What are the recommendations for participating in the Portec (Portec trials) clinical trials?

PORTEC Trials Recommendations

Participation in PORTEC trials should be considered for patients with high-risk endometrial cancer, particularly those with stage III disease or serous histology, as these patients show the greatest survival benefit from combined chemoradiotherapy versus radiotherapy alone. 1, 2

Overview of PORTEC Trials

The PORTEC (Post Operative Radiation Therapy in Endometrial Carcinoma) trials are a series of landmark studies that have shaped the management of endometrial cancer:

• PORTEC-1: Evaluated external beam radiation therapy (EBRT) versus observation in intermediate-risk endometrial cancer, showing improved locoregional control but no overall survival benefit 1
• PORTEC-2: Compared EBRT versus vaginal brachytherapy in high-intermediate risk patients, demonstrating equivalent vaginal and pelvic control with less toxicity with brachytherapy 1
• PORTEC-3: Investigated combined chemoradiotherapy versus radiotherapy alone in high-risk endometrial cancer, showing improved failure-free survival and overall survival with combined therapy 1, 3
• PORTEC-4a: Ongoing trial investigating molecular profile-based directed adjuvant treatment in high-risk endometrial cancer 1

Patient Selection Criteria

PORTEC-3 Eligibility (Most Recent Trial)

Patients with the following characteristics may be considered for participation in PORTEC-3 or similar trials:

• Stage I, grade 3 with deep myometrial invasion, lymphovascular space invasion (LVSI), or both 1, 3
• Stage II or III disease 1, 3
• Stage I-III with serous or clear cell histology 1, 3
• WHO performance status of 0-2 3
• Age 18 years or older 3

High-Intermediate Risk Definition (PORTEC-1 and PORTEC-2)

For PORTEC-1 and PORTEC-2 trials, high-intermediate risk was defined as having 2 of 3 risk factors:

• Age >60 years
• Deep myometrial invasion (≥50%)
• Grade 3 histology 1

Treatment Approaches Based on PORTEC Trials

For High-Risk Endometrial Cancer (PORTEC-3)

• Combined chemoradiotherapy: EBRT (48.6 Gy in 1.8 Gy fractions) with concurrent cisplatin (50 mg/m²) followed by 4 cycles of carboplatin/paclitaxel 3, 2
• 5-year overall survival: 81.4% with chemoradiotherapy vs. 76.1% with radiotherapy alone 2
• Greatest benefit observed in patients with stage III disease and serous histology 1, 2

For High-Intermediate Risk Endometrial Cancer (PORTEC-2)

• Vaginal brachytherapy alone is the standard recommendation due to equivalent local control and reduced toxicity compared to EBRT 1, 4
• 10-year vaginal recurrence rates: 3.4% for vaginal brachytherapy vs. 2.4% for EBRT (not statistically significant) 4

Molecular Classification Impact (PORTEC-3)

Recent molecular analysis of PORTEC-3 samples has identified four molecular subgroups with significant prognostic implications:

• p53 abnormal: Greatest benefit from chemoradiotherapy (5-year RFS: 59% with chemoradiotherapy vs. 36% with radiotherapy alone) 1, 5
• POLE-ultramutated: Excellent prognosis regardless of treatment (5-year RFS: 100% with chemoradiotherapy vs. 97% with radiotherapy alone) 1, 5
• MMR-deficient: No significant difference between treatments 1, 5
• No specific molecular profile: No significant difference between treatments 1, 5

Toxicity and Quality of Life Considerations

Patients considering participation should be aware of potential toxicities:

• Grade 3 or worse adverse events during treatment: 60% with chemoradiotherapy vs. 12% with radiotherapy alone 3
• Persistent sensory neuropathy (grade 2 or worse) at 24 months: 25% with chemoradiotherapy vs. <1% with radiotherapy alone 6
• Despite increased toxicity, rapid recovery occurs after treatment completion, with similar global health/quality of life scores by 12 months 6

Common Pitfalls and Caveats

• PORTEC-1 and PORTEC-2 specifically excluded patients with 1998 FIGO stage 1C and grade 3 endometrial carcinoma (2009 FIGO stage IB, grade 3), so recommendations for this higher-risk subset remain controversial 1
• PORTEC studies did not evaluate lymph nodes; therefore, in the context of complete surgical staging, the need for pelvic irradiation remains controversial in uterine-confined disease 1
• The ongoing PORTEC-4a trial may further refine treatment recommendations based on molecular profiling 1
• Molecular classification should be incorporated into risk stratification when considering trial participation, as it significantly impacts prognosis and treatment benefit 5