Gastrointestinal Tumor Study Group 9173

Background

Phase III RCT (Gastrointestinal Tumor Study Group 9173). 43 patients with resected pancreatic adenocarcinoma randomized 1:1 to adjuvant chemoradiotherapy (40 Gy split-course + 5-FU bolus) or observation. This was the landmark trial establishing a potential role for adjuvant CRT in resected pancreatic cancer.

Interventions and follow up

Arm A: Adjuvant 5-FU 500 mg/m² bolus days 1–3 + 40 Gy split-course RT (2 × 20 Gy with 2-week break) + maintenance 5-FU weekly × 2 year
Arm B: Surgery alone (observation)
Primary endpoint: Overall survival

Results

mOS: 20 months (CRT) vs 11 months (observation), P=.03
2-yr OS: 42% vs 15%

Adverse events

Main adverse events: Nausea, vomiting, and myelosuppression with 5-FU; split-course RT was generally tolerable. No treatment-related deaths reported.

Conclusions

Adjuvant CRT significantly improved OS compared to observation in resected pancreatic cancer (20 vs 11 months), establishing the concept that adjuvant therapy benefits this disease. This was the first RCT to demonstrate a survival advantage for adjuvant treatment in resected pancreatic cancer.

Key Limitations

Key Limitations: Extremely small trial (n=43) — underpowered and potentially subject to chance findings. Split-course RT technique is obsolete. 5-FU alone as radiosensitizer is suboptimal by modern standards. No quality-of-life data. Three patients died during treatment in the CRT arm. Results were not reproducible in European trials (ESPAC-1), which showed adjuvant CRT was detrimental.

Clinical Context

GITSG 9173 influenced US practice for years despite its small size. Subsequent EORTC and ESPAC-1 trials failed to confirm a CRT benefit; ESPAC-1 found CRT was actually harmful. The field has since shifted toward systemic chemotherapy (CONKO-001, ESPAC-4, PRODIGE-24). Adjuvant CRT remains controversial and is generally not standard outside selected borderline resection margin-positive cases.

References

References: Kalser MH et al, Arch Surg 1985 (GITSG 9173)