.  reported 2-year potency preservation at 82 percent. Katz reported potency preservation of 87 percent at 18 months. Although, different patient groups may respond differently, it is difficult to understand why potency preservation was so much lower in the current study. These discrepancies argue for a more standardized approach to analyzing erectile function after treatment, and the present study makes a good start towards that goal.

Compared to other radiation therapies, SBRT fares well. Evans et al. looked at SBRT at Georgetown and two 21st Century Oncology locations and compared it to low-dose-rate brachytherapy (LDR-BT) and IMRT as reported in the PROSTQA study. At 2 years, among patients who had good sexual function at baseline, EPIC scores declined by 14 points for SBRT, 21 points for IMRT, and 24 points for LDR-BT. The minimum clinically detectable change on that measure is 10 to 12 points. There has been only one randomized trial comparing extreme hypofractionation to moderate hypofractionation. In that Scandinavian trial, they used an older technique called 3D-CRT, which would never be used today to deliver extreme hypofractionation (at least, I hope not!). In spite of the outmoded technology, sexual side effects of the two treatments were no different. In an analysis from Johnson et al. comparing SBRT and hypofractionated IMRT, the percentage of patients reporting minimally detectable differences in sexual function scores was statistically indistinguishable in spite of the SBRT patients being 5 years older.

Dess et al. also looked at sexual aid utilization in a separate study on the effect of SBRT. They found that:

• 37 percent were already using sexual aids at baseline.
• 51 percent were using sexual aids at 2 years.
• 55 percent were using sexual aids at 5 years.
• 89 percent of users say they were helped by them at baseline, at 2 years, and at 5 years.
• 86 percent used PDE5 inhibitors only (i.e., Viagra, Cialis, Levitra, or Stendra).
• 14 percent combined a PDE5 inhibitor with other sexual aids (e.g., Trimix, MUSE, or a vacuum pump).

Erectile function is well-preserved following SBRT, and seems to be as good or better than after IMRT, moderately hypofractionated IMRT, or LDR brachytherapy. Based on reports of a protective effect of a PDE5 inhibitor, patients should discuss their use with their radiation oncologist starting 3 days before radiation and continuing for 6 months after. High levels of exercise and frequent masturbation may have protective effects as well.

Editorial note: This commentary was written by Allen  Edel for The New” Prostate Cancer InfoLink. Allen Edel wishes to thank to Drs. Daniel Spratt and Robert Dess for allowing him to see the full texts of their studies.

Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: dysfunction, erectile, function, radiation, therapy |