Basso Umberto, Facchinetti Antonella, Rossi Elisabetta, Maruzzo Marco, Conteduca Vincenza, Aieta Michele, Massari Francesco, Fraccon Anna Paola, Mucciarini Claudia, Sava Teodoro, Santoni Matteo, Pegoraro Cristina, Durante Emilia, Nicodemo Maurizio, Perin Alessandra, Bearz Alessandra, Gatti Carlo, Fiduccia Pasquale, Diminutto Alberto, Barile Carmen, De Giorgi Ugo, Zamarchi Rita, Zagonel Vittorina
Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy.
Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy.
Oncologist. 2021 Sep;26(9):740-750. doi: 10.1002/onco.13842. Epub 2021 Jun 17.
Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC).
We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression.
One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five.
We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC.
This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.
循环肿瘤细胞（CTC）与乳腺癌、结直肠癌、肺癌和前列腺癌患者的不良预后相关。关于肾细胞癌（RCC）的数据较少。
我们设计了一项多中心前瞻性观察性研究，以评估接受抗血管生成酪氨酸激酶抑制剂作为一线治疗方案的转移性RCC患者的CTC计数与无进展生存期（PFS）之间的相关性；总生存期（OS）和反应为次要目标。通过CellSearch系统在四个时间点对CTC进行计数：治疗第0天、第28天、第56天，然后在疾病进展时计数，或在无进展的情况下在12个月时计数。
195例符合条件的患者，中位年龄69岁，接受舒尼替尼治疗的占77.5%，接受帕唑帕尼治疗的占21%。基线时，46.7%的患者每毫升有一个或多个CTC（范围为1至263）。30例患者至少有3个CTC，其PFS中位数为5.8个月，其余患者为15个月（p = 0.002；风险比[HR]，1.99），多变量分析时与国际转移性RCC数据库联盟评分无关（HR，1.91；95%置信区间[CI]，1.16 - 3.14）。至少有3个CTC的患者估计OS较短，为13.8个月，而少于3个CTC的患者为52.8个月（p = 0.003；HR，1.99；多变量分析HR，1.67；95% CI，0.95 - 2.93）。基线CTC计数与反应无关；CTC测序计数大于或等于1、2、3、4或不相关。
我们提供的前瞻性证据表明，基线时存在3个或更多CTC与转移性RCC患者显著缩短的PFS和OS相关。
这项前瞻性研究评估了外周血中循环肿瘤细胞（CTC）的存在是否与转移性肾细胞癌（RCC）一线酪氨酸激酶抑制剂的活性相关。该研究表明，几乎一半的转移性RCC患者血液中至少有一个CTC，且那些至少有3个CTC的患者因RCC出现早期疾病进展和早期死亡的风险增加。有必要将CTC计数纳入转移性RCC的预后算法研究中。
