Correspondence
Unrealistic Expectations in the Diagnosis and Treatment of Ovarian Cancer
N Engl J Med 1993; 328:663-665March 4, 1993
- Article
To the Editor:
Dr. Granai's recent Sounding Board article, “Ovarian Cancer -- Unrealistic Expectations” (July 16 issue),1 succinctly highlights the problem of performing excessive screening tests for diseases for which we have no efficacious treatments. The author uses ovarian cancer as an example. A similar argument can be made for prostatic carcinoma, the most common cancer among American men2. Despite the availability of transrectal ultrasonography, testing for prostate-specific antigen (PSA), and newer agents such as flutamide and leuprolide, the age-adjusted mortality for prostatic cancer has not changed since 19492,3. Moreover, neither PSA testing nor transrectal ultrasonography is recommended as routine screening by the U.S. Preventive Services Task Force4. Nonetheless, I have observed family practitioners and urologists frequently ordering PSA testing as part of the yearly physicals of men. This costly ($70) laboratory test often leads to more costly ultrasonography and biopsy if the PSA level is even slightly elevated.
Until we can truly offer our patients hope for a cure or at least prolonged survival, we should temper our enthusiasm for ordering unnecessary screening tests. The publication from the U.S. Preventive Services Task Force4 is an excellent reference for practicing physicians seeking guidance in health promotion and screening of patients. We must also do a better job of educating our patients who demand to be “tested for cancer.” Perhaps the money saved by avoiding excessive testing could be spent on finding more effective therapies for these common and fatal diseases.
4 ReferencesJeffrey T. Kirchner, D.O.
Lancaster General Hospital, Lancaster, PA 176031
Granai CO . Ovarian cancer -- unrealistic expectations. N Engl J Med 1992;327:197-200
Full Text | Web of Science | Medline2
Silverberg E ,Lubera JA . Cancer statistics, 1989. CA Cancer J Clin 1989;39:3-20
CrossRef | Web of Science | Medline3
Kemp ED . Prostate cancer: finding and managing it. Postgrad Med 1992;92:67-89
Web of Science | Medline4
Preventive Services Task Force. Screening for cervical cancer. In: Guide to clinical preventive services: an assessment of the effectiveness of 169 interventions. Baltimore: Williams & Wilkins, 1989:57-62.
To the Editor:
Dr. Granai incorrectly reports the response rate for taxol in patients with ovarian cancer refractory to standard cisplatin. In the three phase II trials cited,1-3 the response rates actually ranged from 17.6 percent to 31 percent (not 7 percent to 27 percent). Recently, Sarosy et al. observed 19 responses among 46 patients (a 41 percent response rate)4. Some responses have lasted longer than six months and have been associated with marked symptomatic improvements.
On the basis of these studies, the National Cancer Institute freely supplies taxol to cancer centers for patients with refractory disease. Since September 1991, more than 1500 women have been treated; we have complete data on the responses of the first 478. For this compassionate-treatment protocol, eligibility requirements were less restrictive than those of the four phase II trials, but all patients had disease refractory to platinum compounds and had previously received a minimum of three therapies. Nevertheless, 22 percent of the patients have had an objective response. There have been five treatment-related deaths associated with neutropenic fever. Although myelosuppression is noteworthy with the dose of taxol used, serious nausea, vomiting, neurotoxicity, and mucositis are uncommon. Generally, patients prefer taxol to their previous treatments. We know of no better treatment for them, including the alternative therapies described by Dr. Granai, which many patients had already tried.
The principal emphasis of the National Cancer Institute is on sponsoring taxol research designed to optimize the efficacy of the drug; there are more than 60 studies, which will involve several thousand patients. Meanwhile, our obligation is to provide the widest range of legitimate options. Each physician can interpret the emerging data on taxol as he or she wishes and can use these data when offering considered advice to each patient. We also wish to guard against inappropriate optimism, which can lead to cruel disappointment. Defining any particular agent as promising is less important than accurately reporting the facts and allowing the patient to make an informed decision.
4 ReferencesM.A. Friedman, M.D.
B.A. Chabner, M.D.
E.L. Trimble, M.D.
J. Adams, Pharm.D.
S.G. Arbuck, M.D.
National Institutes of Health, Bethesda, MD 208921
McGuire WP ,Rowinsky EK ,Rosenshein NB , et al. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med 1989;111:273-279
Web of Science | Medline2
Thigpen T ,Blessing J ,Ball H ,Hummel S ,Barret R . Phase II trial of taxol as second-line therapy for ovarian carcinoma: a Gynecologic Oncology Group Study. Proc Am Soc Clin Oncol 1990;9:156-156 abstract.3
Einzig AI ,Wiernik PH ,Sasloff J , et al. Phase II study of Taxol (T) in patients (pts) with advanced ovarian cancer. Proc Am Assoc Cancer Res 1990;31:187-187 abstract.4
Sarosy G ,Kohn E ,Link C , et al. Taxol dose intensification (D.I.) in patients with recurrent ovarian cancer. Proc Am Soc Clin Oncol 1992;11:226-226 abstract.
To the Editor:
Dr. Granai's article makes several important points. One issue that deserves further discussion is that cancer care is becoming commercialized or institutionalized both in and outside academic centers, and the self-promotion that often follows may be inherently misleading to the public. Granai cities the example of a hospital that advertised itself “in the state's leading daily newspaper as the regional purveyor of taxol.”
More community- and academic-based practices seem to be institutionalizing their oncology care in a “cancer center” or “cancer institute.” This is sometimes followed by advertising, promotion, and efforts by newly formed public-relations departments to “inform” the public about “special” services that are available in these settings. Unfortunately, this sometimes results in patients' traveling undue distances, past scores of local (and highly qualified) oncologists, for routine or standard care or for experimental care that may not be promising enough to justify the cost, inconvenience, or suffering entailed in such inordinate travel.
As we have discovered in many other situations, if we physicians do not police ourselves, government will intervene and impose measures that may be more drastic and less optimal than recommendations we could design ourselves.
Daniel J. Morris, M.D.
Charles S. Eytel, M.D.
Albert Kerns, M.D.
400 Eighth St., North, Naples, FL 33940To the Editor:
Dr. Granai makes no pointed distinction between the general female population and women who are 35 years old or older and have a family history of ovarian cancer. It was these women, and especially their gynecologists, whom I was trying to reach.
Even more important, my “personal crusade” was to save other Gildas: women with a family history of ovarian cancer who were 35 years old or older, had multiple symptoms, and actually had stage III ovarian cancer that had not been diagnosed (in Gilda's case, for 10 months). In these women, screening with the blood marker CA 125 is 90 percent effective.
Gene Wilder
Stamford, CT 06904Author/Editor Response
Dr. Granai replies:
To the Editor: My article was not offered as a final chapter on taxol or screening for ovarian cancer. Rather, it used both as examples of exaggeration or, worse yet, overt marketing of unproved concepts. Few, I think, would disagree that this practice raises unrealistic expectations, is wrong, and to the extent we physicians are involved, should stop.
Understandably, people in dire circumstances, such as women with progressive ovarian cancer, tend to grasp at anything. To the disdain of all, snake-oil salesmen have long profited from this vulnerability. Now imagine a world where trusted oncologists and institutions engage in unbridled advertising, like supermarkets: “New and improved intraperitoneal taxotere!” As Morris et al. wonder, how will patients choose, even among legitimate treatments?
The emerging data suggest that taxol may be a major anticancer drug1. Everyone is hopeful about this. Still, as I suggested in my article, taxol has repeatedly failed, by common-sense standards, to improve the outcome in patients with refractory ovarian cancer beyond that achieved with readily available, less toxic alternative drugs.
Like Dr. Chabner in his review of taxol,2 I used the standard oncologic terms “partial response” and “complete response,” instead of lumping both into the somewhat inflated summation, “response rate.” When possible, maintaining the separation is enlightening, since a partial response, as a measurement of anticancer treatment, often indicates only a minor improvement according to clinical examination or testing for CA 125. Although scientifically important, lesser responses infrequently translate into real-life improvement for specific patients. Jargon aside, as I suggested and as emphasized by Friedman et al. in their letter, it seems misleading to advertise taxol as promising to women with refractory ovarian cancer or to encourage this belief in their families.
The selfless work of so many against cancer, including thoughtful celebrities such as Gene Wilder, is laudable and generally helpful to society. Sometimes, however, despite the good intentions of individuals or of institutions and the media, expectations have been prematurely or falsely raised, leading to “standards of care” we cannot deliver. I used as an example the current unrealistic expectation that physicians can screen asymptomatic women for early, curable ovarian cancer. Desirable to be sure, such screening is now just not achievable3,4.
Everyone agrees that providing the public with information is essential, but sound-bite marketing tactics common in retail sales should not apply when false expectations are easily generated. Medicine owes society a higher ground, particularly when presenting complex scientific ideas that are critical to decisions made by dying patients. This obligation, not taxol or anything else, is the heart of the matter.
4 ReferencesC.D. Granai, M.D.
Women and Infants' Hospital, Providence, RI 029051
Rowinsky EK ,Donehower RC . Taxol: twenty years later, the story unfolds. J Natl Cancer Inst 1991;83:1778-1781
CrossRef | Web of Science | Medline2
Chabner BA. Taxol. PPO update. Vol. 5. No. 9. Philadelphia: J.B. Lippincott, 1991:1-10.
3
Van Nagell JR Jr ,DePriest PD ,Puls LE , et al. Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography. Cancer 1991;68:458-462
CrossRef | Web of Science | Medline4
Muto MS, Cramer DW, Brown D, et al. Screening for ovarian cancer: preliminary experience of the Familial Ovarian Cancer Center, Brigham and Women's Hospital. Presented at the 12th Annual Meeting of the New England Association of Gynecologic Oncologists, Newport, R.I., June 20, 1992. abstract.
