Gallanis Amber F, Bowden Cassidy, Lopez Rachael, Fasaye Grace-Ann, Lang David, Rothschild Jill, Camargo M Constanza, Hernandez Jonathan M, Rai Anjali, Heller Theo, Blakely Andrew M, Davis Jeremy L
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
Clinical Center Nutrition Department, National Institutes of Health, Bethesda, MD 20892, United States.
J Natl Cancer Inst. 2025 May 1;117(5):1027-1035. doi: 10.1093/jnci/djaf002.
Adolescents and young adults (AYA) with germline CDH1 variants are at risk of overtreatment when precancer lesions are detected with endoscopic screening. We characterize diffuse-type gastric cancer prevalence and survival in AYA managed with prophylactic total gastrectomy (PTG) or endoscopic surveillance.
Prospective cohort study of 188 individuals aged 39 and younger enrolled from January 27, 2017, to May 1, 2023. Clinicopathological data, prevalence of early gastric signet ring cell (SRC) lesions, advanced gastric cancer diagnoses, and cancer-specific survival were measured.
Among 188 AYA patients, 104 chose surveillance and 67 pursued PTG for management of elevated gastric cancer risk. AYA who enrolled early in the study period and had SRC lesions detected on preoperative endoscopy were more likely to elect for PTG compared with surveillance. SRC lesions were detected on preoperative endoscopy in 48% of patients who subsequently had PTG, and yet nearly all (93%, 62/67) had multifocal SRC (pT1aN0) on final pathology. Median age at enrollment (30 vs 31 years, P = .21), biological sex (P = .17), and median number of family members with gastric cancer (3 vs 4, P = .14) were not different between groups. No patients under surveillance developed advanced cancer or developed cancer recurrence after PTG with a median follow-up of 2.5 years (IQR = 1.6-4.0) from initial endoscopy.
Cancer-specific outcomes were not different in AYA who harbored SRC and were managed with surveillance or PTG. Lack of cancer-specific deaths and low prevalence of advanced gastric cancer underscore the risk of overtreatment of SRC lesions and suggest that active surveillance is warranted.
携带种系CDH1变异的青少年和青年（AYA）在通过内镜筛查发现癌前病变时存在过度治疗的风险。我们对接受预防性全胃切除术（PTG）或内镜监测的AYA患者的弥漫型胃癌患病率和生存率进行了描述。
对2017年1月27日至2023年5月1日登记的188名39岁及以下个体进行前瞻性队列研究。测量临床病理数据、早期胃印戒细胞（SRC）病变的患病率、晚期胃癌诊断情况以及癌症特异性生存率。
在188名AYA患者中，104人选择监测，67人接受PTG以管理胃癌风险升高的情况。与监测相比，在研究早期入组且术前内镜检查发现有SRC病变的AYA更有可能选择PTG。在随后接受PTG的患者中，48%的患者术前内镜检查发现有SRC病变，但几乎所有患者（93%，62/67）最终病理显示为多灶性SRC（pT1aN0）。两组之间的入组时中位年龄（30岁对31岁，P = 0.21）、生物学性别（P = 0.17）以及胃癌家族成员的中位数量（3对4，P = 0.14）没有差异。中位随访时间为自初次内镜检查起2.5年（IQR = 1.6 - 4.0），接受监测的患者中没有出现晚期癌症，接受PTG的患者也没有出现癌症复发。
携带SRC且接受监测或PTG治疗的AYA患者的癌症特异性结局没有差异。缺乏癌症特异性死亡以及晚期胃癌的低患病率凸显了SRC病变过度治疗的风险，并表明进行主动监测是必要的。
