First directly comparative data question safety of PBRT vs. IMRT

For the first time, some 15 years after proton beam radiation therapy (PBRT) was initially popularized as a potential treatment for prostate cancer by the group at Loma Linda, we have an independent assessment of the risk for side effects associated with this form of radiation therapy … and the comparative data are not good.

Sheets et al. will be presenting these data tomorrow at the Genitourinary Cancer Symposium in San Francisco, but the American Society for Clincial Oncology (ASCO) has already issued a media release, and the abstract of  the presentation is available on line.

The study by Sheets et al. also compared outcomes of traditional (three-dimensional, conformal) external beam radiation therapy (3D-CRT) to intensity-modulated radiation therapy (IMRT). Data from the study suggest that IMRT is more effective than 3D-CRT — although there are indications that IMRT is associated with a greater risk for sexual dysfunction post-treatment (probably because it can be carried out with higher levels of total radiation dose for greater efficacy).

The research team, under the leadership of Dr. Chen at the University of North Carolina, Chapel Hill, carried out a careful study of Medicare records from > 12,000 men treated for non-metastatic prostate cancer between 2000 and 2009. Follow-up data was available on patients for an average of about 4 years.

The results of the study (shown in terms of “propensity scores”) are as follows:

  • Use of intensity-modulated radiation therapy (IMRT) increased from 0.15 percent in 2000 to 95.9 percent in 2008.
  • Men treated with IMRT as opposed to 3D-CRT were
    • Less likely to be diagnosed with gastrointestinal morbidity (13.4 vs. 14.7 per 100 person-years, p < 0.001)
    • Less likely to have subsequent hip fractures (0.8 vs. 1.0 per 100 person-years, p = 0.006)
    • More likely to be diagnosed with erectile dysfunction (5.9 vs. 5.3 per 100 person-years, p = 0.006).
    • Less likely to need additional cancer therapy (2.5 vs. 3.1 per 100 person-years, p < 0.001).
  • Men treated with PBRT as opposed to IMRT (between 2002 and 2007) were
    • More likely to be diagnosed with gastrointestinal morbidity (17.8 vs. 12.2 per 100 person-years, p < 0.001).
    • Equally likely to have other complications and side effects
    • Equally likely to need additional cancer therapy

The study suggests that patients treated with PBRT had about a 30 percent greater likelihood of bowel problems, such as bleeding and blockages, than similar men given IMRT. This result is in complete contrast to claims from some of the PBRT centers (and their “boosters”) that PBRT is associated with a lower risk for complications than other forms of radiation therapy.

The results of this study by Chen and his colleagues adds compelling evidence in support of the argument (supported by The “New” Prostate Cancer InfoLink) that some form of independent, well-designed study is needed to compare the outcomes of well-characterized patients treated with PBRT as opposed to IGRT/IMRT — and perhaps stereotactic body radiation therapy (SBRT) too. It does need to be recognized that this type of study, based on Medicare records, is fraught with all sorts of limitations, but it is clear, finally, that the advocates for PBRT as being “safer” than other modern forms of radiation therapy for the treatment of localized prostate cancer are no longer standing on anything approaching solid ground. (It has long been accepted that PBRT was likely to be superior to the much older 3D-CRT.)

According to Dr. Chen, quoted in a report in The Boston Globe, “There’s no clear evidence that proton therapy is better’’ for prostate cancer. He went on to add that  “We found that patients who were treated with IMRT required fewer additional treatments after radiation which indicates better cancer control.’’

8 Responses

  1. Although this information might be well intended, a comparative study of all optional prostate cancer treatments (TURP, TUIP, TULIP, BALDI, LP, MIC-HYP, VLAP, TUNA, cyrotherapy, robot-assisted surgery, PBRT, watching and waiting) should be done using the same source of Medicare data so that patients can make an informed decision as to which could be a potential option. Many studies will be done and have been done concerning which is best for the patient, according to the medical profession. It still comes down to the choice of the patient. This study reads of being biased rather than unbiased.

  2. Dear Mr. Sims:

    Several of the treatments you refer to (e.g., TUIP, TULIP, LP, VLAP, and TUNA) are not, in fact, appropriate treatments for prostate cancer at all. These treatments are only appropriate for the management of benign prostatic hyperplasia (BPH), which is a quite different disorder. In addition, I am not familiar with either BALDI or MYC-HYP, so I cannot comment on them specifically, but I have never heard of their use in the first-line treatment of prostate cancer.

  3. Regardless what may or may not be appropriate for prostate cancer treatments, until all studies take into account the Medicare data and all treatments are compared, none of the studies can be used for a patient’s decision.

  4. Dear Norvil:

    It is not a perfect world. Patients need to be able to make their decisions based on the data that actually is available. Analysis of Medicare data that do not necessarily include all the relevant clinical facts (which is the case with all the Medicare data) will not resolve that problem. What is more, if we wait 20 years to conduct a full scale, prospective trial of “all treatments,” several of those treatments will be out of use (for any one of many possible reasons) long before we get the results.

  5. This is interesting, almost the opposite of what I would have expected, given the electromagnetic theory that I know in detail. My expectation was that PBRT would have fewer gastrointestinal side-effects than any form of EBRT. By “fewer” I mean sorts of side-effects and absolute numbers available so far. My reasoning was that the protons could be rather exactly directed (as a “pencil”) to a low-area region, whereas electromagnetic radiation of any wavelength spreads in a cone whose cross-section grows with distance from the source. This growth can damage organs and tissue outside the target. So is there any physical and/or physiological explanation available for this (to me) counterintuitive, compelling evidence?

  6. Dear George:

    I can think of one very simple one … Radiation does not travel is straight lines or cones through human tissues. It bounces off some of these tissues and is refracted by others. So the actual radiation is scattered somewhat unpredictably by the tissues it passes through. Also, since protons are significantly larger that photons, it may be that they are more susceptible to such effects. But what do I know? I am not a radiation physicist!

  7. I don’t know either, but it does seem strange. You might well be right about the photon scattering, but the effects that cause proton scattering might (I don’t know) be different from those that cause photon scattering. Whatever the causes, this came as a surprise to me.

  8. Like many other men who have had proton radiation for prostate cancer I have had no side effects from my treatment almost 3 years ago. I can’t say the same for other friends who chose either surgery or photon radiation. After reading many of the anecdotes on YANA I am very thankful for the informed choice that I made. Survival rates of 5-10 years were about the same, but the side effects were always the difference. Read some of the proton stories on YANA and then read many of the others. It is truly striking. I don’t know if I would trust CPT codes from Medicare and make that the cornerstone of my study.

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