For many years, the facility at Loma Linda in California was the only commercially functional proton beam radiation facility in the USA. Now there are five such facilities (at Loma Linda, CA; Bloomington, IN; Boston, MA; Houston, TX; and Jacksonville, FL), with three more under construction and 10 more in the planning stage. About 8,000 men have undergone proton beam radiotherapy for prostate cancer since the Loma Linda facility first opened in 1990.
There seems no doubt that proton beam radiotherapy (PBRT) is a valuable and effective method for the treatment of prostate cancer and certain other forms of cancer, but prostate cancer is the “clinical business model” on which proton beam radiotherapy has been primarily dependent. The problem is that there has never been a randomized clinical trial of PBRT as compared to standard forms of external beam radiotherapy, and building new PBRT facilities is expensive. Why would we be doing this unless there was a clear and proven clinical benefit for patients?
For a detailed discussion of this topic, see the recent article in Oncology News International. You can also cast a vote on whether you believe there should be randomized clinical trials of PBRT in prostate cancer on the CancerNetwork.com home page. The “New” Prostate Cancer InfoLink would note that without such clinical trials, no new form of hormone therapy or chemotherapy would even get approved for the treatment of prostate cancer! If PBRT really is better than standard external beam radiotherapy, then let’s find out for sure and stop wasting money on the older technology. If it isn’t, then we probably don’t need PBRT facilities all over the country!
Filed under: Management, Treatment
Nice post. I totally agree. But, like robotic surgery, it will require urologists to be willing to turn “their” patients over to the randomized trial process. There are far too few who are willing to look at prostate cancer care that way. Thus, decades after radiation therapy and surgery have been generally agreed to be equivalent, we still have leaders arguing in public like small children as to which modality is “best”.
Thank you for your comment Dr. Glode. An idealist would hope that the radiation oncology community would see the benefit of conducting such a trial. Sadly there is no reasonable hope left that we will ever see an unbiased comparison of (say) minimally invasive surgery and PBRT.
Proton therapy and prostate cancer have become inextricably linked – most patients treated with proton therapy at Loma Linda’s facility have been prostate cancer patients, for example.
Despite the theoretical dosimetric advantage of a proton beam, there are enough questions about proton delivery to justify the ethical performance of a randomized trial comparing proton to photon treatment. Concerns, or example, might include issues such as: proton beam’s sensitivity to heterogeneity of density (i.e. bone and air) with a patient’s pelvis, the widening of penumbra (i.e. beam edges become “fuzzy”) the deeper the beam penetrates, and issues with secondary neutron generation that could have implications for secondary neoplasm generation.
The RTOG and others are currently exploring a non-randomized clinical trial design that would evaluate toxic effects of IMRT and proton therapy that might provide some useful data.
As of today, there are inadequate scientific data to justify the claim that proton therapy offers a strategy with either better cure rates or fewer side effects compared with IMRT.
Thanks for the additional insights Dr. Sandler.
There is more than enough data on individuals who have completed various forms of treatment, including proton treatment, to do an analysis. How many of those are still alive and with or without side effects. Compare that statistic against those during the same time period who chose different types of treatments. As a lay person and also a PCa patient that would be all the proof necessary.
There is an obvious temptation to make comparisons of outcome from two treatments. However, comparisons of patient cohorts without adjustment for critical variables, such as tumor burden, are not a valid basis for conclusions about relative merit. For that, one needs randomized trials and appropriate multivariate statistical analysis. Dr. Sandler’s comment nicely alludes to this. It is right on target and broadly applicable.
As a struggling soon to be consumer of prostate cancer treatment it is a daunting task to settle on a choice. Proton therapy is very compelling but finding any hard facts, let alone some standardized comparison, really muddies the issue. But as long as the money flows to proton therapy there may not be any need for a scientific process. Don’t you just love Capitalism. Live long and prosper.
I had proton beam treatment for prostate cancer at Loma Linda Medical Center, 44 treatments, March 6 to May 6, 2008. I had a PSA of 20 ng/mL when I went to Loma Linda. A PSA done about July 15, 2008 was 0. I have no side effects. I would say this treatment works.
Dear Mr. Richter: I don’t think anyone is suggesting that proton beam therapy doesn’t “work.” I think the question many people would like an answer to is, “Does it work as well, or perhaps even better, than other forms of radiotherapy?”
On the subject of randomized clinical trials for proton therapy, the best answer to the question has been provided by Goiten and Cox in an article entitled “Should Randomized Clinical Trials Be Required for Proton Radiotherapy?” This article is definitive in stating that randomized trials between the various modalities and protons would be basically unethical based on the unchallenged superiority of protons. The paper also makes the point that the whole argument is driven by the fact that proton facilities are expensive and the cost of the treatment is currently greater than most other treatment modalities. I have excerpted a pertinent part of the author’s paper below:
“Of course, it is really all about money. Can anyone seriously believe that, if protons were cheaper than x-rays, there would be similar objections raised as to their immediate and widespread use? This seemingly rigorous academic discussion, in reality, is driven by the uncontested fact that protons are more expensive than x-rays.
“Although we can understand (though not necessarily agree with) the desire to rely on [randomized clinical trials (RCTs)] to establish the advantage of a superior therapy, we find it totally unacceptable to insist on what we judge to be unethical RCTs purely to establish the financial cost-effectiveness of an admittedly better technology — nor would patients, if fully informed, consent to participate in such studies.”
Fuller Jones
[Editorial comment: We have abbreviated Mr. Jones's comment somewhat for readability. The full article that Mr. Jones refers to is available if you click on the link in the text above.]
As Mr. Jones has stated elsewhere, he is a strong advocate favoring the use of proton beam radiotherapy (PBRT) in the treatment of localized prostate cancer.
The “New” Prostate Cancer InfoLink takes no specific position on the relative value of different types of radiation therapy since there are no well-founded data on which base a comparison. Our concern is only to ensure that newly diagnosed patients are able to receive unbiased information on which to make decisions about their therapeutic options.
At this time there is clearly a significant division of opinion about the value of PBRT within the radio-oncology community itself, and in our opinion the wise advocate should make that clear to any newly diagnosed patient.