Correspondence
Nephrectomy for Metastatic Renal-Cell Cancer
N Engl J Med 2002; 346:1095-1096April 4, 2002
- Article
To the Editor:
Flanigan et al. (Dec. 6 issue)1 provide evidence that nephrectomy can prolong survival in patients with metastatic renal-cell cancer who are treated with interferon alfa-2b. Although various mechanisms for the survival benefit can be postulated, one possibility not mentioned by the authors or the editorialist2 is that some of the patients in the trial actually had localized, rather than metastatic, disease. Such patients would have had radiologic findings consistent with the presence of metastases, but the results of histologic examination would show that they were not metastatic lesions at all.
It would be valuable to know what radiologic studies were required to determine the eligibility of patients for the study. Was histologic confirmation of at least one metastatic lesion required? Did the response to treatment correlate with long-term survival? Such a correlation would be expected if nephrectomy and interferon had a beneficial effect on the metastases. Finally, did any of the long-term survivors continue to have stable metastatic disease on radiologic examination? If so, were biopsy specimens of these lesions obtained to determine whether they were in fact cancer?
2 ReferencesGraeme Bolger, M.D.
University of Alabama Comprehensive Cancer Center, Birmingham, AL 35294-3300
graeme.bolger@ccc. uab. edu 1
Flanigan RC ,Salmon SE ,Blumenstein BA , et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 2001;345:1655-1659
Full Text | Web of Science | Medline2
Tannock IF . Removing the primary tumor after the cancer has spread. N Engl J Med 2001;345:1699-1700
Full Text | Web of Science | Medline
To the Editor:
Flanigan et al. report the results of a randomized Southwest Oncology Group trial in which nephrectomy followed by interferon alfa-2b was compared with interferon alfa-2b alone for the treatment of metastatic renal-cell cancer. However, they do not provide information regarding the most commonly used prognostic factors for predicting survival in renal-cell cancer (the grade and histologic type of renal-cell carcinoma, the number of metastatic sites, and the levels of serum lactate dehydrogenase, hemoglobin, and calcium).1,2
2 ReferencesM. Sitki Copur, M.D.
Peter Ledakis, M.D.
Max Norvell, Pharm.D.
Saint Francis Cancer Center, Grand Island, NE 68802
mcopur@sfmc-gi.org 1
Motzer RJ ,Mazumdar M ,Bacik J ,Berg W ,Amsterdam A ,Ferrara J . Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17:2530-2540
Web of Science | Medline2
Gelb AB . Renal cell carcinoma: current prognostic factors. Cancer 1997;80:981-986
CrossRef | Web of Science | Medline
To the Editor:
Flanigan et al. report the potential benefit of nephrectomy plus immunotherapy in patients with metastatic renal-cell cancer in terms of survival, but is surgery really worthwhile for such patients? In advanced malignant disease, aggressive treatment such as surgery or interventional endoscopy is usually considered only when it might provide substantial symptomatic relief and thus an improvement in the quality of life. Flanigan et al. do not mention how many patients had symptoms at the time of surgery. Moreover, the difference in median survival between the two groups, though statistically significant, was only three months.
The psychological impact of major surgery and its complications on patients and their families, along with a possibly false increase in the expectation of cure, must be taken into account in the care of patients with a dismal prognosis.
Jorge L. Polo, M.D.
Fundación Jiménez Díaz, Madrid 28040, Spain
polosabau@yahoo.com To the Editor:
Flanigan et al. deserve praise for a well-executed randomized trial that contributes a great deal to our understanding of the management of advanced renal cancer. However, the authors mention only in passing that 23 (11 percent) of the patients “had severe complications due to interferon.” No details about these severe complications are provided, nor is there any mention of the cessation of therapy because of side effects. If clinicians and investigators are to accept this new “standard,” we will need this essential information.
Jonathan D. Schwartz, M.D.
Mount Sinai School of Medicine, New York, NY 10029
jonathan.schwartz@mssm. edu Author/Editor Response
Dr. Flanigan replies:
To the Editor: In response to Dr. Bolger: my colleagues and I used standard radiologic means of identifying and monitoring the metastatic lesions in our patients, including computed tomography, bone scanning, and chest x-ray studies. We did require histologic confirmation of disease before randomization, but the confirmation could be based on the results of biopsy of either the metastatic lesions or the primary tumor. We did find that the tumor response had a pronounced effect on survival. The patients with a response (one with a complete response and four with a partial response) had a mean survival of 2.9 years. Patients with stable disease had a mean survival of 2.1 years: those who underwent nephrectomy and received interferon had a mean survival of 2.9 years, and those who were treated with interferon alone had a mean survival of 1.8 years.
In response to Copur et al.: central pathology review was not required in this trial. For that reason, we did not comment on the pathological grade of the cancers or the effect of grade on survival. To date, we have not reviewed the other determinants of prognosis, including serum lactate dehydrogenase, hemoglobin, and calcium levels, in these patients.
We agree with Polo's view that nephrectomy may not be indicated for everyone with metastatic renal cancer and, in fact, that it should probably be recommended only for those most likely to have increased survival (patients with only lung metastases or with a low volume of metastatic disease). We did not record data on quality of life in our trial and therefore cannot comment on the question about the percentage of patients with symptoms at presentation. We agree that the three-month increase in overall survival in this trial was not a substantial benefit, but we do believe that we demonstrated an increase in survival in patients at good risk.
Finally, we agree with Schwartz that additional information regarding the use of interferon in this trial would be useful. We used a standard dose-reduction regimen: the dose of interferon was halved for any single grade 2 toxic effect and was maintained at that level until the toxic effect had resolved, before administration of the original dose was resumed. Interferon was discontinued if a toxic effect of grade 3 or higher occurred, and treatment was resumed at half the dose if and when the effect resolved. Overall, the schedule of 5 million IU of interferon per square meter of body-surface area three times per week was well tolerated by our patient population.
Robert C. Flanigan, M.D.
Loyola University Stritch School of Medicine, Maywood, IL 60153-5500
rflanig@lumc.edu - Citing Articles (1)
Citing Articles
1
Chris Coppin. (2008) Immunotherapy for renal cell cancer in the era of targeted therapy. Expert Review of Anticancer Therapy 8:6, 907-919
CrossRef
