What are the recommendations for using Portec (Portable Medical Device) in clinical practice?

PORTEC Trials: Clinical Implications for Endometrial Cancer Management

Overview of PORTEC Trial Series

The PORTEC (Post Operative Radiation Therapy in Endometrial Carcinoma) trials are landmark randomized controlled trials that have fundamentally shaped adjuvant treatment decisions for endometrial cancer, demonstrating that vaginal brachytherapy alone is sufficient for high-intermediate risk disease, while combined chemoradiotherapy provides survival benefit specifically for high-risk patients with stage III or serous histology. 1, 2

Key Trial Findings and Treatment Recommendations

PORTEC-2: High-Intermediate Risk Endometrial Cancer

• Vaginal brachytherapy (VBT) is the standard adjuvant treatment for high-intermediate risk endometrial cancer, with 10-year vaginal recurrence rates of only 3.4% versus 2.4% for VBT versus external beam radiotherapy (EBRT), showing no significant difference (p=0.55) 3

• Pelvic recurrence was higher with VBT (6.3% vs 0.9%, p=0.004), but most occurred with concurrent distant metastases, and isolated pelvic recurrence remained low at 2.5% versus 0.5% (p=0.10) 3

• Overall survival at 10 years was equivalent between VBT and EBRT (69.5% vs 67.6%, p=0.72), confirming VBT as the preferred approach due to lower toxicity with similar survival outcomes 3

• EBRT should be considered for patients with unfavorable molecular markers including L1CAM expression, p53-mutant expression, or substantial lymph-vascular space invasion, as these factors predict pelvic and distant recurrence 3

PORTEC-3: High-Risk Endometrial Cancer

• Combined adjuvant chemoradiotherapy (cisplatin during radiation followed by carboplatin/paclitaxel) significantly improves both overall survival and failure-free survival compared to radiotherapy alone in high-risk endometrial cancer 2

• At 5-year follow-up, overall survival was 81.4% with chemoradiotherapy versus 76.1% with radiotherapy alone (HR 0.70,95% CI 0.51-0.97, p=0.034) 2

• Failure-free survival at 5 years was 76.5% with chemoradiotherapy versus 69.1% with radiotherapy alone (HR 0.70,95% CI 0.52-0.94, p=0.016) 2

• The primary benefit of chemotherapy is reduction in distant metastases (21.4% vs 29.1% at 5 years, HR 0.74, p=0.047), while isolated vaginal and pelvic recurrences remained similarly low in both groups 2

Molecular Classification Impact (PORTEC-3 Molecular Analysis)

Molecular classification fundamentally changes treatment selection and provides the strongest prognostic information beyond traditional clinicopathologic factors 4

Four Molecular Subgroups with Distinct Outcomes:

• p53-abnormal tumors (23% of high-risk EC): Worst prognosis with 5-year RFS of only 48%, but showed dramatic benefit from chemoradiotherapy (59% vs 36% RFS, p=0.019) 4

• POLE-ultramutated tumors (12%): Excellent prognosis with 98% 5-year RFS, no benefit from chemotherapy (100% vs 97%, p=0.637), suggesting these patients can avoid chemotherapy toxicity 4

• MMR-deficient tumors (33%): Intermediate prognosis with 72% 5-year RFS, no clear benefit from chemotherapy (68% vs 76%, p=0.428) 4

• No specific molecular profile (32%): Intermediate prognosis with 74% 5-year RFS, trend toward benefit from chemotherapy not reaching significance (80% vs 68%, p=0.243) 4

Treatment Algorithm Based on PORTEC Evidence

For High-Intermediate Risk EC (Stage IA Grade 3 or Stage IB Grade 1-2):

• Recommend vaginal brachytherapy alone as standard treatment 3
• Consider EBRT only if molecular markers show L1CAM expression, p53-mutant expression, or substantial LVSI 3

For High-Risk EC (Stage I-III with deep invasion, LVSI, or serous/clear cell histology):

• Obtain molecular classification (p53 IHC, MMR IHC, POLE sequencing) before finalizing adjuvant treatment plan 4
• p53-abnormal tumors: Strongly recommend combined chemoradiotherapy (cisplatin concurrent with RT, followed by carboplatin/paclitaxel) 2, 4
• POLE-ultramutated tumors: Radiotherapy alone is sufficient; avoid chemotherapy toxicity 4
• MMR-deficient and NSMP tumors: Discuss chemoradiotherapy versus radiotherapy alone, with stronger consideration for stage III disease 2, 4

Toxicity Considerations

• Acute toxicity with chemoradiotherapy is substantial: 61% experienced grade 3+ adverse events during treatment (mostly hematologic at 45%) versus 13% with radiotherapy alone 1

• Sensory neuropathy is the primary persistent toxicity: At 24 months, 25% of chemoradiotherapy patients reported severe tingling/numbness versus 6% with radiotherapy alone (p<0.0001) 1

• Grade 2+ sensory neuropathy persisted at 5 years in 6% of chemoradiotherapy patients versus 0% with radiotherapy alone 2

• Recovery of quality of life occurs by 12 months after chemoradiotherapy, with global health scores similar between groups, though physical functioning remains slightly lower 1

Predictive Nomograms for Decision Support

• Validated nomograms from pooled PORTEC-1 and PORTEC-2 data (N=1240 patients) accurately predict locoregional relapse, distant relapse, overall survival, and disease-free survival with c-indices of 0.69-0.78 5

• Most predictive factors across all outcomes: age, tumor grade, and lymph-vascular space invasion 5

• These nomograms can quantify individual patient risk to guide shared decision-making regarding adjuvant treatment intensity 5

Critical Clinical Pitfalls to Avoid

• Do not use EBRT for high-intermediate risk disease without molecular risk stratification, as VBT provides equivalent survival with lower toxicity 3

• Do not withhold chemoradiotherapy from patients with p53-abnormal tumors regardless of stage, as this subgroup derives the greatest survival benefit 4

• Do not routinely give chemotherapy to patients with POLE-ultramutated tumors, as their excellent prognosis makes the toxicity unjustifiable 4

• Do not make treatment decisions based solely on histologic type (serous vs endometrioid); molecular classification provides superior prognostic and predictive information 4