Proton Therapy: worth the cost, or is it just for Bragging rights?

Disclaimer: This essay was originally written for the BMED 7004 course I took last fall. It has been lightly edited for use on this blog.

Just a couple streets away Emory University Hospital Midtown is a large construction site, taking up an entire city block right in the middle of midtown. Construction has been going on for over two years, and we can finally see the progress as the main structure of the building goes up. It is prime real estate, and the cost of this vast project is equally high. For the sweet cost of $200 million dollars, Emory University will be one of the few hospitals in the country to have a proton therapy center. Currently, however, the building lies empty for want of further funds.

Since the first proton therapy center opened in 1990, the technology has been touted as the future of radiation therapy [1]. It promises to hit cancer cells harder while simultaneously minimizing side effects for patients – the “holy grail” of cancer treatment. Though traditional radiation therapy techniques is effective in targeting the rapidly dividing cells of a tumor, there are many unpleasant side effects to innocent bystander tissues. Skin is always hit by collateral radiation, creating scarring and damage resembling burns. But proton therapy promises something better. The concept is straightforward: rather than using ionized electromagnetic radiation to target tumors (i.e. photon therapy), proton therapy uses massive ionized protons. The theoretical benefit is that unlike EM waves, which will deposit some of their energy to all tissue in their up to the tumor, protons would release far less energy up until the point they hit their target. (This is due to the sharp nature of the so-called “Bragg peak” of the energy distribution of protons, and in this ethics paper is used largely for a titular pun). The benefits could be astounding in terms of reducing the common and debilitating side effects of radiation therapy, and could potentially improve survival outcomes of patients [2]. Patient groups were thrilled by these possibilities.

With all these theoretical benefits, one would expect that there would have been many more than 8 centers in the country after twenty-five years. But it doesn’t seem to have taken off that way. Recently, Hampton university announced that it had missed its predicted patient load – treating less than 30% of what was expected [3]. So is proton therapy really useful, or just a solution in search of a problem?

The emerging technology committee of ASTRO, the national professional association for radiation oncology, sought to answer this and other questions. Specifically: “is proton therapy better than the current standard of care?” and “should it be adopted as the standard of care?” These two questions, while similar enough when asking the NIH for research funds, pose fundamentally different questions in terms of the ethics of treating patients with cancer. The science already shows that proton therapy is, objectively, “better” than photon therapy in terms of reducing collateral damage and allowing for increasing doses to the malignant regions of tissue. But its clinical use has not proven its sufficient value to replace the current standard of care.

Defining clinical value is not an easy task, especially when it comes to the care of patients with cancer. There are multiple stakeholders to consider – patients, physicians, researchers, and the hospital and financial investors who make treatments possible in the first place.

In an idealistic world, one could argue the most important stakeholder is the patient. She is the one suffering from the disease and facing potential mortality. And while the responsibilities of the other stakeholders arguably end at the completion of treatment, she is the one who will deal with the consequences for the rest of her life. The ASTRO review shows that the data support the improvements of proton therapy in many organ systems. In the case of head and neck tumors, for example, proton therapy is apt for avoiding radiation dosage to the very sensitive central nervous system. Likewise for prostate cancer, which has the largest number of patients recorded receiving proton therapy, where dose escalation to the tumor has been successfully done without increasing toxicity to healthy tissue. However, for nearly all of these studies, the conclusion drawn is that more comparative studies are needed. For our patient, given the choice of two therapies with no evidence-based difference in outcome but with one having even just the potential of fewer side effects, it’s natural that she would go with that one. And in our healthcare system, the cost to her is the same; the sheer financial burden of any cancer diagnosis has already maxed out what a patient could pay out of pocket. Proton therapy is, in almost all cases, more expensive than traditional photon therapy. But with fixed co-pays or deductibles, the benefit/cost ratio can only go up by presenting the opportunity of a better quality of life post-treatment.

The value equation is clearly skewed the other way for the insurers who are financially responsible for the treatment decision. They would prefer to produce the same outcome at lesser cost. The WSJ journal article quotes a 66% increase in cost for proton therapy for prostate cancer compared to traditional therapy. Therefore it’s completely understandable that many insurers stopped reimbursing for protons; they have a fiduciary responsibility to not distribute their limited resources for little to no gain in outcomes. It’s a zero-sum game, and proton therapy here is the loser.

While ethical concerns for many other clinical treatments are often limited to the financially-focused stakeholders, in the case of a brand new and untested field like proton therapy, the researchers and physicians performing these clinical trials have a huge stake in the situation. With rare exceptions, the only data we have for proton therapy comes from government and privately funded clinical trials. The academic and industry-based researchers naturally are invested in the success of their trials. A statistically significant survival outcome in a large trial is the watershed moment that could propel the field of proton therapy into the clinical mainstream. Being an author on this hypothetical paper could make a career. In light of this conflict, it’s interesting to note that the literature on past clinical trials never say that proton therapy is “not worth it”. Rather, the conclusions drawn are that “more studies are needed.” If indeed it turns out that proton therapy is not substantially more valuable than the standard of care, how many billions of dollars will need to be spent first?

Some researchers and physicians would argue quite the opposite. That in fact, millions of dollars are being wasted on clinical trials when the science has already shown that proton therapy is superior to traditional therapy. A 2007 article from a group at Harvard / Mass General concluded (emphasis added):

“Our assessment is that there is no medical rationale for clinical trials of protons as they deliver lower biologically effective doses to non-target tissue than do photons for a specified dose and dose distribution to the target. […] Were proton therapy less expensive than X-ray therapy, there would be no interest in conducting phase III trails. The talent, effort and funds required to conduct phase III clinical trials of protons vs photons would surely be more productive in the advancement of radiation oncology if employed to investigate real problems.” [4]

The authors claim that the money used for funding proton therapy clinical trials would be better spent elsewhere. They ask what conclusions can be drawn from such trials, and the point is well considered. If the main advantage of proton therapy is that it produces better quality of life for patients, how could we even quantify that for research purposes? Secondly, they advise that there is no medical rationale for these trials. Our modern approach to medicine, while attempting to become more evidence based, still holds on to the principal that the doctor knows best. Doctors are allowed to prescribe drugs for off-label uses, and can recommend a particular type of therapy if they deem it to be better for the patient. And many physicians would, all other things equal, prescribe proton therapy even if the quantified survival outcomes are the same as traditional therapy; the potential of a better quality of life is likely to be worth it. Unfortunately, what this viewpoint and what these authors don’t consider is the financial cost of not only building proton therapy infrastructure, but also the increased cost of each proton therapy treatment.

And so finally, we must consider the motivations of the healthcare entities that finance the massive cost of developing a proton therapy center. The hundreds of millions of dollars for construction alone rivals the entire operating budget of many hospitals. Consider how that money could be spent: a course of traditional radiation costs $8,000 – $18,000 [5]; the construction cost of Emory’s proton center could instead be used to treat over 10,000 patients with standard therapy pro bono. But of course it’s not all about the finances. There is prestige associated with being on the avant-garde of treatments. This is evident by looking at the prestigious list of hospitals which currently have or are building proton therapy centers: Johns Hopkins, the Mayo Clinic, MD Anderson, Massachusetts General Hospital, the University of Pennsylvania, etc. All highly renowned hospitals with nationally-recognized cancer centers. In fact, the press release for the announcement of the Emory center stated:

“The center bolsters the position of Winship Cancer Institute […] as the state’s leader in cancer treatment.” [6]

This is not to say that the main motivation, or even a significant portion of it, is because of pride or prestige. Unfortunately, for paradigm shifts in clinical care, it often is a chicken and egg problem. Determining the long term costs and benefits of a new therapy requires patient data, lots of it, and collecting that data requires the infrastructure. At the same time, it’s easy to be skeptical of the value of these large financial investments for an unproven technology. Someone has to bare the burden of being a pioneer in the field, with all the responsibilities and repercussions that come with it.

It’s not the Wild West, however, and there are both implicit and explicit contracts in place to reduce the conflicts of interest noted above. Importantly, all clinical trial outcomes are reported to the US government. So even if the published literature seemingly forgets to mention any less-than-successful outcomes, a quick search on reveals quite a few trials with a status of “Withdrawn” or “Terminated.” At least having this resource available will enable future researchers to be more efficient when planning out new treatments. One could also argue that because of the large financial burden of running a trial and limited locations to recruit and treat patients, there is an increased need for collaborations between institutions. The Emory proton center will not only be used by its host institution – there are already agreements in place for research and clinical use by Children’s Healthcare of Atlanta and Georgia Tech. And finally, we have to consider the free market forces that will also naturally balance the value propositions of each of the stakeholders. While many private entities are excited by the prospect of investing in a brand new technology, if it doesn’t live up to its promises, one can be sure that future financiers will be deterred. Similarly on the research side, there is a lot of excitement now amongst clinicians and scientists, and the NIH funding seems to be following the buzz. But the NIH is capable of pivoting funding away, due to the self-regulating nature of the peer review process.

Personally, I’m quite excited by proton therapy and the promises it holds. I’m a firm believer that the financial side of things will eventually work itself out. It’s always difficult to be first to market, while the technology is as yet unrefined and the infrastructure is not in place. It’s been the same way for every wave of healthcare technology in the past. MRI scanners, the multimillion dollar behemoths, are found at even small-scale hospitals today; twenty years ago, that would not have been the case at all. And the very nature of research is to take a risk to try and find something new; of course it will be uncharted and murky waters at first, but as soon as we find the right way to shed light on it, I think we’ll find the right use for proton therapy.


[1]      M. Beck, “Big Bets on Proton Therapy Face Uncertain Future,” The Wall Street Journal, May 26, 2015.

[2]       A. M. Allen, et. al., “An evidence based review of proton beam therapy: The report of ASTRO’s emerging technology committee,” Radiotherapy & Oncology 103 (1) p8-11 (2012)

[3]       P. Salasky, “Hampton proton therapy center treating a fraction of its predicted number of patients,” The Daily Press, October 17, 2015.

[4]       H. Suit, et. al., “Should positive phase III clinical data be required before proton beam therapy is more widely adopted? No,” Radiotherapy and Oncology 86, 148-153 (2008).

[5]       A. J. Paravati, et. al., “Variation in the Cost of Radiation Therapy Among Medicare Patients with Cancer,” J. Oncol. Practice (2015).

[6]       “Emory Proton Therapy Center begins construction,” Emory News Center, May 2, 2013.