Intensive diagnostic follow-up did not improve survival in breast cancer
ACP J Club. 1994 Nov-Dec;121:77. doi:10.7326/ACPJC-1994-121-3-077
Rosselli Del Turco M, Palli D, Cariddi A, et al. Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. JAMA. 1994 May 25;271:1593-7.
To study whether the addition of scheduled chest roentgenography and bone scans during follow-up increases survival in women with breast cancer.
Randomized controlled trial with minimum follow-up of 5 years.
12 breast clinics in Italy.
1243 consecutive women who had breast cancer surgery in the previous 6 months. Inclusion criteria were unilateral, histologically confirmed invasive carcinoma of the breast with no evidence of distant metastases, age ≤ 70 years, and no cancer diagnosed at another site.
All women had annual mammography and were seen every 3 months for 2 years and then every 6 months for 3 years. National protocols were used for all postoperative treatments. Randomization was stratified by center. 621 women were allocated to receive usual care and diagnostic tests were ordered as clinically indicated. 622 women were allocated to usual care plus scheduled chest roentgenography and bone scan every 6 months. Follow-up for mortality was > 99%.
Main outcome measures
Survival and relapse-free survival.
The groups did not differ in 5-year survival (116 deaths [18.6%] in the intensive follow-up group vs 121 deaths [19.5%] deaths in the usual care group) (Table). 393 recurrences were observed (104 local and 289 distant). Compared with women in the usual care group, women in the intensive follow-up group had a lower recurrence-free survival at 5 years (64.8% vs 72.0%, P < 0.05) (Table). Women in the intensive follow-up group had earlier diagnosis of distant recurrences (P = 0.01). This difference was reduced when first metastasis or death, whichever came first, were analyzed together (P = 0.07).
Scheduled chest roentgenography and bone scan allowed earlier detection of metastases in women who have had surgery for breast cancer. The earlier detection did not improve 5-year survival.
Source of funding: National Research Council of Italy.
For article reprint: Dr. M. Rosselli Del Turco, Azienda Ospealiera Careggi, Presidio per la Prevenzione Oncologica, Viale A. Volta, n.171-50131, Florence, Italy. FAX 39-55-5001623.
Table. Intensive follow-up vs usual care for breast cancer*
|Outcomes at a minimum follow-up of 5 y||Intensive follow-up||Usual care||RRR (95% CI)||NNT|
|Death||19%||19%||4% (-20 to 23)||Not significant|
|RBR (CI)||NNH (CI)|
|Recurrence-free survival||65%||72%||10% (3 to 17)||14 (9 to 50)|
*RBR = relative benefit reduction. Other abbreviations defined in Glossary; RRR, RBR, NNT, NNH, and CI calculated from data in article.
These 2 studies, which examined the benefits of routine diagnostic testing in asymptomatic women who are being followed for nonmetastatic breast cancer, are important. Both were randomized trials in women with nonmetastatic breast cancer: 1 group had routine diagnostic testing (annual chest roentgenography, bone scan, liver ultrasound, alkaline phosphatase and gamma-glutamyl transpeptidase measurements in 1 study and chest roentgenography and bone scan every 6 months in the other study), whereas the comparison group was followed by physician assessment and mammography with diagnostic tests done only when there was clinical suspicion of metastases.
The results of these well-designed clinical trials are remarkably similar. First, and most important, neither study showed a survival benefit in women who had routine diagnostic testing. This indicates that even though routine testing may detect asymptomatic metastases early, this does not translate into a survival advantage if patients are followed clinically and widely accepted treatment protocols are used when metastatic disease is identified. That these observations were made in randomized clinical trials overcomes the effects of lead-time or length-time biases that may have been present in previous nonrandomized studies, thereby strengthening the clinical relevance and validity of the results. These results should allay concerns that physicians are jeopardizing their patients' survival if they do not do routine diagnostic testing during follow-up of primary breast cancer.
The GIVIO investigators extended these observations to show that routine diagnostic testing did not improve health-related quality of life, at least when quality of life was measured annually. It is possible that the investigators missed short-term differences in quality of life caused by the anxiety associated with routine testing (e.g., waiting for test results, reacting to positive test results) or an unsatisfied desire for testing as a means of reassurance that a recurrence has not occurred. These possibilities should be explored in future investigations. This is particularly important because the GIVIO investigators identified a clear wish on the part of women in both of their study groups to have routine diagnostic tests done even if they were asymptomatic.
Although 1 of the studies showed that recurrences were diagnosed earlier in women who had routine diagnostic testing, neither study showed a survival benefit, the most clinically relevant outcome in this group of patients. Early diagnosis of recurrence that cannot be translated into an increase in survival simply lengthens the time during which a woman must live with the knowledge that she has an incurable disease, a situation that is not desirable. Given these results, routine diagnostic testing in patients with breast cancer should not be done during follow-up of women who are asymptomatic, although a role for these tests in certain research situations may exist. All women in these studies had routine physician assessment (history and physical examination) and annual mammography. Because these procedures may detect locoregional recurrences before systemic spread, it is quite possible they may help improve survival. History and physical examination should remain the cornerstone of the follow-up for women with nonrecurrent breast cancer until further information becomes available.
Pamela J. Goodwin, MD, MSc
Mount Sinai HospitalToronto, Ontario, Canada