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The Titanic and the Iceberg: prostate proton therapy and health care economics.

Almost 100 years ago, the Titanic and the iceberg each grew in slow splendor on opposite sides of the wide Atlantic. One, fashioned in the shipyards of Belfast, represented the quintessence of high technology and high finance. The other, patient and brooding in the cold northern waters, was the stern representative of immutable nature. None could guess their ultimate destiny. When the unpredictable yet completely avoidable collision came, it was the hubris of technology that fared worse. At the beginning of this century we, too, are about to witness a collision of two colossi; this time, although quite predictable, it seems unavoidable. The expansive vigor of medical innovation is heading inexorably toward the harsh reality of economic fact. The controversial treatment of prostate cancer epitomizes this clash and represents one sharp point of impact along its very broad front. Sailing forward, powered by the winds of advocacy, of market forces, and of high-stakes investment, is proton therapy: the proud vanguard of modern technology. Elsewhere, waiting patiently in the darkness, are the hard, cold, and unyielding laws of economics. The collision is yet to come, but, with many new proton centers breaking ground, it cannot be far away. Konski et al have made an illuminating and timely contribution to this debate by assessing the potential costs and benefits of proton therapy in contemporary prostate cancer treatment. I say timely because the business model employed by the emerging US proton therapy centers is prostate cancer, and it is on this disease that they will either sink or sail (Note: The author treats prostate cancer with both IMRT and proton beam and the Massachusetts General Hospital and the Francis H. Burr Proton Therapy Center, Boston, MA.). Proton beam therapy (PBT) has been in use for many decades; although its theoretical benefits are not in doubt, there is remarkably little published data strongly supporting its use over other forms of radiation, with the exception of ocular and skull-base tumors and malignancies of children. However, these cancers are rare and the patient demand would be insufficient for new proton therapy centers, or more recently the vendors, to recover their investment. From a commercial perspective, PBT needs to be used for the high-volume treatment of common cancers, and prostate cancer is a perfect fit. PBT has been used in prostate cancer for many decades and there is certainly a growing body of evidence confirming clinical efficacy, but as yet, apart from some comparative planning studies, there is no proof that it is superior to its alternatives. Ten or 15 years ago when the only widely used radiation alternative to proton beam in prostate cancer was twodimensional photon therapy, the superiority of protons could be assumed, given that dose escalation was otherwise simply impossible. Since then, the landscape has changed; three-dimensional therapy and intensity-modulated radiation therapy (IMRT) have narrowed the gap to a degree that truly challenges the underlying premise. Undoubtedly, theoretical advantages still exist. The integral dose to the pelvis with proton beam is lower than that with IMRT, but lateral, the dose through the hips is substantially higher. What then matters more, a low dose to the pelvis or a higher dose to the hips—more rectal or bladder cancers or more hip fractures? If there is a meaningful clinical benefit to PBT in prostate cancer, it can come in one of two ways. Either more radiation can be administered to the prostate than with IMRT, thus increasing the chance for cure, or the same dose of radiation can be administered for a lower risk of adverse effects. Konski et al have examined the first of these propositions. They take the plentiful randomized data supporting dose escalation, speculate that PBT could be used to deliver 91.8 Gy, and calculate, using published dose-response curves, that this will yield a 10% improvement in 5-year freedom from biochemical failure for men with intermediate-risk prostate cancer. The downstream benefits are a reduction in risk of clinical recurrence and consequent use of costly hormonal and chemotherapy. The probability of this benefit being cost effective approaches 50% if the man lives 15 years after therapy and is even higher if he lives longer. The authors calculate that for younger men with this category of disease, the benefit anticipated may just fall within current standards of economic acceptability ($50,000 per qualityadjusted life-year). A number of issues, however, require clarification. First, intermediate-risk prostate cancer represents only 15% to 20% of the total incidence of this disease. Of these men, a large number are diagnosed at age older than 70 years, and with a more limited life expectancy, have relatively little to gain. A significant proportion of the younger patients are already managed more cost-effectively by either surgery or brachytherapy, which in relative terms seem to be a bargain. Unless it is anticipated that many younger men will switch to PBT, these exclusions do not leave too many potential beneficiaries. Of those who may benefit, the cost-benefit calculation is based on one critical assumption: that it is possible to administer 91.8 Gy safely with proton beam. I know of no institution that has even begun to test this. At the Massachusetts General Hospital (Boston, MA) and Loma Linda University Medical Center (Loma Linda, CA), we have completed a pilot protocol delivering JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 25 NUMBER 24 AUGUST 2