What are the recommendations for a patient enrolled in the Portec 3 (Portec 3 trial) medical study?

PORTEC-3 Trial: Recommendations for High-Risk Endometrial Cancer

For patients with high-risk endometrial cancer meeting PORTEC-3 eligibility criteria, combined chemoradiotherapy (radiotherapy with concurrent and adjuvant chemotherapy) should be recommended over radiotherapy alone, particularly for those with stage III disease or serous histology, as this approach significantly improves both overall survival and failure-free survival. 1, 2, 3

Patient Eligibility Criteria

Patients appropriate for PORTEC-3 enrollment or PORTEC-3-based treatment include those with: 1, 2

• Stage I, grade 3 endometrioid cancer with deep myometrial invasion AND/OR lymphovascular space invasion (LVSI) 1, 2
• Stage II or III disease (any grade) 1, 2
• Stage I-III with serous or clear cell histology 1, 2
• Age ≥18 years with WHO performance status 0-2 3

Critical caveat: Central pathology review by expert gynecologic pathologists is essential before treatment initiation, as discrepancies occur in 43% of cases and lead to ineligibility in 8% of patients, most commonly due to misclassification of histological type (34%), endocervical stromal involvement (27%), or histological grade (19%). 4

Treatment Protocol

Chemoradiotherapy Regimen (Preferred for High-Risk Disease)

Radiotherapy component: 1, 2

• External beam pelvic radiotherapy: 48.6 Gy in 1.8 Gy fractions, 5 days per week

Concurrent chemotherapy: 1, 2

• Cisplatin 50 mg/m² IV during weeks 1 and 4 of radiotherapy (2 cycles total)

Adjuvant chemotherapy: 1, 2

• Carboplatin AUC5 + Paclitaxel 175 mg/m² IV for 4 cycles following radiotherapy completion

Efficacy Outcomes

At median follow-up of 72.6 months: 3

• 5-year overall survival: 81.4% with chemoradiotherapy vs 76.1% with radiotherapy alone (HR 0.70,95% CI 0.51-0.97, p=0.034)
• 5-year failure-free survival: 76.5% with chemoradiotherapy vs 69.1% with radiotherapy alone (HR 0.70,95% CI 0.52-0.94, p=0.016)
• Distant metastases reduction: 21.4% with chemoradiotherapy vs 29.1% with radiotherapy alone (HR 0.74,95% CI 0.55-0.99, p=0.047) 3

Greatest benefit observed in: 1

• Stage III disease
• Serous histology
• Both stage III AND serous histology combined

Toxicity Profile and Patient Counseling

Acute Toxicity (During Treatment)

Grade 3 or worse adverse events: 2, 5

• Chemoradiotherapy: 61% of patients (predominantly hematological toxicity at 45%)
• Radiotherapy alone: 13% of patients
• Most common grade 3 events: hematological complications 5

Long-Term Toxicity (24+ Months)

Persistent sensory neuropathy (grade 2 or worse): 5, 3

• At 24 months: 10% with chemoradiotherapy vs <1% with radiotherapy alone (p<0.0001)
• At 5 years: 6% with chemoradiotherapy vs 0% with radiotherapy alone 3
• Patient-reported severe tingling/numbness at 24 months: 25% with chemoradiotherapy vs 6% with radiotherapy alone (p<0.0001) 5

Grade 3 or worse late adverse events at 5 years: 3

• Chemoradiotherapy: 8% of patients
• Radiotherapy alone: 5% of patients (p=0.24, not statistically significant)
• Most common: hypertension (2% in both groups) 3

Quality of Life Recovery

Functional recovery timeline: 5

• Functioning scales significantly worse at radiotherapy completion and 6 months post-treatment
• Recovery to baseline by 12-24 months for most domains
• Physical functioning remains slightly lower in chemoradiotherapy group at 24 months
• Global health/quality of life equivalent between groups at 12 and 24 months 5

Clinical Decision Algorithm

For Stage III or Serous Histology: Strongly recommend chemoradiotherapy as these subgroups derive the greatest survival benefit. 1, 3

For Stage I Grade 3 with Deep Invasion: Recommend chemoradiotherapy with detailed discussion of the 5% absolute overall survival benefit at 5 years versus persistent neuropathy risk (6% at 5 years). 2, 3

For Stage II Disease: Recommend chemoradiotherapy, emphasizing the significant reduction in distant metastases (8% absolute reduction). 3

Patient factors favoring radiotherapy alone: 5

• Pre-existing neuropathy
• Significant comorbidities precluding chemotherapy tolerance
• Patient preference after informed discussion of survival benefit versus toxicity trade-offs

Common Pitfalls to Avoid

Do not proceed without central pathology review by expert gynecologic pathologists, as local pathology misclassifies histological type, grade, or other critical features in 43% of cases. 4

Do not assume PORTEC-1 or PORTEC-2 data apply to stage IC grade 3 disease, as these trials specifically excluded this highest-risk subset. 6

Do not use vaginal brachytherapy alone for PORTEC-3-eligible patients, as this approach was not evaluated in high-risk disease and PORTEC-2 specifically excluded stage IC grade 3 patients. 6

Do not delay treatment initiation for molecular profiling outside of clinical trials, though ongoing PORTEC-4a may refine future recommendations based on molecular classification. 1

Molecular Considerations

Recent molecular analysis identified four prognostic subgroups (p53 abnormal, POLE-ultramutated, MMR-deficient, no specific molecular profile), but treatment decisions should currently be based on clinicopathologic features pending completion of PORTEC-4a trial results. 1