Quality of life after three different first-line radiation therapies for localized disease: Part 1

Some of the leading lights in radiation oncology have collaborated on a study (by Evans et al.) of patient-reported quality of life (QOL) following various primary radiation treatments for prostate cancer. They analyzed three monotherapies (all without androgen deprivation therapy [ADT]):

  • Low-dose-rate brachytherapy (LDRBT)
  • Intensity-modulated radiation therapy (IMRT), and
  • Stereotactic body radiation therapy (SBRT)

They did not include high-dose-rate brachytherapy or proton therapy.

Because this study was so far-reaching in its scope and its findings, it is worth taking a close, detailed look at it. We have therefore broken this report into three parts. In Part 1, immediately below, we’ll look at the basis of the study – how the study was designed and carried out, and what it purports to tell us. In Part 2, we will look at some of the more important findings of the study. And in Part 3, we will discuss the implications and caveats of its findings, and draw conclusions.


The purpose of the study was to evaluate three primary radiation therapies — LDRBT, IMRT and SBRT — with respect to the patient-perceived side effects of those treatments, and to do so in a standardized and consistent manner. While this was a prospective study, it was not a randomized comparison, which is the gold standard for doing that. However, it does provide the doctor and the patient with more information on what they can reasonably expect, across those treatments, than we’ve ever had before.

Data was contributed by several of the top institutions in the US. My best guess at who supplied which data is as follows. I also show the number of patients in the two-year follow up:

  • LDRBT: Cleveland Clinic (243 patients)
  • IMRT: University of Michigan, Michigan State University, Washington University, Cedars-Sinai, M. D. Anderson Cancer Center, Massachusetts General Hospital (140 patients)
  • SBRT: Beth Israel Deaconess Hospital, Georgetown University, 21st Century Oncology/Fort Myers (272 patients)

I don’t know how they selected which doctors and medical centers to include. In addition, the study was done with the assistance of the PROSTQA Study Consortium, a blue-ribbon panel of top researchers. As such, their results are a good indicator of outcomes from top practitioners at major treatment centers, and are not necessarily a good indicator of expected outcomes in community practice. I’m sure that many patients have favorite doctors whose work was not represented in this study, and they will argue that these results are not representative.

Because this was not set up as a randomized comparison of treatments, differences in patient selection may skew the results. Importantly, the LDRBT cohort is 5 years younger (65 years, median) than the other two groups (69 years, median). In all quality-of-life studies, younger patients do better. They are less likely to suffer deleterious effects of radiation, and they are more resilient in their recovery. Paralleling the difference in age at baseline, the baseline sexual QOL was best for LDRBT, and the baseline prostate symptom scores were best for LDRBT, followed by IMRT and SBRT.

The instruments they used to evaluate quality of life were EPIC-26 and SF-12. Patient-reported assessments have an advantage over physician-reported toxicity reports. The physician data depends on the patient to voluntarily tell the doctor about all adverse events, which is useful for higher grade events (3 or 4), but is less reliable for lower grade events (1 or 2) that the patient might never bring to the doctor’s attention. Some men “tough it out;” some see their primary care physician instead (who may be more accessible); and some worry about even the most minor events. The survey instruments used here are standardized and validated, and guide the patient through a detailed assessment of the QOL issues that have been found to matter most. Patients filled them out at baseline, at 1-2 months, 6, 12, and 24 months. EPIC scores are based on scale of 0 (worst) to 100 (best). Although they also measured such qualities as general physical and mental status, and vitality/well-being, none of these were impacted by treatments.

IMRT and LDRBT patients were treated from 2003 to 2006; SBRT patients from 2007 to 2011. Contemporary best practice was observed as follows:

  • LDRBT: 144 Gy prescribed dose for I-125, US-guided, transperineal placement, I-125 or Pd-103 used, and 3-5 mm margins (more details here)
  • IMRT:76-79 Gy in 1.8-2.0 Gy increments, and 0.5-1.5 cm margins.
  • SBRT: 35-40 Gy in 5 fractions, fiducials or Calypso image guidance, and 3-5 mm margins.

There were two kinds of urinary problems that were measured: urinary incontinence (leakage, dribbling, control, and pad use) and urinary irritation/obstruction (frequency, pain/burning, weak/incomplete). Bowel issues comprised urgency, frequency, leakage, bleeding, and pain. The sexual domain comprised ability to have erections, their firmness, and frequency when needed; also, quality of orgasms and overall sexual function.

All of the study’s findings relate to how much patient evaluations changed compared to their baseline evaluations in the urinary, rectal, and sexual quality of life domains. We expect that the radiation therapies that do the least damage will show the least deterioration in the patient perceptions in each domain.

Because the study was not randomized, and it did not attempt to match triplets of patients on their demographics and co-morbidities, we have the difficulty of comparing results in different kinds of patients. The analysis of patient characteristics across treatments revealed only one real glaring discrepancy — LDRBT patients were 5 years younger than the rest. The authors made some attempt to restore comparability by only looking at sexual scores among patients who were 60 years of age or older, but such analyses were limited in their published results. In my opinion, they ought to have computed age-adjusted scores in all domains. The failure to do so will compound the difficulties in interpreting results as they carry their tracking into the future when the aging of the study population has greater effects.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel, who was treated with SBRT in 2010. Part 2 of this report will be made available tomorrow (Wednesday, August 26, 2015) and Part 3 on Thursday.

One Response

  1. Correction: As I said above, the study did not specify which institutions were involved, and I just guessed based on the authors involved. I wrote to Daniel Hamstra, the corresponding author of the study. He informed me that the LDRBT patients did not all come from Cleveland Clinic, but were spread out over all the institutions that offer it. Here’s his clarification:

    “LDR or IMRT
    Michigan (2 sites)
    Mass General
    Beth Israel Deaconess
    MD Anderson
    Cleveland Clinic
    Washington University (St Louis)

    21st Century (2 sites)

    Cedars Sinai and Michigan state did not treat any patients. They were just involved in analysis.

    No SBRT patients from Beth Israel are represented here. But Irving Kaplan certainly has done some cyberknife

    The LDR/IMRT data is the same as

    Quality of life and satisfaction with outcome among prostate-cancer survivors.

    Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, Lin X, Greenfield TK, Litwin MS, Saigal CS, Mahadevan A, Klein E, Kibel A, Pisters LL, Kuban D, Kaplan I, Wood D, Ciezki J, Shah N, Wei JT.”

    We also had a very interesting and enlightening back and forth about the conclusions I drew from the study. I will append those comments to Part 3.

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