Mizuno Taro, Narita Yukiya, Ishizuka Yasunobu, Sakakida Tomoki, Honda Kazunori, Masuishi Toshiki, Taniguchi Hiroya, Kadowaki Shigenori, Ando Masashi, Tajika Masahiro, Muro Kei
Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya, Aichi, 464-8681, Japan.
Department of Endoscopy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya, Aichi, 464-8681, Japan.
J Cancer Res Clin Oncol. 2025 Jul 8;151(7):206. doi: 10.1007/s00432-025-06255-1.
Programmed cell death ligand 1 (PD-L1) expression in advanced gastric cancer (AGC) exhibits spatial heterogeneity, which may lead to sampling bias during biopsies. Although multiple biopsies are believed to improve the accuracy of PD-L1 assessment, the optimal number of specimens remains uncertain. This study investigated the relationship between PD-L1 expression and biopsy specimen count in AGC.
We retrospectively analyzed 110 patients with AGC who underwent first-line chemotherapy and had PD-L1 combined positive scores (CPS) assessed using the 28-8 pharmDx assay. Associations between CPS and biopsy specimen count were evaluated using chi-square or Fisher's exact test. In a subgroup of 70 human epidermal growth factor receptor 2 (HER2)-negative patients treated with first-line nivolumab plus chemotherapy, survival outcomes were analyzed based on CPS status.
PD-L1 CPS ≥ 5 was identified in 79 patients (71.8%). The proportion of patients with CPS ≥ 5 was significantly higher in those with ≥ 5 biopsy specimens than in those with ≤ 4 (77.5% vs. 56.7%, P = 0.03). This trend was even more pronounced in HER2-negative patients (83.6% vs. 54.5%, P < 0.01) and in those with macroscopic type 2 tumors (91.3% vs. 33.3%, P < 0.01). However, no significant differences in progression-free or overall survival were found based on CPS status, regardless of biopsy count.
Obtaining at least five biopsy specimens enhances the detection of PD-L1 CPS ≥ 5, particularly in HER2-negative or well-circumscribed nodular AGC, potentially improving the accuracy of PD-L1 evaluation. Nevertheless, survival outcomes were unaffected, highlighting the limited predictive value of CPS.
晚期胃癌（AGC）中程序性细胞死亡配体1（PD-L1）表达呈现空间异质性，这可能导致活检过程中出现取样偏差。尽管认为多次活检可提高PD-L1评估的准确性，但最佳标本数量仍不确定。本研究调查了AGC中PD-L1表达与活检标本数量之间的关系。
我们回顾性分析了110例接受一线化疗且使用28-8 pharmDx检测法评估了PD-L1联合阳性评分（CPS）的AGC患者。使用卡方检验或Fisher精确检验评估CPS与活检标本数量之间的关联。在70例接受一线纳武单抗联合化疗的人表皮生长因子受体2（HER2）阴性患者亚组中，根据CPS状态分析生存结局。
79例患者（71.8%）的PD-L1 CPS≥5。活检标本≥5份的患者中CPS≥5的比例显著高于活检标本≤4份的患者（77.5%对56.7%，P = 0.03）。这种趋势在HER2阴性患者中更为明显（83.6%对54.5%，P < 0.01），在大体类型为2型肿瘤的患者中也是如此（91.3%对33.3%，P < 0.01）。然而，无论活检数量如何，基于CPS状态的无进展生存期或总生存期均未发现显著差异。
获取至少五份活检标本可提高PD-L1 CPS≥5的检测率，特别是在HER2阴性或边界清楚的结节状AGC中，可能提高PD-L1评估的准确性。然而，生存结局未受影响，突出了CPS的预测价值有限。
