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. 2025 Sep;28(5):982-992.
doi: 10.1007/s10120-025-01624-8. Epub 2025 May 16.

Impact of adjuvant therapy on outcomes of cancer of the stomach and gastroesophageal junction in the real-world

Steffen M Heckl  1   2 , Hans-Michael Behrens #  1 , Ulrike Ebert #  1 , Dita Ulase  1 , Florian Richter  3 , Thomas Becker  3 , Anne Letsch  2 , Christoph Röcken  4
Affiliations

Impact of adjuvant therapy on outcomes of cancer of the stomach and gastroesophageal junction in the real-world

Steffen M Heckl et al. Gastric Cancer. 2025 Sep.

Abstract

Background: Since the FLOT4 gastric cancer (GC) trial, the use of adjuvant chemotherapy has been perceived as limited and its added value questioned. We wanted to objectify this perception and reassess the value of adjuvant chemotherapy in a real-world setting.

Methods: In our retrospective cohort study we analyzed real-world data from 147 patients with GC or cancer of the gastroesophageal junction (AEG) who received perioperative FLOT. Data originated from clinical care at the university hospital, local hospitals and medical practices. Clinicopathologic data, survival outcomes, and targetable biomarkers were analyzed.

Results: Median overall survival (OS) and tumor specific survival (TSS) were 19.4 ± 2.9 and 19.9 ± 3.1 months, respectively. 84.4% completed all cycles of neoadjuvant chemotherapy. The pathological complete response rate was 11.8%. Adjuvant chemotherapy was initiated in only 42.9%. Survival rates of patients with marked tumor regression (TRG1) were not improved by adjuvant chemotherapy. Conversely, patients with partial histopathologic response (TRG2) showed a marked trend and those with minimal histopathologic response (TRG3) showed a significantly longer survival with any number of adjuvant chemotherapy cycles (OS: 22.3 ± 2.6 months versus 8.7 ± 2.4 months, p = 0.005; TSS: 22.3 ± 4.5 months versus 8.7 ± 2.4 months, p = 0.016). Targetable biomarkers PD-L1, Claudin 18.2, HER2 and microsatellite instability were detected in 53.4%, 26.2%, 7.8%, and 3.9% of the TRG2/3 patient subset, respectively.

Conclusions: In the real-world setting, adjuvant chemotherapy proved to be a critical turning point of the FLOT regimen. It should be sought-even in a reduced form-in patients with TRG2/3.

Keywords: Adjuvant; Biomarkers; Chemotherapy; Esophagogastric junction; Gastric cancer.

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Conflict of interest statement

Declarations. Conflict of interest: AL received payment or honoraria from Astra Zeneca, Bayer, BMS, Böhringer Ingelheim, Grünenthal, Janssen, Lilly, MSD, Novartis, Roche, Servier and Tesaro. AL participates on the advisory boards of MSD, BMS and Lilly. AL has a leadership role in the Board of Directors European Association of Palliative Care (2023–2026) and in the ESMO Supportive and Palliative Care Faculty (2023–2026). All other authors declare no competing interests. Ethical approval: All procedures followed were in accordance with the ethical standards of the ethics committee [D453/10 (22.10.2010); D525/15 (20.08.2015)] of the University Hospital Schleswig–Holstein, Kiel, Germany, which allowed us to use samples from those patients who had also given written informed consent for prospective scientific use of their patient material (broad consent). The study was performed in compliance with all relevant laws and institutional guidelines and in accordance with the code of ethics of the Helsinki Declaration of 1964 and later versions.

Figures

Fig. 1
Fig. 1
Patients screening. Description of the patient screening process. We screened 311 patients of the FLOT era and identified 147 patients who had received perioperative chemotherapy with FLOT
Fig. 2
Fig. 2
Waterfall plot depicting the neoadjuvant (blue bars) and adjuvant (red bars). Administration of perioperative chemotherapy with FLOT in the real-world study cohort. Indicated blue bar = patient received no neoadjuvant chemotherapy. Indicated red bar = patient received no adjuvant chemotherapy. No indicated red bar = no patient data about the adjuvant phase available. No indicated blue bar = no patient data about the neoadjuvant phase available. The tumor regression grades (TRG) are highlighted with colors, with TRG1, TRG2, TRG3 being represented by the colors green, yellow and red, respectively. Complete data about the neoadjuvant phase was available from 141 (95.9%) of 147 patients of the FLOT group. As three patients had not received neoadjuvant chemotherapy, the TRG was not applicable for these cases
Fig. 3
Fig. 3
Kaplan–Meier estimates of overall (a) and tumor-specific (b) survivals. a, b: Comparison of histopathologic tumor regression (TRG) according to Becker
Fig. 4
Fig. 4
Kaplan–Meier estimates of overall (a, c, e) and tumor-specific (b, d, f) survivals. a, b: Comparison of adjuvant chemotherapy versus no adjuvant chemotherapy in patients with TRG1a/b. c, d: Comparison of adjuvant chemotherapy versus no adjuvant chemotherapy in patients with TRG2. e, f: Comparison of adjuvant chemotherapy versus no adjuvant chemotherapy in patients with TRG3
Fig. 5
Fig. 5
Distribution of targetable biomarkers in the TRG2/3 patient subgroup. UpSet plot showing the distribution of the targetable biomarkers PD-L1, Claudin 18.2 and HER2 as well as the MSI (microsatellite instability) status of the 103 TRG2/3 patients. PD-L1 expression with combined positive scores (CPS) of 1–4, 5–9 and ≥ 10 were observed in 20 (19.4%), 12 (11.7%) and 23 (22.3%) patients, respectively. The biomarkers HER2 and Claudin 18.2 were expressed in 8 (7.8%) and 27 (26.2%) patients of the TRG2/3 patient subset, respectively. We identified 4 patients (3.9%) with MSI tumors. Biomarker co-expression is visualized with connecting bars and enumerated in the upper part of the illustration
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