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 ␣-2b vs interferon ␣-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 ϭ 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.

Local treatments for metastases of renal cell carcinoma: a systematic review

“…3 For synchronous metastatic renal cell carcinoma, cyto reductive nephrectomy in combination with treatment with interferon alfa resulted in a signifi cant improve ment in median overall survival compared with treatment with interferon alfa alone. 4 However, in the era of targeted treatment the role of cytoreductive nephrectomy is not well defi ned. With present targeted drugs, the proportion of patients achieving an objective response has been between 20-40%, but complete responses were reported in only 1-3% of patients.…”

Cytoreductive Surgery in the Management of Renal Tumours: Rationale, Current Evidence and Future Perspectives

“…There was a twofold increase in the overall survival of 19.8 months for the CRN group versus 9.4 months for the TT only group (HR 0.44; p < 0.01). This survival benefit was persistent on multivariate analysis, but a group of patients Combined analysis [9] No. of pts 161 163 Median survival (months) 13.6 7.8 1-year survival (months) 51.9 37.1 pts patients with a poor risk or with a KPS score of less than 80% had only marginal survival benefit with CRN [21].…”

“…One-year survival was 51.9 versus 37.1 months, respectively, with a hazard ratio (95% CI) of 0.69 (0.55-0.87) [9]. Table 1 illustrates the details of the EORTC study, SWOG study and their combined analysis.…”

“…Interferon alpha 2-b was considered safer than interleukin-2; the latter had high toxicity profile, had to be administered in the hospital setting, and was costly. Two major randomised controlled trials (European Organisation for Research and Treatment of Cancer (EORTC) 30947 and Southwest Oncology Group (SWOG) 8949) and their combined analysis showed significant survival benefit when patients with metastatic RCC (mRCC) were treated with cytoreductive nephrectomy and interferon alpha 2-b versus interferon alpha 2-b alone [7][8][9].…”

Prise en charge du cancer du rein de stade avancé : Mise à jour 2013 des lignes directrices consensuelles du Forum canadien sur le cancer du rein

“…Les décisions doivent être prises par extrapolation à partir (1) des données sur l'interféron; (2) des données rétrospectives d'études nord-américaines montrant une amélioration des résultats chez les patients ayant subi une néphrectomie cytoréductrice avant le recours à un traitement ciblé; (3) du fait que la plupart des patients (> 90 %) inscrits aux essais cliniques de phase III portant sur les ITK du VEGFr avaient déjà subi une néphrectomie cytoréductrice; et (4) en fonction du jugement clinique 9,20,32,[39][40][41] . Des études prospectives sur les bienfaits de la néphrectomie cytoréduc-trice doivent être menés, et plusieurs essais sont en cours.…”