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PubMed This is a summary of 15 peer-reviewed journal articles Updated
Oncology

Why Chemo Before Surgery for Diffuse Gastric Cancer?

At a Glance

Chemotherapy is given before surgery for diffuse gastric cancer to destroy microscopic cancer cells that have spread beyond the stomach and to shrink the main tumor. This approach increases the chance of entirely removing the cancer and significantly improves long-term survival.

In this answer

4 sections

01

1. Destroying “Hidden” Cancer Cells

02

2. Shrinking the Tumor for a Safer, Cleaner Surgery

03

The Standard Treatment Timeline: The FLOT Regimen

04

A Note on Diffuse-Type Gastric Cancer

When you are diagnosed with locally advanced diffuse gastric adenocarcinoma—meaning the cancer has grown deeply into the stomach wall or nearby lymph nodes but hasn’t spread to distant organs—it is completely normal to feel an overwhelming urge to have surgery right away. Many people wonder, “If the scans show the cancer is only in my stomach, why can’t we just cut it out immediately?”

The reason for delaying surgery is based on a standard treatment strategy called perioperative chemotherapy (chemotherapy given both before and after surgery). Having chemotherapy first significantly improves your chances of long-term survival and a successful surgery compared to going straight to the operating room [1][2].

There are two primary reasons why your care team recommends this approach:

1. Destroying “Hidden” Cancer Cells

Even if your CT or PET scans look entirely clear outside the stomach, cancer cells are microscopic. Micrometastases are tiny, stray cancer cells that may have already broken away from the main stomach tumor and entered your bloodstream, lymphatic system, or the lining of your abdomen (peritoneum) [3][4]. Diffuse gastric cancer is particularly prone to early, microscopic spread.

Because these cells are too small to be seen on any imaging scan, surgery alone cannot guarantee they are completely removed. If left behind, they can grow and cause the cancer to return (recurrence) months or years later. Chemotherapy travels throughout your entire body to hunt down and destroy these micrometastases before they have a chance to take root [5][6].

2. Shrinking the Tumor for a Safer, Cleaner Surgery

The second goal of chemotherapy before surgery (also called neoadjuvant chemotherapy) is to shrink the primary tumor in your stomach. Diffuse gastric cancer tends to spread outward through the stomach wall like a web, making its exact borders difficult to see.

By shrinking the tumor first, chemotherapy increases the likelihood of an R0 resection [5][7]. An R0 resection is a surgical term meaning the surgeon was able to remove the entire tumor with clean margins, leaving absolutely no cancer cells behind at the edges of the removed tissue. Achieving an R0 resection is one of the most important factors for long-term survival [8].

The Standard Treatment Timeline: The FLOT Regimen

For most patients strong enough to tolerate it, the standard chemotherapy used before surgery is the FLOT regimen [9][10]. FLOT is an acronym for the four drugs involved:

  • Fluorouracil (5-FU)
  • Leucovorin
  • Oxaliplatin
  • Taxotere (the brand name for the taxane drug docetaxel)

What is the timeline? A standard course of FLOT involves 4 cycles of treatment before surgery, which takes about 8 weeks to complete. After you recover from surgery, you typically complete another 4 cycles (8 more weeks) [9][11]. While the focus is on shrinking the tumor, your care team will also provide supportive medications to help manage side effects, such as nausea or fatigue, during these weeks.

A Note on Diffuse-Type Gastric Cancer

It is important to know that diffuse gastric adenocarcinoma, particularly if it contains signet ring cells, behaves a bit differently than other types of stomach cancer. While perioperative chemotherapy remains the standard recommendation to maximize your chances of a cure [12][13], some research suggests that diffuse-type cancers might not shrink as dramatically in response to chemotherapy as other types do [14][15].

Because of this nuance, your multidisciplinary team will monitor you closely during your 8 weeks of preoperative treatment. This monitoring often involves repeating a CT scan or endoscopy midway through treatment, and checking your symptoms, to ensure the tumor is not growing. If the cancer does not appear to be responding to the chemotherapy, your care team can pivot their strategy and move you to surgery sooner than originally planned. You are never left without a backup plan.

Common questions in this guide

Why can't I just have surgery immediately for my stomach cancer?
While it is natural to want the tumor removed immediately, giving chemotherapy first helps destroy hidden cancer cells and shrinks the main tumor. This significantly improves your overall chances of a successful surgery and long-term survival compared to surgery alone.
What is the FLOT regimen and how long does it take?
FLOT is a standard chemotherapy combination containing four drugs: Fluorouracil, Leucovorin, Oxaliplatin, and Taxotere. Treatment typically involves four cycles (about 8 weeks) before surgery, followed by another four cycles after you recover from the operation.
How will my doctor know if the chemotherapy is actually shrinking the tumor?
Your multidisciplinary team will monitor your symptoms and typically perform a repeat CT scan or endoscopy midway through your treatment. This helps them confirm that the tumor is not growing and is responding to the drugs.
What happens if my cancer doesn't shrink during chemotherapy?
Diffuse-type gastric cancers sometimes do not shrink as dramatically as other types. If your mid-treatment scans show the tumor is not responding to the chemotherapy, your care team has a backup plan and can move you to surgery sooner than originally scheduled.
How do I stay strong enough for surgery while going through chemotherapy?
Your care team will provide supportive medications to help manage side effects like nausea and fatigue. Working with an oncology dietitian and relying on a support system can also help you maintain your nutrition and strength prior to the operation.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is the specific timeline for my preoperative chemotherapy, and how long after finishing will my surgery be scheduled?
  2. 2.How will we monitor whether my diffuse-type tumor is actually shrinking or responding during the weeks I am receiving chemotherapy?
  3. 3.If my mid-treatment scans show the tumor is not responding to the FLOT regimen, what is our immediate backup plan?
  4. 4.How do we manage severe side effects so that I don't lose too much strength before the operation?
  5. 5.Does my biopsy show 'signet ring cells', and if so, how does that factor into your recommendation for perioperative chemotherapy?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

Related questions

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References

References (15)
  1. 1

    Real-life data on improvement of survival after perioperative chemotherapy versus surgery alone on resectable adenocarcinoma of the stomach - a single-center study.

    Kuhnle PJ, Israel KF, Menges M

    Zeitschrift fur Gastroenterologie 2019; (57(5)):606-610 doi:10.1055/a-0841-3513.

    PMID: 31083749
  2. 2

    Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis.

    Zhao JH, Gao P, Song YX, et al.

    BMC cancer 2016; (16()):631 doi:10.1186/s12885-016-2667-5.

    PMID: 27519527
  3. 3

    Efficacy of neoadjuvant chemotherapy combined with prophylactic intraperitoneal hyperthermic chemotherapy for patients diagnosed with clinical T4 gastric cancer who underwent laparoscopic radical gastrectomy: a retrospective cohort study based on propensity score matching.

    Lv CB, Tong LY, Zeng WM, et al.

    World journal of surgical oncology 2024; (22(1)):244 doi:10.1186/s12957-024-03526-y.

    PMID: 39256787
  4. 4

    Neoadjuvant Therapies for Patients with Locally Advanced Gastric Cancer: A Retrospective Cohort Study.

    Ağırman E, Albayrak Y, Peksöz R, et al.

    The Eurasian journal of medicine 2024; (56(2)):121-126 doi:10.5152/eurasianjmed.2024.24468.

    PMID: 41340463
  5. 5

    Gastric cancer: histological response of tumor and metastatic lymph nodes for perioperative chemotherapy.

    Fonseca T, Coimbra M, Barbosa E, Barbosa J

    Cirugia y cirujanos 2022; (90(S2)):36-41 doi:10.24875/CIRU.21000657.

    PMID: 36480751
  6. 6

    Naples Prognostic Score Predicts Tumor Regression Grade in Resectable Gastric Cancer Treated with Preoperative Chemotherapy.

    Lieto E, Auricchio A, Tirino G, et al.

    Cancers 2021; (13(18)) doi:10.3390/cancers13184676.

    PMID: 34572903
  7. 7

    Perioperative immunotherapy in gastric cancer in the spotlight.

    Pernomian LS, Teixeira MF, Araujo RL, Serrano Uson Junior PL

    World journal of clinical oncology 2025; (16(12)):110988 doi:10.5306/wjco.v16.i12.110988.

    PMID: 41480178
  8. 8

    Perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) for esophagogastric adenocarcinoma: ten years real-life experience from a surgical perspective.

    Sisic L, Crnovrsanin N, Nienhueser H, et al.

    Langenbeck's archives of surgery 2023; (408(1)):81 doi:10.1007/s00423-023-02822-7.

    PMID: 36763220
  9. 9

    Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.

    Al-Batran SE, Homann N, Pauligk C, et al.

    Lancet (London, England) 2019; (393(10184)):1948-1957 doi:10.1016/S0140-6736(18)32557-1.

    PMID: 30982686
  10. 10

    The Landmark Series: Neoadjuvant Therapy for Patients with Resectable Gastroesophageal Junction Adenocarcinomas.

    Pettigrew MF, Coburn NG, Woo Y, Porembka MR

    Annals of surgical oncology 2026; doi:10.1245/s10434-026-20114-4.

    PMID: 42414817
  11. 11

    [Does the FLOT regimen a new standard of perioperative chemotherapy for localized gastric cancer?]

    Adenis A, Samalin E, Mazard T, et al.

    Bulletin du cancer 2020; (107(1)):54-60 doi:10.1016/j.bulcan.2019.12.005.

    PMID: 31980145
  12. 12

    Perioperative chemotherapy improves survival of patients with locally advanced diffuse gastric cancer.

    Li ZF, Li Z, Zhang XJ, et al.

    World journal of gastrointestinal surgery 2024; (16(9)):2878-2892 doi:10.4240/wjgs.v16.i9.2878.

    PMID: 39351555
  13. 13

    Effectiveness of Neoadjuvant Chemotherapy With Docetaxel, Cisplatin, and S-1 for Locoregionally Advanced Gastric Adenocarcinoma: Findings From a University Hospital in Vietnam.

    Tran TV, Thai TT, La LN, et al.

    Asia-Pacific journal of clinical oncology 2025; doi:10.1111/ajco.70039.

    PMID: 41122959
  14. 14

    Neoadjuvant chemotherapy for Lauren diffuse-type gastric cancer: Is it necessary?

    Lai B, Xiong Z, Zhong B, et al.

    European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2026; (52(5)):111767 doi:10.1016/j.ejso.2026.111767.

    PMID: 41894922
  15. 15

    Upfront surgery versus chemotherapy neoadjuvant in the survival of patients with locally advanced gastric signet-ring-cell adenocarcinoma. A scoping review.

    Vásquez-Jaico ER, Yan-Quiroz EF, Bonilla-Feria N, et al.

    Ecancermedicalscience 2025; (19()):1843 doi:10.3332/ecancer.2025.1843.

    PMID: 40248270

This page provides general information about preoperative chemotherapy for diffuse gastric cancer. Always consult your oncology team to determine the best treatment plan and timeline for your specific diagnosis.

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