Background
Phase III RCT (GOG 122). 396 patients with stage III-IV endometrial carcinoma (complete resection to ≤2 cm residual disease after TAH-BSO). Randomized to whole abdominal irradiation (WAI: 30 Gy whole abdomen with 15-Gy pelvic boost) vs doxorubicin + cisplatin (AP) chemotherapy (7 cycles + 1 additional cycle of cisplatin). First trial to demonstrate chemotherapy superiority to radiation therapy for advanced endometrial cancer.
Interventions and follow up
Arm A: Whole abdominal irradiation (WAI): 30 Gy whole abdomen + 15 Gy pelvic boost (total 45 Gy pelvis)
Arm B: Doxorubicin 60 mg/m² + cisplatin 50 mg/m² × 7 cycles (AP chemotherapy)
Primary endpoint: Progression-free survival (PFS) and OS
mFollow up: 74 month
Arm B: Doxorubicin 60 mg/m² + cisplatin 50 mg/m² × 7 cycles (AP chemotherapy)
Primary endpoint: Progression-free survival (PFS) and OS
mFollow up: 74 month
Results
5-year PFS: 38% (WAI) vs 50% (AP chemo), HR 0.71 (95% CI 0.55–0.91), P=.007
5-year OS: 42% (WAI) vs 55% (AP chemo), P=.004
Pelvic recurrence: Slightly lower with WAI; distant recurrence lower with AP chemo
5-year OS: 42% (WAI) vs 55% (AP chemo), P=.004
Pelvic recurrence: Slightly lower with WAI; distant recurrence lower with AP chemo
Adverse events
Main adverse events: Hematologic toxicity grade ≥3: 15% (WAI) vs 88% (AP chemo). GI toxicity grade ≥3: 14% (WAI) vs 12% (AP chemo). Grade ≥3 neurologic: 12% (AP chemo) vs 4% (WAI) — cisplatin peripheral neuropathy. Treatment-related deaths: 4 (WAI) vs 2 (AP chemo).
Conclusions
AP chemotherapy was superior to WAI in both PFS and OS for advanced (stage III-IV) endometrial cancer with ≤2 cm residual disease, establishing systemic chemotherapy as the primary adjuvant treatment for advanced endometrial cancer.
Key Limitations
Key Limitations: WAI is an outdated and toxic radiation technique — this comparison does not address modern pelvic IMRT or combined RT + chemotherapy. AP (doxorubicin + cisplatin) was the chemotherapy backbone — this has been largely replaced by carboplatin + paclitaxel (GOG 209, superior PFS/toxicity). Stage III patients included both nodal (IIIC) and serosal (IIIA/B) disease — heterogeneous outcomes. No OS crossover or salvage treatment analysis.
Clinical Context
GOG 122 established that chemotherapy is superior to WAI for advanced endometrial cancer. AP chemotherapy was subsequently replaced by carboplatin + paclitaxel (GOG 209: equivalent efficacy, better toxicity). Modern advanced endometrial cancer management uses carboplatin + paclitaxel ± pembrolizumab (RUBY, NRG GY018) with pelvic RT for locoregional control. GOG 258 addressed the optimal RT + CT integration for stage III.
References
References: Randall ME et al, J Clin Oncol 2006 (GOG 122)