Half of long-term erectile function (EF) loss after brachytherapy (BT) is due to aging


One of the most important things we patients want to know about any treatment is what kind of potency we can expect afterwards. Urinary and rectal dysfunctions are often measured and reported by investigators, but sexual dysfunction is rarely reported or measured.

While there is at least some consensus on the use of the National Cancer Institute-defined common terminology criteria for adverse events (CTCAE 4.0) to grade urinary and rectal adverse events, there seems to be no consensus on how to measure sexual dysfunction. It is reported in a wide variety of different, non-comparable ways, if it is reported at all.

Several definitions are used in studies: IIEF/SHIM, EPIC-sexual status score, erection sufficient for intercourse, actual intercourse in the last month, and/or whether erection aids are needed or helpful. Often results are given among men who were previously potent or high-scoring only. Others report return to baseline function, where “return” may be defined as anywhere from within 1 point on IIEF/SHIM to any value within the population standard deviation.

From the patient’s point of view, we would love to have a nomogram that could predict our probability of potency after any given treatment.

In 2011, Alemozaffar et al. (see The “New” Prostate Cancer InfoLink commentary) reported comparable figures on erectile function at 2 years after surgery (RP), external beam radiotherapy (EBRT), and brachytherapy (BT). They found that functional erection preservation could be predicted for each kind of therapy based on pre-treatment sexual function (EPIC scores), age, and a few other variables that varied with the type of treatment. However, there is a problem in the way they used baseline EPIC scores and age in their predictive model. The problem is that EPIC score is not independent of age — it is a function of age, especially in the age group studied. This problem, called covariance, violates a basic assumption of the model. The problem of covariance could have been fixed by using an age-adjusted EPIC score (much as we use inflation-adjusted constant dollars in economic analyses). The University of Michigan, which did the validation study, must have a validated file of EPIC scores by age for a random sample of healthy men. Those scores, expressed as a percent, can become an indexing factor that will be divided into each respondent’s EPIC score according to his age.

We can easily see the “age problem” in the following table from the appendix (eTable3) of the paper by Alemozaffar et al., which shows the percentages of men with functional erections after 2 years by age:

 

PictureA

Although the potency doesn’t seem to vary much between treatments in total (range 35 to 43 percent), it is only because the men who received EBRT and BT were older than the men who were treated with RP. Within every age group, potency preservation was higher with radiation.

Conventional wisdom is that radiation erodes potency slowly over time, while surgery affects potency at the beginning with some return over the first 2 years. The study only looked at potency at a single point in time, 2 years after treatment. This may obscure the long-term effect of radiation treatment on erectile function. This is more than just a technicality. As we measure potency after treatment for say 5 or 10 years, we want to be able to separate treatment effects from age effects. In the 60- to 75-year age range that includes most treated patients, we expect potency to deteriorate naturally as we age, but what portion of that deterioration is because of the treatment?

Katz and Kang, in a 7-year follow-up study of quality of life following SBRT treatment, found that there was a brief early decline and recovery followed by a gradual long-term decline (see Figure 5 of the actual paper). After 7 years, patients’ potency was about 67 percent of their original EPIC score. The authors point out:

In fact, potency preservation rates after SBRT are only slightly worse than what one would expect in a similar cohort of men in this age group, who did not receive any radiotherapy.

However, they made no attempt to separate the effects of treatment from the effect of natural aging.

In a new analysis of the erectile function after low dose rate (LDR) brachytherapy, Keyes et al. made the first such attempt to separate the impact of the two effects. They analyzed the erectile function of 2,929 favorable-risk brachytherapy patients based on data recorded by the British Columbia Cancer Agency between 1989 and 2012.

  • The men were categorized at the baseline visit by their doctors as having full (79 percent), partial (8 percent) or no (13 percent) erectile function. The men were re-categorized on follow-up visits by their doctors.
  • The patients’ median age was 66 at treatment.
  • 33 percent had hypertension; 10 percent had diabetes.
  • 44 percent also received adjuvant ADT (which typically began 3 months before treatment and continued 3 months after, and was given to men with larger prostates or higher risk; it was rarely used after 2005).
  • The men self-evaluated potency on follow-up visits using the Sexual Health Inventory for Men (SHIM) questionnaire.
  • All men in the study had at least 10 months of follow up and as long as 14.1 years (median 3.5 years).

Expected erectile function by age without treatment was predicted in two ways:

  • The Massachusetts Male Aging Study (MMAS) predicts annual impotence rates of:
    • 12.4 cases per 1,000 for men of 40 to 49 years
    • 29.8 cases per 1,000 for men of 50 to 59 years
    • 46.4 cases per 1,000 for men of 60 to 69 years
    • These were estimated in 5-year increments.
  • Baseline erectile function of men 5 years older was used as the level expected if there had been no treatment.

The authors report the following results:

  • There was a large decline in erectile function (EF) at the first (6 week) follow-up visit:
    • EF loss of 25 to 35 percent if they had no ADT. (The authors attribute this to trauma and psychological factors rather than dose to erectile vasculature and structures.)
    • EF loss of 80 to 85 percent if they had adjuvant ADT.
  • The EF of those who didn’t have ADT continued to decline gradually.
  • The EF of those treated with adjuvant ADT rose back up to the level of the other men at the 2-year mark, and then similarly declined.
  • Among men fully potent at baseline, about 50 percent were fully potent at 5 years and an additional 10 percent were partially potent.
  • Among men fully potent at baseline, about 40 percent were fully potent at 7 years and an additional 15 percent were partially potent.
  • The following table shows potency by age group after 7 years.

PictureB

  • About 30 percent of the fully potent men used PDE5 inhibitors.
  • Diabetes and hypertension significantly affected EF; radiation dose did not.
  • The following table shows actual and expected potency losses due to by age group.

PictureC

  • About half of the long-term decline in EF was due to normal aging effects.
  • Most of the steep early decline is due to BT; most of the gradual later decline is due to aging.

This study goes a long way towards providing the data patients need to make a treatment decision. The patient wants to know, for each potential treatment, what his odds are of preserving functional erections at some future point in time. To build a database capable of answering his question, clinicians offering each treatment will have to collect the following data at baseline and follow-up visits:

  • EPIC score (age adjusted)
  • Age at treatment
  • Co-morbidities: cardiovascular disease, hypertension, diabetes, neuropathy, depression, hypogonadism
  • Medications: β-blockers, testosterone supplementation, ADT, opiates, adrenergics, etc.
  • Smoking
  • Substance abuse
  • Obesity
  • Married/sex partner

We are hopeful that someday clinicians will arrive at a consensus about collecting the data, measuring, and reporting potency. Patients can further this goal by letting their doctors know that this is important to them. Judging by how seldom reports like this are published, many doctors think it is not very important.

Editorial comment: This commentary was written by Allen Edel. We also thank Dr. Mira Keyes, Head of the Provincial Prostate Brachytherapy Program of the British Columbia Cancer Agency, Vancouver Cancer Centre, for making the full text of the article available to us.

4 Responses

  1. It would be helpful to add heart and circulatory illness as a variable.

  2. Dear gmac53:

    Those would be included under “Cardiovascular” disorders, which are explicitly mentioned above.

  3. I would have been happy to have any of my treating doctors even ask about sexual function. I was/am amazed at the level of discomfort discussing the subject that I noticed, even in urology. I hope that can change. I felt pretty lonely on one of the most important parts of my lifestyle. At 56 it was pretty important. Now at 73 my wife and I are resigned to the impotence.

  4. Dr. Daniel Hamstra corrected me about where the EPIC scores are available. He wrote,

    “In regard to the JAMA analysis from several years ago I think you again are misled by attributing institutions where they do not belong. That JAMA study was done almost entirely at Beth Israel Deaconess and Emory with the validation set from the CAPSURE data from UCSF. Although the PROSTQA study started at UM since the PI (Marty Sanda) left UM almost 10 years ago it has been based first in Boston and then in Atlanta.”

    He also provided his insights into that study, which I think are important and worth quoting:

    “I think you caught the main difference between surgery and RT modalities such that this statement:

    “In 2011, Alemozaffar et al. (see The “New” Prostate Cancer InfoLink commentary) reported comparable figures on erectile function at 2 years after surgery (RP), external beam radiotherapy (EBRT), and brachytherapy (BT).”

    although factually true was a “positive spin” that the urology authors placed on this analysis. Those of us who are in RadOnc tried to fight it, but all we really could get was having them put the gross numbers in without making any adjustments for either age (which would affect baseline function and decline over time) and baseline function.

    “Because of age and patient selection, the men who underwent RP had better sexual function to begin with. Prior to treatment 83% of men getting RP did NOT have sexual dysfunction by the EPIC while this number was 67% for brachytherapy and 53% for EBRT. These numbers also parallel the age differences with RP << BT < EBRT. However, at two years, preserved sexual function was found in 37%, 43%, and 43% (RP, BT, EBRT). So, for those with sexual function prior to treatment, even after adjusting for age, RT (of either sort) preserved function much better, which was 45% preservation for RP, and 64% for BT, and 70% for EBRT. After adjusting for age, the difference with either RT modality was even greater.

    “The timing of decline of sexual function as you noted is also not what people usually report for RT. I'm not sure where the "old wives tale" came from. But what is always talked about is that RP causes an immediate decline with a slow recovery for 1-2 years while RT shows a stability initially with a slow decline over 2 years. I think, as you noted, studies like PROSTQA, Katz, and the BC brachytherapy study all seem to support that with RT the decline is much faster (often even in the first several months) with some patients later having a modest recovery, and then all followed by the relentless (likely age induced) decline over time.

    “This is frankly what others had seen previously but somehow the wives tale stood. See for instance

    Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):31-5. doi: 10.1016/j.ijrobp.2009.01.070.
    "Time of decline in sexual function after external beam radiotherapy for prostate cancer."
    Siglin J, Kubicek GJ, Leiby B, Valicenti RK.

    “Their first time points was 6 months, and by this point about half the decline they were going to see had already occurred.”

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