Adverse events of primary, intensity-modulated radiation therapy (IMRT)

In a recent commentary, the Sitemaster mentioned some common adverse effects of radical prostatectomy, some of which (e.g., perceived penile shrinkage, climacturia) 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 therapy, below is a list of such effects, ranked by approximate incidence, for primary IMRT.

This list only applies to primary or first-line treatment with IMRT and not to salvage treatments, which may have a very different side effect profile. Also, these data are not purely for IMRT — they include some patients treated with primary 3D-conformal radiation therapy (3D-CRT) as well. Furthermore, 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 these data necessarily apply to either stereotactic body radiation therapy (SBRT) or any form of brachytherapy.

Most of the data on acute side effects are pulled from the Sanda et al. study, which represents patient-reported outcomes from nine of the top US academic institutions at up to 2 years of follow-up, and is not necessarily indicative of community practice. Most of the later-term side effect data are given as their absolute incidence (a number at a particular time after treatment). Some side effects are given as increases over baseline function (indicated by “+” symbol). Unless otherwise specified, these are also 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 co-morbidities. 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 (at 5 years): 89 percent
  • Fatigue: 32 percent
  • Sexual function as a big/moderate problem (at 1 year): 31 percent
  • Frequent urination: +18 percent
  • Vitality/hormonal function as a big/moderate problem (at 1 year): 18 percent
  • Bowel urgency: +15 percent
  • Bowel frequency: +14 percent
  • Urinary irritation or obstruction as a big/moderate problem (at 1 year): 14 percent
  • Bowel/rectal function as a big/moderate problem (at 1 year): 11 percent
  • Dysuria (pain while urinating): +11 percent
  • Weak stream: +10 percent
  • Leaking of urine  > 1× per day: +9 percent
  • Rectal pain: +5 percent
  • Fecal incontinence: +5 percent
  • Dribbling of urine: +4 percent
  • Urinary incontinence as a big/moderate problem (at 1 year): 4 percent
  • Any pad use: +3 percent
  • Bloody stools: +2 percent

Other rare effects with an  <1% incidence of < 1 percent include: rectourethral fistula, bladder neck contracture requiring surgical intervention, and second primary pelvic cancers.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

Sources for this commentary:

8 Responses

  1. Thank you, Allen, for another excellent commentary. The radiation oncologist I consulted at MSKCC wanted to treat me “aggressively” and combine IMRT with HDR brachytherapy. I imagine this would include an entire additional list of safety issues. I was also told that such treatment offered a “10 to 20% chance of cure” for my Gleason 9 (4 + 5) locally advanced prostate cancer. I was very doubtful of this claim, especially since my med/onc flatly stated I was not curable and I believe this is the more widely accepted position, given my numbers. Would you agree?



  2. I agree that these adverse effects are only mentioned in general terms by the urologist (like urinary dysfunction, sexual dysfunction, or bowel dysfunction) — whether they are not aware of the details or don’t want to know them.

    During my regular check-ups (after IMRT and adjuvant ADT) I keep my urologist informed about my symptoms (i.e., loss of erections, semen, and sexual function; light fecal incontinence) but until now that did not lead to any further treatment or medication.

    I found the American Cancer Society’s “prostate cancer survivorship guidelines” to be a great help in identifying my problems. Here in The Netherlands we don’t have such a comprehensive patient information guide.

  3. Allen,

    I’ll add my thanks for this article. I was especially encouraged by the statement that new side effects rarely emerge after 2 years.

    Regarding urinary side effects, the IMRT (TomoTherapy) I had in March and April of 2013 has actually had a beneficial effect for me. For many years I would get up three times at night to urinate. Now, I rarely get up more than twice, more than half the time just once, and occasionally not at all. A scan to place fiducials before treatment identified an enlarged area in the central zone, and I’m thinking the radiation knocked that out, thereby decreasing sensitivity to urinary pressure — just my layman’s hunch.

  4. Len,

    I don’t know enough of the details of your case to comment, and I’m not a doctor. Whether your cancer is curable or not comes down to a question about whether it has only progressed locally, or whether there are distant metastases or systemic micrometastases. A bone scan and CT are usually the first diagnostic tools to detect distant metastases. Newer PET scans can detect smaller metastases, but there are no good tests for systemic micrometastases — that involves some guesswork. High and very rapidly increasing PSA, high volume cancer, and clinical stage cT3/T4 are typical indicators, but there is no certainty.

    Your doctor at MSKCC is certainly correct that, in high-risk cases, IMRT with a brachy boost has the best documented success rate, at least in terms of biochemical progression-free survival (see this link). You are correct that there is a cost in terms of side effects to such combined modality treatment. There have been some clinical trials of HDR brachy or SBRT monotherapy in an effort to reduce the side effect profile while maintaining oncological control.

    There are no objective answers. It’s up to you and your doctors to decide whether you are willing to take a chance at permanent cancer control at the expense of increased side effects of treatment.

  5. Antoniken,

    To aid me and my doctor in assessing my symptoms, I fill out a few forms periodically. Because I filled them out at baseline and periodically post-treatment, I am able to assess any deterioration or improvement. The forms I use are these:

    • EPIC —
    • SHIM —
    • IPSS —

  6. Jim:

    It is very common for urinary symptoms to eventually improve to better than baseline after primary RT. The typical pattern is a short-term worsening during the acute inflammatory phase, followed by slow improvement as excess tissue is reduced.

  7. Thanks Allen for the forms; I am familiar with forms EPIC-CP, SHIM/HEF-5, but in a somewhat shorter edition.

  8. @AntonikenL

    You are right. I am a Dutch citizen who got no information. Just a childish drawing and a *command* to choose radiotherapy or radical prostectomy, at the VUMC. I was told that I was not eligible for brachytherapy “as your prostate is too large.” I have aggressive prostate cancer and am familiar with staging. I would probably be dead by now if I had not left for Sweden, where I got an advanced treatment. I will never return. This is a complex story. Suffice it to say that the Guideline (Richtlijn) and Oncoline were biased to omit information, and in one sense remain so, as far as treatment options go.

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