Pounds of prevention for ounces of cure: surgery as a preventive strategy
Authors: David E Wennberg, John D Birkmeyer, FL Lucas
Journal: The Lancet (1999)

By reducing procedure-related risks and recovery times, new surgical techniques have profoundly changed clinical decision-making for many common diseases. A radical change is the use of surgery as a preventive strategy in symptom-free patients—for instance, endovascular repair of small (<5 cm) abdominal aortic aneurysms. The increasing application of "preventive surgery" has important implications for the delivery of health care. For the patient, availability of new surgical techniques is fundamentally changing the trade-offs between up-front risk and future benefits. For the population, earlier intervention is intricately linked to earlier diagnosis, with substantial implications for public health and society's ability to pay for early diagnosis and treatment. Whether preventive surgery will be "good" for patients depends on how it affects the fragile balance between the benefits and risks of intervention in different clinical conditions. The benefits likely to be achieved by earlier intervention are difficult to predict; however, they may be smaller than the benefits associated with surgery later in the course of disease. New techniques are constantly being developed and existing techniques constantly being refined; both are diffusing into the community faster than the rate at which their risks can be evaluated. Moreover, studies reporting new interventions usually originate from highly selected referral centres and commonly do not reflect risks likely to be observed in actual practice. For example, the benefits of carotid endarterectomy—the quintessential preventive procedure—diminish as it is applied earlier in the course of carotid disease. In the North American Symptomatic Carotid Surgery Trial (NASCET), carotid endarterectomy reduced the absolute risk of ipsilateral stroke or death by 5% per year1North American Symptomatic Carotid Surgery Trial Steering Committee Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis.N Engl J Med. 1991; 325: 445-453Crossref PubMed Scopus (7609) Google Scholar This large benefit reflected the high rate of stroke among those treated medically. The Asymptomatic Carotid Artery Study (ACAS) also suggested that carotid endarterectomy is effective in symptom-free patients. However, in ACAS the absolute risk reduction was only 1 % per year.2Executive Committee for the Asymptomatic Carotid Atherosclerosis Study Endarterectomy for asymptomatic carotid artery stenosis.JAMA. 1995; 273: 1421-1428Crossref PubMed Scopus (5004) Google Scholar The positive results in ACAS were highly dependent on the low pen-operative mortality rate achieved in the highly selected hospitals participating in the trial. What are the risks in the "real world"? For carotid endarterectomy there is evidence that performance in usual practice does not approximate that achieved in the trials. In a study of 113 000 Medicare patients undergoing carotid endarterectomy in 1992-93, the peri-operative mortality (1·8%) was higher than that reported in the trials (0·1% in ACAS and 0·6% in NASCET).3Wennberg DE Lucas FL Birkmeyer JD Bredenberg CE Fisher ES Variation in carotid endarterectomy mortality in the Medicare population: trial hospitals, volume, and patient characteristics.JAMA. 1998; 279: 1278-1281Crossref PubMed Scopus (447) Google Scholar Even among those hospitals that participated in ACAS and NASCET, mortality in their unselected Medicare patients was 1·4%. For patients who underwent carotid endarterectomy in hospitals that did not participate in the trials, mortality was higher and ranged from 1·7% in high-volume (for carotid endarterectomy) hospitals to 2·5% in low-volume hospitals. The dissimilarity between what was reported in the trials and what is found in usual practice is a combination of the careful selection of centres and of patients in the trial. Only 3·2% of hospitals doing carotid endarterectomies in the USA participated in the trials; in ACAS for every patient randomised, 25 had been screened. Figure 1 depicts the fragile balance between the benefits and risks of intervention early in the course of disease, and how sensitive the balance is to the risk of the procedure. In hospitals with high pen-operative mortality, benefits may be realised only with very ill patients. What reduces risk for individual patients may not reduce risk for the population. Although new techniques generally reduce the procedure-related risk, they also tend to expand the list of surgical indications for the technique. More patients will undergo procedures and be exposed to procedure-related risks. Consider the case of laparoscopic cholecystectomy, an alternative to open procedures for patients with gallstone disease. After its introduction in the late 1980s and its rapid diffusion, laparoscopic cholecystectomy largely replaced open procedures, with a decrease in the case fatality rate.4Steiner CA Bass EB Talamini MA Pitt HA Steinberg EP Surgical rates and operative mortality for open and laparoscopic cholecystectomy in Maryland.N Engl J Med. 1994; 300: 403-408Crossref Scopus (288) Google Scholar However, the enthusiasm for this procedure also lowered the threshold for cholecystectomies, which resulted in a greater than 20% increase in the population-based rates of cholecystectomies over a 5-year period.5Escarce JJ Chen W Schwartz S Falling cholecystectomy thresholds since the introduction of laparoscopic cholecystectomy.JAMA. 1995; 273: 1581-1585Crossref PubMed Scopus (126) Google Scholar With more persons now at risk, the total number of cholecystectomy deaths in the population either stayed the same or, in some regions, increased by over 10%; 4Steiner CA Bass EB Talamini MA Pitt HA Steinberg EP Surgical rates and operative mortality for open and laparoscopic cholecystectomy in Maryland.N Engl J Med. 1994; 300: 403-408Crossref Scopus (288) Google Scholar, 6Nenner RP Imperato PJ Rosenberg C Ronberg E Increased cholecystectomy rates among Medicare patients after the introduction of laparoscopic cholecystectomy.J Community Health. 1994; 19: 409-415Crossref PubMed Scopus (31) Google Scholar Advances in surgical treatment share the medical stage with a second technological revolution: diagnostic testing. Not only is disease being treated earlier than in the past, it is being detected earlier, and more of it is being found. Earlier detection has implications for the understanding of the natural history of disease and thus the benefits likely to be achieved by preventive surgery. Consider diagnostic advances in breast cancer. Improvements in mammography created a new "epidemic": between 1983 and 1992, the incidence of ductal carcinoma in situ (DCIS) increased by over 200%.7Ernster VL Barclay J Kerlikowske K Grady D Henderson IC Incidence of and treatment for ductal darcinoma in situ of the breast.JAMA. 1996; 276: 913-918Crossref Google Scholar Despite the recent adroitness at discovering DCIS, knowledge about its natural history is limited. What denotes risk for DCIS? Is it size, multifocality, or patterns? The uncertainty about the natural history of DCIS is reflected in the striking variability in how physicians manage this "disease". Depending upon where women live, the likelihood of having a mastectomy for DCIS can more than double.7Ernster VL Barclay J Kerlikowske K Grady D Henderson IC Incidence of and treatment for ductal darcinoma in situ of the breast.JAMA. 1996; 276: 913-918Crossref Google Scholar With genetic markers such as BRCA1 the inherent uncertainty about the natural history of early diagnosis is amplified several fold. BRCAI is not a test for the diagnosis of a disease, but rather a means of diagnosing a predisposition for disease. But what is the risk of disease in those who test positive? It is now known that most women with breast cancer do not have a BRCA1 mutation,8Newman B Mu H Butler LM Millikan RC Moorman PG King MC Frequency of breast cancer attributable to BRCA1 in a population-based series of American women.JAMA. 1998; 279: 915-921Crossref PubMed Scopus (318) Google Scholar Still unknown is what proportion of women in the general population who test positive have breast cancer. What is certain, however, is that as information about BRCA1 is disseminated, more women will ask to be screened for the gene. How many of those who test positive should undergo prophylactic mastectomy? As diagnostic testing improves and becomes more acceptable to patients, more disease will be found. As surgical technology improves, clinicians will intervene earlier in the course of disease. The confluence of technological advances in diagnosis and intervention has set the stage for an explosive growth in the use of surgery as a preventive strategy.9Verriilli D Welch HG The impact of diagnostic testing on therapeutic interventions.JAMA. 1996; 275: 1189-1191Crossref PubMed Google Scholar In ACAS, carotid angiography was a major source of morbidity, which led some clinicians to recommend that duplex sonography replace angiography as the gold standard for case-finding and pre-operative assessment. Duplex ultrasonography is safe and painless, So more patients will be willing to undergo testing if this method is used. How much disease is there to discover? In the Framingham Study, the prevalence of significant carotid stenosis >50% among people aged over 65 years was 9%.10Fine-Edelstein JS Wolf PA O'Leary DH et al.Precursors of extracranial carotid atherosclerosis in the Framingham study.Neurology. 1994; 44: 1046-1050Crossref PubMed Google Scholar Extrapolation of this finding to the population of the USA means that there is a reservoir of 33 00 000 candidates for carotid endarterectomy. Will doctors look for cases? There is anecdotal evidence that in the USA there are "shopping-mall" clinics to screen for carotid artery disease. Will clinicians treat? Apparently yes. An analysis of the use of duplex ultrasonography and carotid endarterectomy across 306 geographically discrete populations in the USA showed that age, sex, and race adjusted rates of carotid duplex ultrasonography varied from 20 per 1000 to 110 per 1000 Medicare enrollees.11Wennberg JE Cooper MM The quality of medical care in the United States: a report on the Medicare program (The Dartmouth Atlas of Health Care 1999). American Hospital Publishing, Inc, Chicago1999Google Scholar Similar variability was found in the adjusted rates of carotid endarterectomy: from 1·8/1000 to 6·4/1000 Medicare enrollees. What was more striking than the variability in prevalence of diagnostic testing and treatment was the strong, positive linear relation between rates of duplex ultrasonography and of carotid endarterectomy (figure 2). The cost implications of treating the population in an area with a high prevalence of diagnostic investigation and intervention are obvious. The contrast between benefits in symptomatic and symptom-free disease, the difference between efficacy outcomes (outcomes in ideal settings) and effectiveness (outcomes in usual practice), the uncertainty about the natural history of disease diagnosed early, and the bottomless reservoir of surgically treatable disease lead to the following observations. •The less severe the disease, the better the performance must be to tip the risk ratio towards intervention. In the symptom-free patient, risk may need to be zero. Achievement of zero risk may be impossible in the real world.•As surgical techniques improve, they will rapidly diffuse. Diffusion may lead to lowering of treatment thresholds. Lowering of treatment thresholds may increase total treatment morbidity in the population.•To assess benefit and risk accurately, information is needed of the benefits associated with alternative treatments. Benefits become more difficult to define as improvements in diagnostic technology fundamentally challenge notions of what disease is.•As diagnostic testing improves, more people will be tested. As more people are tested, more will be treated. The spiral of earlier diagnosis and earlier treatment will increase costs, but may not lead to an improvement in the health of the population.•The more one looks, the more one find; the more one finds, the more one does. Diagnosing and treating millions of people for diseases with unknown natural history will lead to spending billions of £s for prevention. The question is will it lead to ounces of cure? Supported in part by a grant from the Robert Wood Johnson Foundation.