What to expect after prostate radiation (acute side effects)

Urinary, rectal and sexual side effects of treatment are usually mild and transient, although they may be worse if you are especially sensitive to radiation, are an older man, or had symptoms before you started radiation therapy. Some side effects described below may occur in many men starting anytime from a week to a month after treatment and continuing for weeks or months. The duration and intensity vary greatly between men.

If any of those symptoms interfere with your day-to-day living, call your doctor. He may be able to prescribe medication that can help alleviate those symptoms.

Urinary

Total incontinence is uncommon. There may be some leakage or dribbling. Other common side effects are irritation, burning or bleeding while urinating, feeling like you have to urinate immediately even when you know your bladder isn’t full, having to wake up several times during the night to urinate, or having to urinate frequently during the day. You may pass small amounts of blood or blood clots; however, if you are bleeding copiously when you urinate, contact your doctor immediately.

A rare but potentially serious side effect is urinary retention. If you find that you can’t urinate even though your bladder feels full, go to the Emergency Room of the nearest hospital immediately and tell them you are suffering from urinary retention. They must catheterize you to allow the urine to flow out.

Rectal

There may be a feeling like you have to pass a stool but you cannot, and this feeling may recur often. This is called tenesmus. You should be aware that that feeling is from inflammation in your rectum (proctitis), not from actual stool there, and if you strain, you may create hemorrhoids. You may have frequent bowel movements. There may be blood in your stools or blood may drip out. Hemorrhoids may occur. Sometimes stool may leak out, especially when you are passing gas. Stool may be loose, or it may be especially hard.

If you have diarrhea for more than a few days, call your doctor. If the bleeding is copious, call your doctor.

Sexual

Semen will usually dry up soon after treatment, although there may be small amounts of fluid. Occasionally, you may see some blood in that fluid or a few drops of blood may drip out after orgasm.

You may notice that, over time, erections are not as hard or as long-lasting. To protect the blood vessels supplying your penis with blood, your doctor may have prescribed Viagra or a similar medication. You should continue to take that medication for at least 6 months after the end of treatment, even though it seems like you don’t need it.

Testosterone levels often drop following radiation, but may eventually return to normal levels. Because of this, you may notice a drop in the level of your sexual desire/libido. Some men experience difficulty reaching orgasm.

If any of the symptoms are bothersome, you may want to consult with a doctor who specializes in Sexual Medicine.


For a list of all side effects, long-term and acute, see:
Adverse Effects of Primary IMRT

What to expect immediately after prostate radiation

Urinary, rectal and sexual side effects of treatment are usually mild and transient, although they may be worse if you are especially sensitive to radiation, are an older man, or had symptoms before you started radiation therapy. Some side effects described below may occur in many men starting anytime from a week to a month after treatment and continuing for weeks or months. These are called "acute" side effects. The duration and intensity vary greatly between men.

If any of those symptoms interfere with your day-to-day living, call your doctor. He may be able to prescribe medication that can help alleviate those symptoms.

Urinary

Total incontinence is uncommon. There may be some leakage or dribbling. Other common side effects are irritation, burning or bleeding while urinating, feeling like you have to urinate immediately even when you know your bladder isn’t full, having to wake up several times during the night to urinate, or having to urinate frequently during the day. You may pass small amounts of blood or blood clots; however, if you are bleeding copiously when you urinate, contact your doctor immediately.

A rare but potentially serious side effect is urinary retention. If you find that you can’t urinate even though your bladder feels full, go to the Emergency Room of the nearest hospital immediately and tell them you are suffering from urinary retention. They must catheterize you to allow the urine to flow out.

Rectal

There may be a feeling like you have to pass a stool but you cannot, and this feeling may recur often. This is called tenesmus. You should be aware that that feeling is from inflammation in your rectum (proctitis), not from actual stool there, and if you strain, you may create hemorrhoids. You may have frequent bowel movements. There may be blood in your stools or blood may drip out. Hemorrhoids may occur. Sometimes stool may leak out, especially when you are passing gas. Stool may be loose, or it may be especially hard.

If you have diarrhea for more than a few days, call your doctor. If the bleeding is copious, call your doctor.

Sexual

Semen will usually dry up soon after treatment, although there may be small amounts of fluid. Occasionally, you may see some blood in that fluid or a few drops of blood may drip out after orgasm.

You may notice that, over time, erections are not as hard or as long-lasting. To protect the blood vessels supplying your penis with blood, your doctor may have prescribed Viagra or a similar medication. You should continue to take that medication for at least 6 months after the end of treatment, even though it seems like you don’t need it.

Testosterone levels often drop following radiation, but may eventually return to normal levels. Because of this, you may notice a drop in the level of your sexual desire/libido. Some men experience difficulty reaching orgasm.

If any of the symptoms are bothersome, you may want to consult with a doctor who specializes in Sexual Medicine.

Adverse Effects of Primary IMRT

A recent commentary listed some of the most common adverse effects of prostatectomy, some of which (e.g., perceived penile shrinkage, climacturia, Peyronie's, stress incontinence) are seldom mentioned by urologists to prospective patients, and are not routinely included in standardized quality-of-life questionnaires. In the interest of providing equal time to the potential adverse effects of radiation, below is a list of such effects, ranked by approximate incidence, for primary IMRT.

This list only applies to primary IMRT and not to salvage treatments, which may have a very different side effect profile. These data are not purely for IMRT – they include some patients treated with 3D CRT as well. Some patients in these studies may have had adjuvant ADT, so it is impossible to distinguish the effects of radiation from the effects of concurrent hormone treatment. None of this applies to SBRT or brachytherapy.

Most of the data on acute side effects are pulled from the Sanda et al. study, which represents the patient-reported outcomes at 9 of the top US institutions, and is not indicative of community practice. Many of the late-terms side effects are given as their absolute incidence. Acute side effects are given as increases over baseline function (indicated by “+”). Unless otherwise specified, they are acute side effects (within 3 months of treatment), rather than late-term or chronic side effects. Acute side effects are typically transient. Contrary to “common knowledge,” new side effects rarely emerge after 2 years.

In general, urinary, rectal and sexual adverse effects will be worse among men whose function is impaired before treatment, and those with certain comorbidities. Radiation dose, image guidance techniques, margins, anatomic differences, and sensitivity to radiation contribute to individual variances in side effects. Most of the side effects are attributable to inflammation (cystitis, urethritis, proctitis), spasms (diarrhea, bladder spasms), and the destruction/fibrosis of vascular and other tissues (ED, urinary retention). There are treatments available for many of these adverse effects. Patients are advised to discuss them with their doctors.

Loss of semen (5 yrs) 89%

Fatigue 32%

Sexual function- big/moderate problem (1 yr) 31%

Frequent urination +18%

Vitality/hormonal function – big/moderate problem (1 yr) 18%

Bowel urgency  +15%

Bowel frequency +14%

Urinary irritation or obstruction – big/moderate problem (1 yr) 14%

Bowel/rectal function – big/moderate problem (1 yr) 11%

Dysuria (pain while urinating) +11%

Weak stream +10%

Leaking >1x per day +9%

Rectal pain +5%

Fecal incontinence +5%

Dribbling +4%

Urinary incontinence – big/moderate problem (1 yr) 4%

Any pad use +3%

Bloody stools +2%

Other rare effects with <1% incidence:

Rectourethral fistula

Bladder neck contracture requiring surgical intervention

Second primary pelvic cancer

------------

Sources:

Prospective evaluation of the prevalence and severity of fatigue in patients with prostate cancer undergoing radical external beam radiotherapy and neoadjuvant hormone therapy.

Quality of Life and Satisfaction with Outcome among Prostate-Cancer Survivors (Sanda et al.)

Preliminary Toxicity Analysis of 3DCRT versus IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial

Radiotherapy-induced second primary cancer (RTSPC) risk is low and may differ by radiation technique.

Urorectal fistulae following the treatment of prostate cancer

Second primary cancers after radiation for prostate cancer: A systematic review of the clinical data and impact of treatment technique

Side effects of salvage radiation – difficult to draw conclusions based on database analyses.

The same researchers (give or take a couple), in analyses of an Italian and US databases, investigated whether it could diminish the side effects of radiation by waiting longer after prostatectomy. The conventional wisdom is that waiting longer allows the newly cut tissues more time to heal completely before the onslaught of radiation.

Unfortunately, the methodology they used for their analyses is problematic. I decided to write about it because it illustrates some of the issues inherent in such database analyses, and raises cautions in drawing conclusions from them.

Hegerty et al. used the US SEER/Medicare database to find 3 groups of patients. All of them had adverse pathology (stage T3 and/or positive margins) after prostatectomy in the period between 1995 and 2007. The three groups were:

1.     RP alone, didn’t have RT (RP only) – 4,509 patients

2.     Adjuvant RT within 9 months of surgery (aRT) -  894 patients

3.     Salvage RT, at least a year after surgery (sRT) -  734 patients

Obviously, this is a large database. The three groups differed somewhat with respect to age, pathology, co-morbidities, history of ED, history of urinary and rectal problems, and demographic characteristics.

·      The RP-only group was most likely to be stage T2, lower Gleason score, older at diagnosis, co-morbidities, no ADT, and a history of GI problems.

·      The aRT group was most likely to be stage T3b, high Gleason score, and have had laparoscopic/robotic surgery.

·      The sRT group was most likely to be younger, have no co-morbidities, diagnosed more years ago, have had open surgery, and ADT.

These differences illustrate the first difficulty in this type of analysis: how do the differences among the patient groups before treatment affect how they will respond to treatment? Some researchers in other studies get around this problem by finding matched pairs of patients selected randomly within certain constraints. In this study, the researchers used two different techniques: “propensity score matching” and a “Cox proportional hazards model.” Propensity score matching attempts to compensate, after the fact, for those factors that seem to be correlated with the treatment decision. After “compensating,” the researchers took note of the Medicare claims for procedures, and recorded diagnoses of side effects as some patients progressed from “RP only” to “aRT” or “sRT.”

This raises another problem with this kind of analysis: the diagnoses and side effects were not necessarily related to the treatment the patient had. For example, a patient who had a colonoscopy a year after his salvage radiation, and perhaps had pre-cancerous polyps removed, is recorded as having a “gastrointestinal diagnosis” and a “gastrointestinal procedure” even though they probably had little relation to his treatment.

The other major shortcoming is that there is also no possibility of investigating how serious the side effects were. For example, urinary incontinence treated with an artificial urinary sphincter carries the same diagnosis as incontinence that only requires one pad a day. Erectile dysfunction managed with a Cialis pill is recorded the same as ED  that only responds to tri-mix injections.

So, for what it’s worth, the authors found the following:

Erectile Dysfunction (ED)

The authors note that rates of ED were high in all three groups, and most men who received post-surgery RT had erectile dysfunction prior to RT. Because of the limitations of the database, we can’t determine the seriousness or causes of the ED complications.

Gastrointestinal (GI)

There were many gastrointestinal procedures. There were more GI events among those who were treated with radiation vs. those who were not. Inexplicably, aRT was associated with lower rates of GI events than sRT. This, again, makes me suspicious that what is observed is an artifact of the methodology rather than a real effect.

Genitourinary (GU)

Men who had radiation were more likely to be diagnosed with incontinence and other urinary side effects than men who had no radiation. But earlier radiation treatment was not associated with worse effects than later treatments. Was this because patients were selected for earlier treatment had early signs of GU recovery after surgery?

Showalter et al. also conducted a similar analysis of an Italian database. They also found that radiation after prostatectomy was associated with worse GI and GU outcomes, but found that outcomes did not improve by waiting longer before radiation treatment.

Because of database limitations, it is extremely difficult to draw meaningful conclusions from these studies. There is no way to judge how serious any of the effects were, or if they were even related to treatment.

Dr. Zelefsky, apparently in agreement with Dr. D’Amico, in a Medscape opinion piece states:

“these two studies provide further confidence that earlier treatment should not increase the risk of treatment-related toxicities.”

While I agree that most of the healing of cut tissues from the surgery that will take place has already occurred within a few months, I don’t believe the data in these studies support their conclusions. Until we get better data from randomized clinical trials, how soon to treat with radiation, if at all, remains a difficult decision for both patient and doctor, with no easy answers.

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 article) reported comparable figures on erectile function at two 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%, 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 their study.

Percent of men with functional erections after 2 years

Age	RP	EBRT	BT
<50	55	100*	75*
50-59	43	52	67
60-69	27	39	44
70+	8*	30	24
Total	35	37	43
Median Age	60 years	70 years	66 years

* small sample size

Although the potency doesn’t seem to vary much between treatments in total (range 35% to 43%), 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 two 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 60-75 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). After 7 years, potency was about 67% 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 treated between at the British Columbia Cancer Agency between 1989-2012.

• ·      The men were categorized at the baseline visit by their doctors as having full (79%), partial (8%) or no (13%) erectile function. The men were re-categorized on follow-up visits by their doctors.
• ·      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).
• ·      44% had adjuvant ADT. It 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 median age was 66 at treatment.
• ·      33% had hypertension, 10% had diabetes.
• ·      Expected erectile function by age without treatment was predicted in two ways:

o   1. The Massachusetts Male Aging Study (MMAS) predicts annual impotence rates of:

§  12.4 cases per 1000 for men 40-49

§  29.8 cases per 1000 for men 50-59

§  46.4 cases per 1000 for men 60-69

§  These were estimated in 5-year increments.

o   2. 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:

o   EF loss of 25-35% if they had no ADT. The authors attribute this to trauma and psychological factors rather than dose to erectile vasculature and structures.

o   EF loss of 80-85% 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% were fully potent at 5 years and an additional 10% were partially potent.
• ·      Among men fully potent at baseline, about 40% were fully potent at 7 years and an additional 15% were partially potent.
• ·      The following table shows potency by age group after 7 years.

Age Group	Percent with full EF after 7 years
<55	80
55-59	76
60-64	53
65-69	41
70-74	22
>74	13

• ·      About 30% 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.

Age group at 5 years post BT	EF loss* due to BT+age (percent)	EF loss due to age (avg expected)†	Loss due to age as% of total loss
<60	22	13	59
60-64	38	18	47
65-69	58	26	45
70-74	75	40	53
>74	93	55	59

* among those with normal EF at baseline

† average of MMAS and 5-year older EF in study cohort at baseline

• ·      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: beta blockers, testosterone supplementation, ADT, opiates, adrenergics, etc.
• ·      Smoking
• ·      Substance abuse
• ·      Obesity
• ·      Married/sex partner

I am hopeful that someday clinicians will arrive at a consensus about collected 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.

note: Thanks to 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 me.