Abstract A074: Isolated pulmonary metastasis as the first site of progression predicts long-term overall survival in resected pancreatic adenocarcinoma
Kshitij S. Gaur, Shahmeer Mohydin, Bahda Yun, Mohammad Aldakkak, Filip Saitis, Aaron Kleinertz, Paul Linsky, Mandana Kamgar, Alexandra Phan, Janice Zhao, William Hall, Beth Erickson, Christina Small-Tom, Callisia Clarke, Kathleen Christians, Douglas Evans, Yongwoo David. SeoAbstract
Background:
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid malignancies, and metastatic disease has historically been treated as a homogeneous entity regardless of anatomic site, despite emerging evidence that the site of metastasis may reflect distinct tumor biology. We evaluated whether isolated pulmonary metastasis (IPM) as the first site of recurrence predicts survival after curative-intent resection.
Methods:
We retrospectively analyzed 451 consecutive patients with localized PDAC who completed neoadjuvant therapy and curative-intent resection at a single institution (2008-2024) and subsequently developed metastatic recurrence, stratifying patients by first documented site of recurrence. Overall survival (OS) and progression-free survival (PFS) were measured from resection using Kaplan-Meier estimates, log-rank tests, and multivariable Cox proportional hazards regression; landmark analyses among patients alive at 6, 9, 12, and 15 months after first progression were performed to account for immortal-time bias.
Results:
Of the cohort, 103 patients (22.8%) had lung as the first site of progression (IPM), while 348 (77.2%) recurred first at non-pulmonary or multiple sites (liver n=93, local n=60, peritoneum n=54, multi-site n=125). Median PFS was 18.1 months (95% CI, 15.9-22.8) for lung-first versus 8.6 months (7.7-9.3) for other sites (P<0.001), and median OS was 24.7 months (22.1-30.2) versus 10.3 months (9.2-11.3; P<0.001). This survival advantage persisted even when a second site developed after an initial lung recurrence (median OS, 28.8 months) compared with liver-first disease (10.1-10.7 months; P<0.0001). In landmark analyses (n=91, 82, 71, and 65 at 6, 9, 12, and 15 months, respectively), development of a second metastatic site after an initial lung recurrence was not significantly associated with overall survival at any landmark (adjusted HR range, 1.41-2.66; all P>0.05), indicating that the favorable prognosis of lung-first recurrence is not explained by lead-time effects. Among patients with pulmonary recurrence, surgical wedge resection with or without systemic therapy produced the best OS (28.8 months) relative to chemotherapy alone (24.3), radiotherapy (25.1), or observation (12.7 months; P=0.042).
Conclusion:
In resected PDAC, IPM as the first site of progression identifies a biologically indolent phenotype with markedly prolonged survival that persists despite subsequent metastatic spread. First site of recurrence may provide greater prognostic value than timing of recurrence, and selected patients with lung-first recurrence may benefit from aggressive local-regional therapy.
Citation Format:
Kshitij S. Gaur, Shahmeer Mohydin, Bahda Yun, Mohammad Aldakkak, Filip Saitis, Aaron Kleinertz, Paul Linsky, Mandana Kamgar, Alexandra Phan, Janice Zhao, William Hall, Beth Erickson, Christina Small-Tom, Callisia Clarke, Kathleen Christians, Douglas Evans, Yongwoo David. Seo. Isolated pulmonary metastasis as the first site of progression predicts long-term overall survival in resected pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A074.