PORTEC 2

Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial

Pubmed


Hypothesis: Vaginal brachytherapy is equally effective in prevention of vaginal cuff recurrence of endometrial cancer compared to EBRT in high intermediate risk patients.

Standard Arm: EBRT (46 Gy in 2 Gy fractions)

Experimental Arm: Vaginal brachytherapy (21 Gy in 7 Gy fractions spaced 1 week apart for HDR; 30 Gy at 50–70 cGy/h for the low dose rate; and 28 Gy at 100 cGy/h in one session for the medium-dose rate)

Design: Multicenter RCT in 19 Dutch Radiation Hospitals

Inclusion Criteria: Endometrial adenocarcinoma s/p surgery (no routine lymphadenectomy) with:

  • Age > 60 and stage IC grade ½ or IB grade 3
  • Any age, stage IIA
  • (FIGO 1988 staging)

Exclusion Criteria (outside of usual):

  • Serous or clear cell histology
  • Staging lymphadenectomy
  • Interval between surgery and RT >8 weeks
  • History of prior malignancy
  • Previous RT, hormonal therapy or chemotherapy
  • Crohn’s or UC

Primary Endpoint: Vaginal recurrence

Outcomes: 

  • EBRT: 4 vaginal recurrences (1.6%)
  • Vag Brachy: 3 vaginal recurrences (1.8%)
  • Higher rate of pelvic recurrence in Vag Brachy group (0.5% vs 3.8%, HR 8.29, p=0.02)
  • No overall survival difference (82% vs 86%; NS)


Serious Adverse Events: 

  • EBRT: Grade ½ GI toxicities 53.8%
  • VBT: Grade ½ GI toxicities 12.6% (not significant at 2 years follow up); 

Conclusion: Vaginal brachytherapy provides adequate local control to reduce risk of vaginal recurrence in high-intermediate risk endometrial cancer. It has a favorable side effect profile, with no overall survival benefit.

PORTEC 3

Pubmed

Study Summary by: Dr. Kevin McCool

Title: Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomized, phase 3 trial

Hypothesis: To investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer.

Standard Arm: EBRT (48.6 Gy in 1.8 Gy fractions)

Experimental Arm: EBRT (48.6 Gy) Chemotherapy (Cisplatin 50 mg/m2 in weeks 1 and 4 during RT followed by 4 cycles of Carboplatin AUC5 and Paclitaxel 175 mg/m2)

Design: Open-label, randomized, multi-center (UK, Australia, Italy, Canada, France)Inclusion Criteria:
– Endometrioid:

  • Stage IA Grade 3 with with LVSI

  • Stage IB Grade 3

  • Any Stage II or  III.

  • Serous or Clear Cell: Stage IA (with invasion), IB, II, III

Exclusion Criteria (outside of usual): Carcinosarcoma, prior malignancy within 10 years, prior radiotherapy, hormonal therapy, chemotherapy, bulky cervical involvement with radical hysterectomy, residual macroscopic disease

Primary Endpoint: Co-primary endpoints were failure-free survival (FFS) and overall survival (OS)

Outcomes: ChemoRT vs. RT alone (HR and p-value)

  • OS: 81.8% vs.76.6% [HR 0.76 (p=0.109)]
  • FFS: 75.5% vs. 68.6%[HR 0.71 (p=0.022) favoring chemotherapy RT]
  • Subgroup analysis: Stage III patients
    • 5 year FFS = 69.3% vs 58.0% (HR=0.66, p=0.031)
    • 5 year OS = 78.7% vs. 69.8% (HR=0.71, p=0.13)

Serious Adverse Events: ChemoRT vs. RT alone (p-value)

  • Any hematologic: 45% vs. 5% (p<0.0001)
  • GI: 14% vs. 5% (p<0.0001)
  • Neuropathy: 7% vs. 0% (p<0.0001)
  • At 12 months no significant difference in any grade 3 toxicity

Conclusions:

  • Improvement in FFS with the addition of chemotherapy. OS unchanged
  • Significant improvement in FFS
  • Most benefit in patients with stage III
  • Age is a significant predictor on risk adjustment. Patients above 70 benefit from chemoradiation (however toxicity discussion is warranted)