Proton radiotherapy is a rapidly expanding treatment modality that has attractive dosimetric advantages compared to photon radiotherapy, albeit at an increased capital and per-fraction reimbursement costs . The main findings of this study are that worldwide, PTC websites commonly contain DTCA for PBT that are frequently not supported by evidence, and often advertise the treatment of cancer sites not currently endorsed by international consensus guidelines. This did not appear to be localized to a single centre, country or disease site; rather, this trend exists globally and for a multitude of cancer sites.
The ethical implications of DTCA within healthcare are neither new, nor unique to radiation oncology. Currently, the United States and New Zealand are the only two countries that permit print and broadcast DTCA within healthcare ; no countries regulate DTCA from online sources . In the U.S., the Food and Drug Administration (FDA) regulates print and broadcast advertising: although only major risk information must be disclosed, they must direct consumers to other accessible sources of information on literature and all other associated risks . Supporters of DTCA argue that it increases awareness, education and empowerment to facilitate patient-centred decision-making and decrease paternalistic care . In contrast, arguments against DTCA include the high literacy level required, bypassing the patient-provider relationship, overutilization, and increased healthcare costs .
Cancer centres producing DTCA for new radiotherapy technologies was previously questioned with the introduction of Intensity Modulated Radiation Therapy (IMRT) to mainstream radiation oncology practices in the 2000’s . While IMRT implementation was also questioned due to concerns of tumour targeting and risk of secondary malignancies (with larger volumes of normal tissues receiving low dose radiotherapy), the increased costs of IMRT were also a valid concern . While the safety and accuracy of PBT have not been questioned to the same degree, the increased costs of PBT surpass those of IMRT, arising from both high capital costs plus increased reimbursement per fraction . Traditional multi-room proton facilities cost in excess of 100 million USD , though single-room proton machines have now entered the market with a lower capital cost [41, 42]. Recent systematic reviews of the cost-effectiveness of PBT suggest superiority in several disease sites, such as particular pediatric brain tumours, left sided breast cancers at high risk of cardiac toxicity, selected head and neck cancers, and locally advanced lung cancers, acknowledging this finding is limited by the lack of published literature [43, 44].
As cancer care is highly profitable , it should not be surprising that spending on advertising is increasing. In 2014, $173 million was spent on cancer centre advertising in the U.S., roughly triple the amount compared to 2005 . Of the 1500 cancer centres in the U.S., 20 accounted for 86% of advertising spending, of which 9 were NCI-designated . Of these 20 centres, five were included in our study. The advertising practices of cancer centres have previously been brought into question, including appeals to the emotions of a vulnerable patient population, hope for survival, and improved outcomes without supporting factual information, while not mentioning costs or risks associated with treatment [11, 13, 46,47,48]. Our study supports these findings, demonstrating PTC websites frequently offer PBT to non-guideline recommended cancer sites, contain language which evokes hope for better treatment outcomes, and infrequently support all claims made on their website.
It has been argued that randomized clinical trials for PBT are not necessary due to the clear dose distribution advantages over RT [44, 49]. In addition, it has been argued that the capacity constraints of PBT centres precludes the ability to perform randomized clinical trials . While some side effects are likely to be improved with PBT, it is possible that certain side effects, such as skin toxicity, could be expected to be worse with intensity modulated proton therapy . There are over 100 clinical trials underway examining proton radiotherapy, albeit with only eight randomized clinical trials directly comparing proton versus photon radiotherapy . Recently, the first presentation of a randomized study between proton and photon radiotherapy of 147 patients with locally advanced non-small cell lung cancer was published in abstract form, finding no difference in treatment failure or ≥ grade 3 radiation pneumonitis between the two treatment modalities .
In the absence of randomized data, we examined 8 guidelines on proton therapy to identify disease sites indicated for PBT [19,20,21,22,23,24,25,26,27]. These guidelines are from the U.S., Canada, Australia and New Zealand, the U.K., Denmark and the Netherlands. The publication dates range from 2009 to 2017. Guidelines differ on disease site indications, therefore when determining disease sites indicated by guidelines, we used a threshold of at least one guideline indicating a disease site. After review of the international guidelines, there were four disease sites only endorsed by a single guideline (NCCN guidelines). These four sites (prostate cancer, lung cancer, bone cancers and palliative tumours), were considered to be indicated sites for purposes of our study. Prostate cancer was considered an indicated site despite the NCCN guideline also clearly stating that “They believe no clear evidence supports a benefit or decrement to proton therapy over IMRT for either treatment efficacy or long-term toxicity” . Despite retrospective and prospective cohort studies demonstrating favourable side effect profiles for PBT in several disease sites not mentioned in these guidelines (such as pancreas , breast , esophagus  and cervical  cancers), these were not considered indications in our study as they have not been cited in guidelines to date, and are subject to bias.
To our knowledge, this is the first systematic evaluation of DTCA on English PTC websites. However, our data is limited by inconsistencies between how disease sites were listed in international guidelines and websites. For example, many websites did not separate high and low grade gliomas. Several guidelines support the use of PBT for low grade gliomas [19, 21, 24], but no guidelines support the use of PBT in high grade gliomas. Other limitations of our study are excluding ten websites that were not in English. Several international websites that did have an English webpage contained limited information relative to equivalent U.S. websites. As such, our data for these websites may not be completely representative of DTCA towards the primary target audience. Inclusion of a disease site within a guideline is one measure of alignment with evidence based care but has limitations. Guidelines may be limited by the evidence base available or may be influenced by expert opinion depending on the methodology used to generate the guideline. We did not incorporate the availability of pencil beam scanning in our study. Some PTC’s offer both PBT and carbon ion therapy. At times, it was difficult to separate claims for PBT and carbon ion therapy. Finally, the nature of DTCA by an institution does not necessarily reflect the level of discussion that occurs at the provider/patient level. For example, while an indication might be listed on a DTCA website, an informed discussion with the patient may include discussions of alternatives and tailoring of recommendations to that individual’s situation. Such provisos that acknowledge treatments need to be individualized (“check with your doctor if drug x is right for you”) are a mainstay of other forms of DTCA but were not a prominent feature of the websites we examined.