EISEVIER

l Editorial

RADIOSURGERY, COST-EFFECTIVENESS, GOLD STANDARDS, THE SCIENTIFIC METHOD, CAVALIER COWBOYS, AND THE COST OF HOPE

PAUL W. SPERDUTO, M.D., M.P.P.* AND WALTER A. HALL, M.D.’

*Methodist Hospital Cancer Center, HealthSystem Minnesota, Minneapolis. MN. and ‘Department of Neurosurgery and Radiation Oncology, University of Minnesota Hospital and Clinic, Minneapolis. MN

“The greater the ignorance, the greater the dogmatism,’ ’ (5). These words of Sir William Osler written over a cen- tury ago apply to the current debate regarding the man- agement of patients with a solitary brain metastasis, as well as other oncologic controversies of our day. The re- cent article by Auchter et al. (1) and the accompanying editorial by Flickinger and Kondziolka (3) provide elo- quent support for changing the standard treatment for pa- tients with a solitary brain metastasis from surgery and whole brain radiation therapy (WBRT) to WBRT plus ste- reotactic radiosurgery (SRS). This issue is an excellent example of an evolving phenomenon that is happening in many areas of modern American health care. The complex interrelationships of cost-effectiveness, the gold standard du jour, the scientific method, and the cost of hope are often in uneasy balance. direct conflict, and/or fraught with perverse incentives.

There are several troubling aspects of this phenomenon that warrant our awareness. In the case of the estimated 90,000 Americans who will develop solitary brain metas- tases this year, cost-effectiveness studies and retrospective series favor WBRT plus SRS. This approach is further promulgated because it is compatible with the patient and family’s need to do more for such a deadly disease. The cost of hope can be enormous in oncology as patients search for their miracle. The concerns are many. If we espouse this new gold standard, are we not proving Osler’s aphorism, exchanging one dogma for another without pro- spective randomized data? Is this not blatant disregard for the scientific method brought about by a new technology looking for an indication and potentially perverse financial incentives? (Doctors desire to use the new technology, administrators’ and insurance carriers’ desire to cut costs, and patients’ willingness to pay any cost for hope.) An- other major concern is the wanton application of the new technology when clinicians inappropriately extrapolate the existing data to other clinical situations. For example,

it is entirely unclear if patients with multiple brain metas- tases benefit and highly dubious that anyone with pro- gressive systemic disease would benefit in any significant way. While learned colleagues argue that it is unethical to wait for prospective randomized data to confirm our every innovation, especially one with sound retrospective sup- port, this advance in the clinical judgment of a few must be balanced with the fear that the cavalier cowboys of our discipline will apply the new technology with clinical mis- judgment. Learned colleagues argue further that misap- plications will always occur and that we are not respon- sible for every cavalier cowboy. I vehemently disagree. If we do not support prospective randomized trials, we wiil never define which subsets of patients rruly benefit from the new technology.

The Radiation Therapy Oncology Group (RTOG) is aware of these problems. RTOG 9508 randamizes patients with 1 to 3 metastases to WBRT vs. WBRT plus SRS. It is stratified by the number of metastases (one vs. two or three) and by the extent of extracranial metastases (present vs. absent). As a principal investigator (PWS) for this pro- tocol, I have received numerous phone calls from radiation oncologists around the country stating they and/or their IRB are reticent to participate in the trial because they feel it is unethical to deprive a patient of SRS based on the weight of the retrospective data referenced above. And yet, many of these patients had multiple metastases or un- controlled (or even unevaluated) systemic disease. If this is the interpretation of the articles by Auchter et al. and Flickinger and Kondziolka, a disservice has been uninten- tionally perpetrated on our patients. I strongly encourage participation in RTOG 9508. the results of which are clearly still needed to better define the role of SRS in patients with brain metastases.

In a related action, the RTOG has recently endorsed a companion trial for iis radiosurgery trials that surveys the insurance industry preapproval decision for SRS. A sim-

Reprint requests to: Paul W. Sperduto, M.D., M.P.P., Meth- sota, Minneapolis, MN S.5440. odist Hospital Cancer Center. Box 650. HealthSystem Minne- Accepted for publication 2 July 1946

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ilar survey in women with breast cancer requesting cov- erage for autologous bone marrow transplantation found the decision process was arbitrary and capricious (6). The results of this survey should provide powerful evidence regarding whether the insurance preapproval decision is based on the best available knowledge or, on the other hand, is arbitrary and capricious. Unfortunately, in the era of managed care, the insurance carriers play an ever grow- ing role in clinical decision making. They must, therefore, be held responsible for their decisions. This simple survey study will provide a measure of carrier accountability.

An incremental cost-effectiveness analysis of these al- ternative treatments was performed, from the society per- spective, using average Medicare reimbursement at Meth- odist Hospital, HealthSystem Minnesota, Minneapolis, MN, as an indicator of cost and the percent local control at 1 year, based on a review of the literature, as an indi- cator of effectiveness. The methodology of incremental cost-effectiveness analyses provides a quantitative com- parison of the change in outcome for each successively more expensive treatment alternative. The costs (average Medicare reimbursement) for (a) no treatment, (b) WBRT alone, (c) WBRT plus SRS, and (d) surgery plus WBRT were $0, $1702, $6452, and $17,061, respectively. The effectiveness (percent local control at 1 year) for the same options were O%, 52%, 85%, and 80%, respectively. The average cost/effectiveness ($/% local control) for the same options were $0, $33, $76, and $213, respectively. The marginal (incremental) cost/effectiveness ($/additional % local control) for the same options were not applicable (no cheaper treatment for comparison), $33, $144, and not applicable (no benefit for this more expensive option).

Why has this issue captured what may seem to be a disproportionate amount of attention by our journals and national meetings, not to mention our vendors of technol- ogy? The answer is simply that the management of pa- tients with a single brain metastasis is an issue of increas- ing clinical and economic importance. A recent cost-effectiveness analysis (8) evaluated four options: (a) no treatment; (b) whole brain radiation therapy (WBRT) alone; (c) WBRT plus stereotactic radiosurgery (SRS), and (d) surgery and WBRT. This analysis concluded WBRT plus SRS is more effective (improved local con- trol) than WBRT alone and that WBRT plus SRS is more cost-effective than surgery plus WBRT. For these reasons, in many institutions, WBRT plus SRS is already the stan- dard of care for patients with solitary brain metastases who have stable systemic disease, adequate performance status (Karnofsky Performance Status > 60), and do not require relief from mass effect within the brain. Rutigliano et al. (7) performed a similar analysis with similar conclusions.

In an effort to define the magnitude of the economic impact of such conchisions, we extrapolated our data na- tionwide. There were approximately 1,252,OOO new cases

of invasive cancer diagnosed in the United States in 1995 (9). Symptomatic brain metastases will develop in 13.5% or 169,020 of these patients (10). Half (or 84,510) of these patients (10) will have solitary brain metastases by CT scan (2) and somewhat fewer, an estimated 60,000, will have solitary brain metastases by MRI scan. Based on the experience at the University of Minnesota between 1973 and 1993 (4), it can be estimated that approximately 40% (34,649 by CT, 24,600 by MRI) of these patients will have controlled systemic disease and adequate performance status to justify surgical resection. It is estimated that one- third of these patients will require relief from mass effect, an absolute indication for surgery. The other two-thirds (or 23,215 by CT, 16,482 by MRI) of these patients rep- resent the group that is currently treated with surgical resection and WBRT who could be treated with WBRT plus SRS.

The marginal cost of surgery plus WBRT compared to WBRT plus SRS ranges from $10,609 (average Medicare reimbursement) to $15,236 (average private insurance re- imbursement) (8). To calculate the potential annual sav- ings to society based on the Medicare data, one multiples 16,482 patients/year X $10,609 savings/patient for a total savings of an astounding $175 million/year in the United States alone. This represents the most conservative esti- mate, based on Medicare data, not private insurance reimbursement.

In summary, standard therapy for patients with a soli- tary brain metastasis should be as follows: patients with uncontrolled systemic disease or poor performance status (KPS < 60) should receive WBRT and steroids; patients with controlled systemic disease and adequate perfor- mance status should receive WBRT plus SRS; and pa- tients who require relief from mass effect, have stable sys- temic disease, and adequate performance status should undergo surgical resection and WBRT. Participation in RTOG or other clinical trials should be encouraged. Until such trials are complete, the cost-effective management of patients with solitary brain metastases could save society $175 million each year. In an era of limited resources and managed care, the medical profession, administrators, and insurance carriers must become more responsible in its allocation of scarce resources. Even though such a state- ment reeks of managed care bureau-babble, evoking a re- action in most physicians somewhere between anaphy- laxis and status epilepticus, it is true. More importantly, all of us must be aware of the complex interrelationships, uneasy balance, conflict, and perverse incentives cloaked by cavalier cowboys as cost-effectiveness and the pursuit of progress, when in fact it is a wanton disregard for the scientific method, preying on patients willingness to pay any price for hope. Without such awareness, we have all participated in an elaborate proof of Osler’s aphorism. Without such awareness, dogma reigns and ignorance stands tall.

Radiosurgery, cost-effectiveness, gold standards 0 P. W. SPEKDIVO I\Nll W. A. H j*.i 5 I .;

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