Cytoreductive Nephrectomy in Patients With Metastatic Renal Cancer: A Combined Analysis
Abstract
Purpose:
Metastatic renal cancer is associated with a poor prognosis. Recent advances in immunotherapy for this problem have rekindled interest in cytoreductive nephrectomy. We report a combined analysis of 2 prospective randomized trials that used an identical study protocol.
Materials and Methods:
A total of 331 patients were randomized to 2 identical protocols comparing cytoreductive nephrectomy plus interferon α-2b vs interferon α-2b alone in patients with metastatic renal cancer, in whom the primary tumor was present and believed to be resectable. The primary end point for each trial was overall survival with a secondary end point of the response rate. Patients were stratified at pre-randomization by performance status (0 or 1), site of metastases (lung only vs other) and disease measurability. All results were analyzed by intent to treat criteria. Assuming a median survival of 1 year for interferon only, the Southwest Oncology Group trial was designed to detect a 50% improvement in median survival duration and a 15% improvement in response rate with a power of 0.85. The European Organization for the Research and Treatment of Cancer accrued an additional 80 patients in that study.
Results:
The combined analysis of these 2 trials yielded a median survival of 13.6 months for nephrectomy plus interferon vs 7.8 months for interferon alone. This difference represents a 31% decrease in the risk of death (p = 0.002). There was no evidence of a difference in the size of the treatment effect according to pre-randomization stratification factors.
Conclusions:
Cytoreductive nephrectomy appears to improve significantly overall survival in patients with metastatic renal cancer treated with interferon immunotherapy independent of patient performance status, the site of metastases and the presence of measurable disease. Although it is highly statistically significant, the overall survival advantage is only 5.8 months for the entire group. These data emphasize the need to determine if this survival advantage can be further improved using more aggressive immunotherapy or other novel agents in the setting of cytoreductive nephrectomy.
References
- 1 : Nephrectomy followed by interferon-alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med2001; 345: 1655. Google Scholar
- 2 : Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon-alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet2001; 358: 966. Google Scholar
- 3 : Systemic therapy for renal cell carcinoma. J Urol2000; 163: 408. Link, Google Scholar
- 4 : Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor. J Urol1997; 158: 740. Link, Google Scholar
- 5 : Immunotherapy with interleukin-2 and alpha interferon in patients with metastatic renal cell cancer in situ primary cancers: a pilot study. J Urol1992; 147: 24. Abstract, Google Scholar
- 6 : Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells. J Urol1990; 144: 614. Link, Google Scholar
- 7 : The impact of adjuvant nephrectomy on the multimodality treatment of metastatic renal cell carcinoma. J Urol1994; 152: 1399. Abstract, Google Scholar
- 8 : Prognostic factors for survival in patients with metastatic renal cancer treated with biological response modifiers. J Urol1995; 154: 35. Link, Google Scholar
- 9 : Reassessment of the selection criteria for cytoreductive nephrectomy in patients with metastatic renal cell carcinoma. J Urol2000; 163: 179. abstract 793. Google Scholar
- 10 : Clinical variables that predict survival following cytoreductive nephrectomy for metastatic renal cell carcinoma. J Urol2001; 165: 184. abstract 763. Google Scholar
- 11 : Cytoreductive surgery prior to interleukin-2-based therapy in patients with metastatic renal cell carcinoma. Urology1993; 42: 250. Google Scholar
- 12 : Nephrectomy before interleukin-2 therapy for patients with metastatic renal cell carcinoma. J Urol1997; 158: 1691. Link, Google Scholar
- 13 : Cytoreductive surgery before high dose interleukin-2 based therapy in patients with metastatic renal cell carcinoma. J Urol1997; 158: 1675. Link, Google Scholar
- 14 : Laparoscopic cytoreductive nephrectomy as preparation for administration of systemic interleukin-2 in the treatment of metastatic renal cell carcinoma: a pilot study. Urology1999; 53: 496. Google Scholar
- 15 : Laparoscopic cytoreductive radical nephrectomy for metastatic renal cell carcinoma: a feasibility study. J Urol2001; 165: 185. abstract 764. Google Scholar
- 16 : Survival advantage of interleukin-2 over interferon immunotherapy when combined with cytoreductive nephrectomy based on SWOG 8949-matched populations. J Urol2002; 167: 166. abstract 666. Google Scholar
- 17 : Presentation of renal tumor antigens by human dendritic cells activates tumor-infiltrating lymphocytes against autologous tumor: implications for live kidney cancer vaccines. Clin Cancer Res1999; 5: 445. Google Scholar
From the Southwest Oncology Group and European Organization for the Research and Treatment of Cancer Genitourinary Group, Loyola University Medical Center (RCF), Maywood, Illinois, Centrum Fuer Operative Urologie (GM), Bremen, Germany, European Organization for the Research and Treatment of Cancer Data Center (RS), Brussels and UZ Gasthuisberg (HVP), Leuven, Belgium, Southwest Oncology Group Statistical Center (CT), Seattle, Washington, and University of Colorado Medical Center (EDC), Denver, Colorado
