Phase III randomized trial | Gastrointestinal Tumor Study Group (GITSG) | Resected PDAC | Annals of Surgery 1985 **Kalser et al.** Marc H. Kalser Published in Annals of Surgery, 1985 [PubMed Link](https://pubmed.ncbi.nlm.nih.gov/4015380/) --- ### Essential Takeaway The GITSG trial was the first landmark randomized study to suggest a survival benefit from adjuvant 5-FU–based chemoradiation following pancreatic cancer resection. Despite its small sample size and methodological limitations, the study fundamentally shaped North American adjuvant PDAC treatment paradigms for decades and established the foundation for postoperative therapy in pancreatic cancer. --- ### Clinical Question Does adjuvant chemoradiation improve survival compared with observation alone after curative-intent resection of pancreatic adenocarcinoma? --- ### Population - Resected pancreatic adenocarcinoma - Curative-intent surgery - No distant metastatic disease Most patients underwent pancreaticoduodenectomy. --- ### Study Design #### Arm 1 — Observation - Surgery alone - No planned postoperative therapy #### Arm 2 — Adjuvant Chemoradiation - Split-course radiotherapy - Concurrent bolus 5-FU - Maintenance 5-FU afterward Radiation regimen: - 40 Gy split-course RT - Two-week treatment break midway through therapy --- ### Endpoints #### Primary Endpoint Overall survival (OS) #### Secondary Endpoints - Recurrence patterns - Treatment toxicity --- ### Key Results #### Overall Survival Median survival favored adjuvant chemoradiation: - Chemoradiation: - 20 months - Observation: - 11 months Estimated 2-year survival: - 43% vs 18% --- #### Recurrence Findings High recurrence rates remained common in both groups, highlighting the aggressive systemic biology of PDAC despite local therapy. --- ### Additional Findings #### Established Postoperative Therapy as Standard Prior to GITSG, surgery alone was generally considered the only meaningful treatment option for resected PDAC. The study helped establish the principle that postoperative multimodality therapy could improve outcomes after resection. #### Influenced North American Practice The trial strongly influenced decades of U.S. practice patterns favoring adjuvant chemoradiation following pancreatic resection. --- ### Interpretation GITSG became one of the foundational trials in pancreatic oncology because it introduced the concept of effective postoperative therapy after pancreatic resection. Although small and methodologically limited by modern standards, the trial significantly shifted treatment paradigms and established adjuvant therapy as a central component of PDAC management. The study also contributed to the long-standing divergence between: - North American CRT-focused strategies - European chemotherapy-focused approaches that later emerged in ESPAC-era trials. --- ### Important Limitations #### Small Sample Size - Limited enrollment - Trial closed early due to poor accrual #### Older Radiation Techniques - Split-course RT is no longer standard - Modern RT planning differs substantially #### Outdated Systemic Therapy - Bolus 5-FU regimen predates modern chemotherapy #### Historical Context - Conducted before modern staging - Conducted before contemporary surgical standards - Results interpreted differently in later international studies --- ### Practice Impact GITSG established postoperative therapy as an important component of PDAC treatment and strongly shaped North American use of adjuvant chemoradiation for many years. The trial served as the conceptual foundation for subsequent adjuvant studies including: - ESPAC - CONKO - RTOG - PRODIGE-24 It remains one of the most historically important trials in pancreatic cancer management.