Background
Phase III RCT (GOG 92). 277 patients with stage IA2–IB cervical cancer who underwent radical hysterectomy and bilateral pelvic lymphadenectomy with negative lymph nodes but at intermediate risk of recurrence, defined by the Sedlis criteria (any 2 of: positive LVSI, deep stromal invasion ≥1/3, or tumor size ≥2 cm; subsequently modified to at least 2 or all 3 features). Enrolled 1988–1995.
Interventions and follow up
Arm A: Adjuvant pelvic radiation 46–50.4 Gy in 23–28 fractio
Arm B: Observation (no adjuvant therapy)
Primary endpoint: Recurrence-free survival
mFollow up: Median 71 month
Arm B: Observation (no adjuvant therapy)
Primary endpoint: Recurrence-free survival
mFollow up: Median 71 month
Results
2-year recurrence rate: 28% RT vs 44% observation
Recurrence risk reduction: HR ~0.54, approximately 46% relative risk reduction
OS: No statistically significant difference at initial reporting (mature OS data showed ~19% relative reduction in death with RT)
Recurrence risk reduction: HR ~0.54, approximately 46% relative risk reduction
OS: No statistically significant difference at initial reporting (mature OS data showed ~19% relative reduction in death with RT)
Adverse events
Main adverse events: Grade 3–4 gastrointestinal toxicity 2.1% RT vs 0% observation. Grade 3–4 genitourinary toxicity 0.7% vs 0%. No treatment-related deaths. Bowel obstruction requiring surgery was a rare but notable late toxicity.
Conclusions
Adjuvant pelvic radiation after radical hysterectomy significantly reduced recurrence rates in intermediate-risk cervical cancer, establishing postoperative RT as standard of care for patients meeting the Sedlis criteria. The magnitude of benefit supports adjuvant RT in this setting despite modest toxicity risk.
Key Limitations
Key Limitations: OS benefit was not statistically significant at initial reporting, and the trial was not powered for OS as primary endpoint. The Sedlis criteria for intermediate risk have since been applied variably across institutions. This trial predates the concurrent chemotherapy era; whether adding chemotherapy to adjuvant RT improves outcomes in intermediate-risk disease remains under investigation (NRG/GOG 0724 and STARS). Modern IMRT can further reduce late toxicity compared with the 4-field technique used in this trial.
Clinical Context
GOG 92 defines the "Sedlis criteria" for intermediate-risk cervical cancer and remains the foundational trial supporting adjuvant pelvic RT post-hysterectomy in node-negative disease. The complementary Peters trial (GOG 109) addresses high-risk disease (positive nodes, positive margins, or parametrial involvement), where concurrent cisplatin-based chemoradiation is the standard. Together, these two trials form the framework for postoperative cervical cancer management.
References
References: Sedlis A et al, Gynecol Oncol 1999 (GOG 92)