Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Urol Oncol. 2022 Jan;40(1):13.e19-13.e27. doi: 10.1016/j.urolonc.2021.09.014. Epub 2021 Oct 27.
With the emergence of several effective combination therapies, information on their effects at the primary site will be crucial for planning future cytoreductive nephrectomy (CN). The present study focused exclusively on changes in primary tumor sizes following treatment with nivolumab plus ipilimumab and investigated the clinical factors associated with a good response in primary tumors.
We retrospectively assessed 27 patients diagnosed with advanced renal cell carcinoma (RCC) who started treatment with nivolumab plus ipilimumab. Changes in tumor sizes at the primary site were described using waterfall and spider plots, respectively. We analyzed the correlation of tumor shrinkage between primary and metastatic site. The parameters analyzed between responders and non-responders according to primary tumor sizes were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers, and CRP.
The median age and follow-up period were 66 years and 9.3 months, respectively. The median IMDC risk score was 3 (range: 1-6). Nineteen patients were diagnosed with clear-cell RCC (ccRCC) and 8 patients with non-ccRCC. Among ccRCC patients, 9 (47.4%) achieved a significant response with a maximum reduction of 30% or more in the size of the primary tumor from baseline within 4 months, while 3 (37.5%) out of 8 patients with non-ccRCC achieved a significant response. Shrinkage of the primary tumor correlated with the metastatic tumors in both ccRCC and non-ccRCC cases. Of note, 6 patients underwent CN and no viable tumor cells were detected in the surgical specimens of 3 patients whose primary tumors shrank by approximately 50%-60% with a reduction to 4 cm or less. Among ccRCC patients, the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were slightly lower in responders than in non-responders (P = 0.0944 and P = 0.0691). The platelet-to-lymphocyte ratio was significantly lower in responders than in non-responder (P = 0.0391).
Significant responses in primary tumors to nivolumab plus ipilimumab were observed in 50% of ccRCC patients, while responses varied among non-ccRCC patients. Inflammation markers may be predictive factors of treatment responses in primary tumors. Although further studies are needed, the present results suggest the importance of considering CN from radiological and pathological viewpoints.
随着几种有效联合疗法的出现，关于其在原发部位疗效的信息对于规划未来的减瘤性肾切除术（CN）至关重要。本研究专门关注纳武利尤单抗联合伊匹单抗治疗后原发肿瘤大小的变化，并探讨了与原发肿瘤良好反应相关的临床因素。
我们回顾性评估了 27 例诊断为晚期肾细胞癌（RCC）并开始接受纳武利尤单抗联合伊匹单抗治疗的患者。分别使用瀑布图和蜘蛛图描述原发部位肿瘤大小的变化。我们分析了原发和转移部位肿瘤缩小之间的相关性。根据原发肿瘤大小，我们对有反应者和无反应者进行了分析的参数包括国际转移性肾细胞癌数据库联盟（IMDC）风险评分、外周血标志物和 CRP。
中位年龄和随访时间分别为 66 岁和 9.3 个月。中位 IMDC 风险评分为 3 分（范围：1-6）。19 例患者被诊断为透明细胞 RCC（ccRCC），8 例患者为非 ccRCC。在 ccRCC 患者中，有 9 例（47.4%）在 4 个月内从基线开始的原发肿瘤大小最大减少 30%或更多，达到显著缓解，而 8 例非 ccRCC 患者中有 3 例（37.5%）达到显著缓解。ccRCC 和非 ccRCC 患者的原发肿瘤缩小与转移肿瘤相关。值得注意的是，6 例患者接受了 CN，其中 3 例患者的原发肿瘤缩小约 50%-60%，缩小至 4cm 或更小，手术标本中未检测到存活的肿瘤细胞。在 ccRCC 患者中，与无反应者相比，反应者的中性粒细胞与淋巴细胞比值和单核细胞与淋巴细胞比值略低（P=0.0944 和 P=0.0691）。反应者的血小板与淋巴细胞比值明显低于无反应者（P=0.0391）。
纳武利尤单抗联合伊匹单抗治疗后，ccRCC 患者中有 50%的患者原发肿瘤出现显著缓解，而非 ccRCC 患者的缓解情况各不相同。炎症标志物可能是预测原发肿瘤治疗反应的因素。尽管需要进一步的研究，但目前的结果表明，从影像学和病理学角度考虑 CN 的重要性。
