Flanigan Robert C, Mickisch G, Sylvester Richard, Tangen Cathy, Van Poppel H, Crawford E David
Southwest Oncology Group and European Organization for the Research and Treatment of Cancer Genitourinary Group, Loyola University Medical Center, Maywood, Illinois, USA.
J Urol. 2004 Mar;171(3):1071-6. doi: 10.1097/01.ju.0000110610.61545.ae.
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.
A total of 331 patients were randomized to 2 identical protocols comparing cytoreductive nephrectomy plus interferon alpha-2b vs interferon alpha-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.
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.
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.
转移性肾癌预后较差。针对这一问题的免疫治疗新进展重新引发了对减瘤性肾切除术的兴趣。我们报告了两项采用相同研究方案的前瞻性随机试验的联合分析结果。
共有331例患者被随机分为两个相同方案组，比较减瘤性肾切除术联合α-2b干扰素与单纯α-2b干扰素治疗转移性肾癌患者的疗效，这些患者存在原发肿瘤且认为可切除。每项试验的主要终点是总生存期，次要终点是缓解率。患者在随机分组前根据体能状态（0或1）、转移部位（仅肺转移与其他部位转移）和疾病可测量性进行分层。所有结果均根据意向性治疗标准进行分析。假设单纯干扰素治疗的中位生存期为1年，西南肿瘤协作组试验旨在检测中位生存期提高50%和缓解率提高15%，检验效能为0.85。欧洲癌症研究与治疗组织在该研究中额外纳入了80例患者。
这两项试验的联合分析显示，肾切除术联合干扰素组的中位生存期为13.6个月，单纯干扰素组为7.8个月。这种差异表明死亡风险降低了31%（p = 0.002）。根据随机分组前的分层因素，未发现治疗效果大小存在差异。
对于接受干扰素免疫治疗的转移性肾癌患者，减瘤性肾切除术似乎能显著提高总生存期，且与患者体能状态、转移部位及疾病可测量性无关。尽管在统计学上具有高度显著性，但整个组的总生存期优势仅为5.8个月。这些数据强调需要确定在减瘤性肾切除术的背景下，使用更积极的免疫治疗或其他新型药物是否能进一步提高这种生存优势。
