PORTEC-3 Treatment Protocol for High-Risk Endometrial Cancer
Yes, your understanding is essentially correct: PORTEC-3 established combined chemoradiotherapy followed by adjuvant chemotherapy as the standard approach for stage III endometrial cancer, serous histology, and p53-abnormal tumors, demonstrating improved failure-free survival compared to radiotherapy alone. 1
Specific Patient Populations in PORTEC-3
The PORTEC-3 trial enrolled patients with the following high-risk features: 1
- Stage I grade 3 endometrioid with deep myometrial invasion or lymphovascular space invasion 1
- Stage II-III endometrioid disease of any grade 1
- Stage I-III serous or clear cell histology 2
Standard Treatment Regimen
The established protocol consists of concurrent chemoradiotherapy followed by sequential chemotherapy: 3, 4
- Concurrent phase: External beam radiotherapy 48.6 Gy (1.8 Gy fractions, 5 days/week) with cisplatin 50 mg/m² on days 1 and 29 3, 4
- Sequential phase: Four cycles of carboplatin AUC5 plus paclitaxel 175 mg/m² every 3 weeks 3, 4, 1
Survival Outcomes
The PORTEC-3 trial demonstrated: 1
- 5-year overall survival: 81.8% with chemoradiotherapy versus 76.7% with radiotherapy alone (HR 0.76, p=0.11) 1
- 5-year failure-free survival: 75.5% with chemoradiotherapy versus 68.6% with radiotherapy alone (HR 0.71, p=0.022) 1
While overall survival improvement did not reach statistical significance at 5 years, the National Comprehensive Cancer Network guidelines now recommend chemoradiotherapy based on updated analysis showing significant overall survival benefit (HR 0.70,95% CI 0.51-0.97, p=0.034). 3
Greatest Benefit Populations
Patients with stage III disease and serous histology derive the most substantial survival benefit from combined chemoradiotherapy. 3, 4
Molecular Classification Impact
P53-abnormal tumors show a 23% absolute recurrence-free survival improvement with chemotherapy, making combined modality treatment particularly important for this molecular subtype. 3
- P53-abnormal tumors should receive chemotherapy regardless of stage 3
- POLE-ultramutated tumors show excellent prognosis without chemotherapy and may not require it 3
- Molecular classification should guide treatment intensity decisions 3, 5
Toxicity Profile
Grade 3 or worse adverse events occurred in 60% of chemoradiotherapy patients versus 12% with radiotherapy alone (p<0.0001), with most being hematological (45%). 1
- Persistent sensory neuropathy (grade 2 or worse) occurs in 8% at 3 years versus 1% with radiotherapy alone 1
- Long-term neuropathy persists in 6% of patients at 5 years 3
Alternative Approach: Chemotherapy Alone
The GOG-258 trial demonstrated equivalent recurrence-free survival between chemotherapy alone (6 cycles carboplatin/paclitaxel) versus chemoradiotherapy (HR 0.9,95% CI 0.74-1.10). 4
Critical Caveat
Chemotherapy alone resulted in significantly higher locoregional recurrence rates: 4
- Vaginal recurrence: 7% versus 3% with chemoradiotherapy 4
- Pelvic/para-aortic recurrence: 21% versus 10% with chemoradiotherapy 4
- Distant recurrences paradoxically higher with chemoradiotherapy: 28% versus 21% 4
Therefore, chemotherapy alone is not adequate for high-risk endometrial cancer when locoregional control is a priority. 3
Stage-Specific Recommendations
Stage III Disease
Combined chemoradiotherapy is the standard of care for stage III endometrial cancer, providing both systemic and locoregional control. 3, 4
- Maximal surgical cytoreduction should precede adjuvant therapy 4
- The Society of Gynecologic Oncology reports 78.7% 5-year overall survival with combined treatment 4
Serous Histology (Any Stage)
Serous carcinomas require aggressive treatment regardless of stage due to their inherently aggressive biology. 2