Department of Surgery, New York University Langone Health, New York, NY, USA.
Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
J Natl Cancer Inst. 2024 Nov 1;116(11):1791-1797. doi: 10.1093/jnci/djae166.
Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared with its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated.
Consecutive upfront surgery patients with IPMN-derived PDAC from 5 international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤0.5, T1b >0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were used to compare overall survival (OS). A multivariable Cox regression was used to determine hazard ratios (HRs) with confidence intervals (95% CIs).
Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1 margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95% CI = 126.0 to NR), 128.8 (98.3 to NR), 77.6 (48.3 to 108.2), and 31.4 (27.5 to 37.7) months, respectively (P < .001). OS decreased with increasing T-stage for all pairwise comparisons (all P < .05). After risk adjustment, older than age 65, elevated CA19-9, T1b [HR = 2.55 (1.22 to 5.32)], T1c [HR = 3.04 (1.60 to 5.76)], and T2-4 [HR = 3.41 (1.89 to 6.17)] compared with T1a, nodal positivity, R1 margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared with T1a (18.2%), T1b (23.9%), and T1c (36.1%, P < .001).
T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines.
与具有明显生物学差异的胰腺上皮内瘤变（PanIN）衍生的胰腺导管腺癌（PDAC）相比，导管内乳头状黏液性肿瘤（IPMN）衍生的 PDAC 可在更小的体积时被切除。因此，专家们提出了用于 IPMN 衍生的 PDAC 的 T1 亚分期。然而，这从未得到验证。
连续来自 5 个国际大容量中心的接受直接手术治疗的 IPMN 衍生 PDAC 患者，根据建议的 T1 亚分期分类（T1a≤0.5cm，T1b＞0.5cm 且≤1.0cm，和 T1c＞1.0cm 且≤2.0cm），使用侵袭性成分大小。采用 Kaplan-Meier 和对数秩检验比较总生存（OS）。采用多变量 Cox 回归确定危险比（HR）和置信区间（95%CI）。
在 747 例患者中，分别有 69 例（9.2%）、50 例（6.7%）、99 例（13.0%）和 531 例（71.1%）患者归入 T1a、T1b、T1c 和 T2-4 亚组。随着 T 分期的增加，CA19-9 升高、分级较差、淋巴结阳性、R1 切缘和管状亚型的比例增加。T1a、T1b、T1c 和 T2-4 亚组的中位 OS 分别为 159.0（95%CI=126.0 至 NR）、128.8（98.3 至 NR）、77.6（48.3 至 108.2）和 31.4（27.5 至 37.7）个月（P＜0.001）。所有两两比较均显示随着 T 分期的增加 OS 降低（均 P＜0.05）。经过风险调整后，年龄＞65 岁、CA19-9 升高、T1b（HR=2.55（1.22 至 5.32））、T1c（HR=3.04（1.60 至 5.76））和 T2-4（HR=3.41（1.89 至 6.17））与 T1a 相比，淋巴结阳性、R1 切缘和无辅助化疗与较差的 OS 相关。T2-4 肿瘤的疾病复发率（56.4%）明显高于 T1a（18.2%）、T1b（23.9%）和 T1c（36.1%）（P＜0.001）。
IPMN 衍生的 PDAC 的 T1 亚分期是有效的，具有显著的预后价值。T1 亚分期的进展与较差的组织病理学、生存和复发相关。建议将 T1 亚分期纳入未来的指南中。
