When do you start chemotherapy for a patient with newly diagnosed gastric cancer in relation to surgery?

Timing of Chemotherapy for Gastric Cancer

For resectable gastric cancer stage IB and above, start chemotherapy immediately after diagnosis and staging workup is complete, before surgery—this perioperative approach with 3 preoperative cycles followed by surgery then 3 postoperative cycles is the standard of care. 1, 2

Staging Workup Before Treatment Initiation

Complete the following staging within 2-3 weeks of diagnosis before starting any treatment:

• Endoscopy with biopsy for histological confirmation, Lauren classification, and HER2 testing 1, 2
• CT chest, abdomen, and pelvis to assess resectability and detect metastases 1
• Laparoscopy with peritoneal washings for all stage IB-III disease to exclude occult peritoneal metastases that imaging misses 1, 2
• Blood counts, liver and renal function tests 1

Treatment Algorithm by Stage

Very Early Disease (T1a, Stage 0-IA)

• Endoscopic resection alone if tumor is well-differentiated, ≤2 cm, confined to mucosa, non-ulcerated, and no lymphovascular invasion 1, 2
• No chemotherapy needed for these patients 3

Resectable Locoregional Disease (Stage IB-III)

Start perioperative chemotherapy immediately after staging:

• 3 cycles of preoperative chemotherapy using ECF (epirubicin 50 mg/m² D1, cisplatin 60 mg/m² D1, 5-FU 200 mg/m²/day D1-21 every 21 days) or ECX (substituting capecitabine for 5-FU) 1, 2
• Surgery performed 3-4 weeks after completing preoperative chemotherapy 1
• 3 additional postoperative cycles of the same regimen to complete 6 total cycles 1, 2

This perioperative approach improved 5-year survival from 23% to 36% in the MAGIC trial (hazard ratio 0.75), with similar results confirmed in the French FNCLCC/FFCD trial 1, 2. This is the European standard of care with Level I, Grade A evidence. 1

Alternative: Postoperative Chemoradiation (North American Approach)

If surgery is performed first without preoperative chemotherapy:

• Start adjuvant chemoradiation within 4-6 weeks post-surgery for stage IB or higher 1
• 5 cycles of 5-FU/leucovorin with concurrent radiotherapy (45 Gy in 25 fractions) during cycles 2 and 3 1
• This approach showed 15% survival advantage at 4-5 years (hazard ratio 1.32 at 10 years) 1

Critical caveat: This approach is primarily used when preoperative chemotherapy was not given, and is most beneficial after suboptimal (D1 or less) lymphadenectomy 1. After adequate D2 resection, the benefit is less clear 1.

Metastatic Disease (Stage IV)

Start palliative chemotherapy immediately for patients with good performance status (ECOG 0-2):

• First-line: Platinum/fluoropyrimidine doublet or triplet regimens (ECF, DCF, or FLOT) 1, 2, 4
• Add trastuzumab if HER2-positive (IHC 3+ or IHC 2+/FISH+), which improves median survival from 11.1 to 13.8 months 1, 4
• Chemotherapy extends median survival from 5 months (best supportive care alone) to 8 months 4

Common Pitfalls to Avoid

Do not proceed directly to surgery without laparoscopy in stage IB-III disease—imaging misses peritoneal metastases in a significant proportion of patients, and discovering these at laparotomy wastes the opportunity for preoperative chemotherapy 1, 2

Do not delay chemotherapy for prolonged nutritional optimization—start treatment within 2-3 weeks of completing staging, as delays worsen outcomes 2, 4

Do not use postoperative chemotherapy alone (without radiation) as standard adjuvant treatment in Western populations, as individual trials have failed to show survival benefit and toxicity is considerable in the postoperative setting 1. The perioperative approach is superior because preoperative chemotherapy is better tolerated 1.

Do not forget HER2 testing in potentially metastatic disease—failure to test means missing a 2.7-month survival advantage with trastuzumab 4

Timeline Summary

• Days 1-14: Complete staging workup including laparoscopy
• Days 15-21: Multidisciplinary team discussion and treatment planning 1, 2
• Day 21-28: Start first cycle of preoperative chemotherapy
• Week 10-11: Complete 3 preoperative cycles
• Week 13-14: Surgery (3-4 weeks after last chemotherapy cycle)
• Week 18-20: Start postoperative chemotherapy (4-6 weeks post-surgery)
• Week 27-28: Complete all 6 cycles of perioperative chemotherapy