By: Dan Sperling, MD

Results from a randomized, controlled apples-to-apples comparison between proton beam therapy and IMRT (intensity-modulated radiation therapy) reveal that there is no treatment advantage with proton beam. The study was done with lung cancer patients, but it has serious implications for prostate cancer treatment. Two esteemed medical institutions, Massachusetts General Hospital Cancer Center and M.D. Anderson, collaborated in the study. It concluded that “proton therapy does not improve treatment failure rates or overall survival.”[i] In a similar comparison, researchers from UNC/Chapel Hill found that IMRT was as effective as proton beam in treating prostate cancer, but less expensive.[ii]

With regard to side effects, an earlier study from the University of Pennsylvania[iii] is equally crushing. It compared the side effect rates between proton beam and IMRT in treating prostate cancer. The study found no significant difference the two, since the short term occurrence of genitourinary and gastrointestinal damage was the same. Long term data is still lacking.

Both of these studies deflate expectations of a treatment that is valuable for some cancers, but is overpriced and offers no real advantage for prostate cancer.

Background

Since the proton beam therapy center at Loma Linda University opened its doors in 1990, hopes began running high in the prostate cancer community. Proton beam was hailed as a superior radiation therapy that would have high cure rates with minimal side effects. Unlike conventional radiation that uses high energy photon beams from a radioactive source, proton beam uses subatomic particles. An accelerator is needed to separate protons from atoms and fire them at the target tumor at 93,000 miles per second. “These charged particles deliver a very high dose of radiation to the cancer but release very little radiation to the normal tissue in their path.  In theory, this approach minimizes damage to healthy organs and structures…”[iv]

Proton beam therapy has shown success in the treatment of tumors in the brain, head, neck, eye and central nervous system. For children’s cancers, it may help to avoid damage to developing structures that would be affected by photon-based radiation. However, many of these cancers are relatively rare when compared to the 220,000 men who are diagnosed annually with prostate cancer. Proton beam is promoted to this large population as a highly effective treatment with fewer side effect risks. In fact, there has been a surge in the number of prostate cancer patients who seek this treatment. A recent study reports a “67% increase in the number of cases of proton treatment for prostate cancer billed to Medicare between 2006 and 2009.”[v] From an economics viewpoint, this is good news for proton beam centers, since constructing the special facilities and equipping them with a nuclear accelerator center runs up to $225 million. But from the clinical side, is it equally good news for the patients?

Controversy has arisen over whether proton beam has a sufficient track record to justify its high price. Medicare pays about $19,000 conventional radiation therapy for prostate cancer, but it pays nearly double for proton therapy – more than $32,000.  Many insurance companies now resist covering the high cost of proton beam for prostate cancer because published prostate cancer data has simply not demonstrated that it has significant merit over other forms of radiation, including Intensity-Modulated Radiation Therapy (IMRT). Why pay more when current treatments work as well, especially if proton beam’s toxicity is pretty much the same?

Less expensive forms of radiation are accepted as a standard of care for prostate cancer, especially for men who can’t have or don’t want surgery. Many patients are not told clearly that radiation does not immediately kill cancer cells. Instead, it gradually breaks down cancer’s DNA so it cannot effectively reproduce itself. This is why so many treatment sessions are needed for beam radiation, and why seed implants are permanently placed. The pressure of radiation on the cancer takes time to take effect as cells gradually die off. Cancer is less hardy than normal cells, which are not quite as affected by radiation, but the scatter effect of radiation does some damage to nearby healthy cells. This is what causes radiation-related damage to urinary, sexual and bowel function, and creates susceptibility to future secondary cancers such as bladder cancer. Finally, imaging during radiation is not done to track its effectiveness, because there is no immediate tumor destruction – so it’s impossible to know exactly what is being treated.

Contrast radiation with ablation (immediate tumor destruction) using extreme heat or cold. Ablation is an outpatient, single-time treatment that is at least as effective as radiation. Also, ablation can be done as a targeted treatment that destroys the tumor while sparing healthy tissue. For example, focal laser ablation is done under MRI guidance so the effects of treatment can be seen in real time, without damage to nearby urinary and sexual structures. It creates a high temperature that envelops the tumor and obliterates it. Immediately following treatment, the destruction is verified on MRI. Recovery is quick, and cancer control is highly effective.

Proton beam for prostate cancer implies similar advantages, but the evidence is far from compelling. The outspoken urologist Gerald Chodak, MD did not mince words about this:

For those wanting some specific facts about the results, here is what we know. …[T]he longest follow-up available has been from California but they only reported PSA failure rates at seven years without any information about long-term survival.  Using PSA as a surrogate for success is not an acceptable measure and it can deliver incorrect conclusions.  So, at this time, we do not know how well it works long-term…

The bottom line, for now, is to be aware of the limitations that exist for PBT [proton beam therapy], rather than be swayed by the theoretical hype and extensive marketing.   If studies can actually prove it has advantages then it may be worth the higher cost; but until that occurs, it makes no sense to pay more for a treatment that offers no proven advantages over conventional radiation.[vi]

Dr. Chodak is specifically calling for randomized, controlled comparison studies in prostate cancer like the lung cancer study mentioned at the opening of this article. The trouble is that such studies are expensive, and given the bottom line costs of proton beam (and less so IMRT, but still expensive) it may be years before a large enough trial can be implemented, completed and analyzed. Add another 10 years to that for substantial long-term data as patients are followed after treatment.

The lung cancer study had 255 patients who were well matched and randomly assigned to either proton beam or IMRT. They were tracked for 12 months for evidence of recurrence. The study was well-designed and professionally conducted. For those who have been champions of proton beam, their hopes must have been deflated by the failure of proton beam to demonstrate significant advantages.

Prostate cancer patients who are on the threshold of making a treatment decision have the task of investigating each option. Treatments that offer immediate, verifiable results like image-guided focal laser ablation must be weighed against the mysterious processes and long term vulnerabilities associated with all forms of radiation. Regarding proton beam, it is clearly important to get past the marketing to the heart of the matter. It is a treatment with a steep price tag and no proven advantage, and is being oversold for treating prostate cancer. Until long term success and side effect data are generated, it appears that in the short term it is a pricey disappointment.

[i] Mulcahy, Nick. “Finally, RTC Results for Proton Therapy in a Cancer.” Medscape Medical News. June 21, 2016. http://www.medscape.com/viewarticle/865137#vp_1

[ii] Sheets N et al. Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer. JAMA. 2012 Apr 18;307(15):1611-20.

[iii] Fang P, Mick R, Deville C et al. A case-matched study of toxicity outcomes after proton therapy and intensity-modulated radiation therapy for prostate cancer.  Cancer. 2014 Nov 25. doi: 10.1002/cncr.29148. [Epub ahead of print]

[iv]Brooks, Durado. Is proton beam therapy for prostate cancer worth the cost? Posted Feb. 20, 2013 at http://blogs.cancer.org/expertvoices/2013/02/20/is-proton-beam-therapy-for-prostate-cancer-worth-the-cost/

[v] Ibid.

[vi] http://www.everydayhealth.com/columns/gerald-chodak-the-prostate-cancer-doc/proton-beam-radiation-prostate-cancer-worth-the-cost/