Correspondence Re: “Doc, Shouldn’t We Be Getting Some Tests?”
Authors: Bernard Bernhardt, Daniel Hayes, Charles L. Loprinzi, Thomas J. Smith
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.21.3739 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11054451 Correspondence Re: “Doc, Shouldn’t We Be Getting Some Tests?” Bernard BernhardtxBernard BernhardtSearch for articles by this author Daniel HayesxDaniel HayesSearch for articles by this author , Charles L. LoprinzixCharles L. LoprinziSearch for articles by this author , Thomas J. SmithxThomas J. SmithSearch for articles by this author Show More Sound Shore Medical Center New Rochelle, NYGeorgetown University Medical Center Washington, DCMayo Clinic Rochester, MNMedical College of Virginia Richmond, VA https://doi.org/10.1200/JCO.2000.18.21.3739 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01112000In Reply:Dr Bernhardt raises frequently voiced concerns. (1) Are the American Society of Clinical Oncology (ASCO) guidelines regarding monitoring of circulating tumor markers in asymptomatic breast cancer patients who are free of detectable disease incorrect or inconsistent?1-3 (2) Are practice guidelines, in general, too constrictive to be of practical use for individual patients? All three of us are both practicing oncologists and members of one or more guidelines expert panels. Therefore, we share his concerns but believe that both the specific guidelines and the process are valid.First, Bernhardt questions the validity and utility of the specific guidelines for monitoring breast cancer patients after primary and adjuvant therapy. He should be assured that the recommendations of the ASCO expert panels were very thoughtfully (and, on occasion, contentiously) crafted, given the available evidence at the time. In regard to his concern about consistency, improvement in overall survival was not the only criterion for a recommendation. Indeed, the four end points considered were prolongation of overall survival, disease-free survival, quality of life, and/or cost reduction if the first three were equal.4 There is no evidence that initiation of a new systemic therapy in an asymptomatic patient in response to a rising marker (or an asymptomatic, radiographically detected metastasis) results in longer overall survival when compared with initiating the same therapy when symptoms occur.5 Clearly, early treatment is the fundamental tenant of screening for early detection and surgical treatment of new breast cancer and, of course, of application of adjuvant systemic therapy. However, these therapies are administered years before a micrometastasis is destined to appear as a nearly universally incurable recurrence. One could argue that in the classic metastatic setting, the modest survival benefits of recently introduced therapies, such as aromatase inhibitors and trastuzumab, might be enhanced by earlier application. Indeed, both of these therapies are now in or entering prospective randomized clinical trials in the adjuvant setting. However, the average lead time between a rising, circulating tumor marker and detection of a symptomatic metastasis is 3 to 6 months.6 It is difficult to assume that earlier application of treatment because of this short lead time would be likely to result in substantially increased overall survival.Bernhardt should distinguish the potential survival benefits of resection of isolated colon cancer metastases from those of resection of breast cancer metastases. The biology and metastatic patterns of the two seem to differ. In fact, on the basis of a considerable body of evidence, the ASCO tumor marker guidelines panel recommended routine monitoring of circulating carcinoembryonic antigen levels after complete resection in selected colon cancer patients.1,3 Similar data supporting such an approach in breast cancer are lacking.5Does routine tumor marker screening improve quality of life? It is difficult to palliate an asymptomatic patient. However, one could argue that delaying onset of symptoms might result in overall improved global quality of life. Such an approach requires relatively nontoxic therapy to replace whatever therapy (if any) the patient is currently receiving. Perhaps, in postmenopausal patients with estrogen receptor–positive tumors, substitution of aromatase inhibitors for tamoxifen might be successful, but this issue is unstudied. In the absence of a survival benefit, the emotional consequences of identifying impending recurrence might outweigh the benefits of delaying onset of symptoms.One could also argue that a negative test is reassuring to both patient and doctor. However, nearly 50% of all recurrences fail to have a preceding elevation in any circulating tumor marker.6 Furthermore, at any single clinic visit of an asymptomatic patient, the negative predictive value of a nonelevated marker is high, but mostly because it is very unlikely she will have a recurrence in the next 6 months anyway. For example, even for node-positive patients in year 2 or 3, the risk of recurrence is only 6% to 8%.7 In addition, those patients who are reassured by negative test results need to be counterbalanced by the relatively frequent false-positive tests that clearly cause angst.5,6 In the only study that formally examined the issue, quality of life was not better (actually worse, but not statistically significant) in the group who had more intensive monitoring.8Bernhardt questions the consistency between the guidelines regarding tumor markers and those regarding routine office visits. Again, the goals and end points of the recommendation must be considered. We agree that subspecialty office visits are unlikely to improve survival. However, several investigators have addressed the importance of such visits, and at least two prospective randomized trials have been conducted that failed to demonstrate any differences in time to detection of recurrence, medical outcomes, or survival in the group who was observed by subspecialists.9-16 However, in general, results from these and other studies do suggest that patients prefer at least some follow-up with an oncologist. Given the relatively frequent moderate and long-term toxicities of antineoplastic chemo- and endocrine therapies, it seems reasonable to continue some oncologic follow-up. Moreover, it seems likely that oncologists will be better prepared to discuss issues regarding chemo- and surgical prevention, genetic testing, and other concerns. Indeed, it is possible that specialty care might actually decrease costs of follow-up because trained oncologists may be more likely to follow data-driven, evidence-based guidelines than to order a battery of nonindicated tests!Finally, we share Bernhardt’s concerns over whether guidelines should be reconsidered. Do we “lose the trees for the forest?” Are guidelines merely cost savings for the population but not good care for individual patients? The use of evidence-based practice guidelines is a relatively new phenomenon in medicine, and thorough evaluations of their validity and efficacy in improving clinical outcomes are just beginning to appear in the literature. The most comprehensive review of the evidence showed that guidelines improved both process and outcome of medical care in most cases,17 and there is substantial evidence that these improvements extend to oncology.18 Regardless, most oncologists recognize the importance of following strict “protocols,” whether on clinical trials or off. Importantly, the results of a recently reported study suggested that overall survival was longer for Austrian women with newly diagnosed breast cancer who participated in prospective randomized clinical trials compared with those who were treated off-study.19 We recognize that “doctors need to be doctors” and that occasional deviation from clinical guidelines is not only acceptable, it is indicated in some cases. Clearly, the human body and mind are biologic systems, not engineered machines, and 100% adherence to guidelines may well reflect poor consideration for the individual.20 Nonetheless, we are committed to the concept of guideline development and implementation, with the goal of improved patient care but also with the understanding that they are dynamic and require frequent re-evaluation, validation, and modification.1. American Society of Clinical Oncology: Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. J Clin Oncol 14:: 2843,1996-2877, Link, Google Scholar2. American Society of Clinical Oncology: Recommended breast cancer surveillance guidelines. J Clin Oncol 15:: 2149,1997-2156, Link, Google Scholar3. American Society of Clinical Oncology: 1997 update of recommendations for the use of tumor markers in breast and colorectal cancer. J Clin Oncol 16:: 793,1998-795, Link, Google Scholar4. 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Gnant M: Impact of participation in randomized clinical trials on survival of women with early-stage breast cancer: An analysis of 7985 patients. Proc Am Soc Clin Oncol 19:: 74a,,2000 (abstr 287) Google Scholar20. James BC, Hammond ME: The challenge of variation in medical practice. Arch Pathol Lab Med 124:: 1001,2000-1003, Medline, Google Scholar