Background
Phase III RCT (RTOG 9001). 403 patients with FIGO stage IB2–IVA cervical carcinoma (bulky IB ≥5 cm or stages IIB–IVA) treated at multiple institutions. Patients were randomized between pelvic chemoradiation and extended-field radiation (PA LNs included), reflecting the then-standard debate between pelvic versus extended-field coverage. Enrolled 1990–1997.
Interventions and follow up
Arm A: Pelvic RT 45 Gy + brachytherapy + concurrent cisplatin 75 mg/m² day 1 + 5-FU 4 g/m² continuous infusion days 1–4, q3wk × 2 cycle
Arm B: Extended-field RT (pelvic + para-aortic, 45 Gy each) + brachytherapy, no chemotherapy
Primary endpoint: Disease-free survival and overall survival
mFollow up: Initial report ~3 years; 8-year update (Eifel JCO 2004)
Arm B: Extended-field RT (pelvic + para-aortic, 45 Gy each) + brachytherapy, no chemotherapy
Primary endpoint: Disease-free survival and overall survival
mFollow up: Initial report ~3 years; 8-year update (Eifel JCO 2004)
Results
5-year DFS: 67% CCRT vs 40% EF-RT, P<.001
5-year OS: 73% CCRT vs 58% EF-RT, P=.004
8-year OS (Eifel 2004): 67% CCRT vs 41% EF-RT
Distant metastases (8-year): 14% CCRT vs 31% EF-RT
5-year OS: 73% CCRT vs 58% EF-RT, P=.004
8-year OS (Eifel 2004): 67% CCRT vs 41% EF-RT
Distant metastases (8-year): 14% CCRT vs 31% EF-RT
Adverse events
Main adverse events: Grade 3–4 hematologic toxicity higher in CCRT arm (19% vs 2%). Grade 4 GI toxicity: 2% CCRT vs 4% EF-RT (not significantly different). Grade 4 GU toxicity: 1% in both arms. No significant increase in late bowel toxicity with CCRT despite initial concern.
Conclusions
Concurrent cisplatin-based chemoradiation to the pelvis is superior to extended-field radiotherapy for locally advanced cervical cancer, improving both DFS and OS substantially. Concurrent chemotherapy also reduced the rate of distant metastases, suggesting a systemic as well as radiosensitizing effect. This trial was among the five concurrent chemoradiation trials for cervical cancer that prompted the 1999 NCI Clinical Announcement.
Key Limitations
Key Limitations: Extended-field RT without chemotherapy as comparator — this is no longer standard practice, so the trial does not address the question of whether CCRT to extended field is superior to CCRT to pelvis alone in node-positive disease. Brachytherapy was delivered with LDR, not modern image-guided HDR. The trial predates IMRT and modern contouring guidelines. Long-term data show durable benefit but no OS plateau, with continued late relapses.
Clinical Context
RTOG 9001 is one of the landmark trials establishing concurrent cisplatin-based chemoradiation as the standard of care for locally advanced cervical cancer. Together with GOG 120 and GOG 109, it catalyzed the 1999 NCI announcement. Modern practice delivers weekly cisplatin 40 mg/m² with pelvic IMRT + MRI-guided adaptive brachytherapy (based on RetroEMBRACE). For node-positive disease, extended-field IMRT is now used concurrently with chemotherapy.
References