PORTEC-2
Needs reviewVaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2)
Phase 3N = 427NCT00376844
- Population
- Stage I or IIA endometrial carcinoma with features of high-intermediate risk, after surgery
- Design
- Open-label, non-inferiority, randomised trial in 19 Dutch radiation oncology centres: 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were randomised to pelvic EBRT (46 Gy in 23 fractions) or vaginal brachytherapy (21 Gy high-dose rate in three fractions, or 30 Gy low-dose rate), 2002 to 2006. Primary endpoint vaginal recurrence; predefined non-inferiority margin an absolute difference of 6% in vaginal recurrence. Analysis by intention to treat with competing-risk methods. Median follow-up 45 months at the primary report and 116 months at the 10-year report.
- Primary endpoint
- Vaginal recurrence
- Arms
- Pelvic external beam radiotherapy (control, n = 214): Pelvic EBRT, 46 Gy in 23 fractions
- Vaginal brachytherapy (experimental, n = 213): Vaginal brachytherapy, 21 Gy high-dose rate in three fractions, or 30 Gy low-dose rate
- People
- Nout RA
Vaginal recurrenceHR 0.78 (95% CI 0.17–3.49)Δ 60-month Vaginal recurrence+0.2 pointsLocoregional recurrenceHR 2.08 (95% CI 0.71–6.09)Δ 60-month Locoregional recurrence+3 pointsDistant metastasisHR 1.32 (95% CI 0.63–2.74)Δ Distant metastasis+2.6 points
Show the numbers
| Endpoint | Analysis | Vaginal brachytherapy | Pelvic external beam radiotherapy | Effect |
|---|---|---|---|---|
| Vaginal recurrenceEstimated 5-year cumulative incidence of vaginal recurrence (competing-risk methods); predefined non-inferiority margin an absolute difference of 6% | primarymedian follow-up 45 monthsNout 2010 | 1.8% at 5 y (0.6–5.9%) | 1.6% at 5 y (0.5–4.9%) | HR 0.78 (95% CI 0.17–3.49)P=0.74Three vaginal recurrences were diagnosed after vaginal brachytherapy and four after pelvic EBRT (range of follow-up 18 to 78 months). The abstract does not state which arm is the reference for the hazard ratio. |
| Locoregional recurrencePublished as locoregional relapse: vaginal or pelvic recurrence, or both; estimated 5-year rate | primarymedian follow-up 45 monthsNout 2010 | 5.1% at 5 y (2.8–9.6%) | 2.1% at 5 y (0.8–5.8%) | HR 2.08 (95% CI 0.71–6.09)P=0.17 |
| Distant metastasisRate of distant metastases; the abstract sentence does not restate the time point | primarymedian follow-up 45 monthsNout 2010 | 8.3% (5.1–13.4%) | 5.7% (3.3–9.9%) | HR 1.32 (95% CI 0.63–2.74)P=0.46The abstract describes the rates of distant metastases as similar. It does not state the time point or the reference arm of the hazard ratio. |
| OSOverall survival; the abstract sentence does not restate the time point | primarymedian follow-up 45 monthsNout 2010 | 84.8% (79.3–90.3%) | 79.6% (71.2–88.0%) | HR 1.17 (95% CI 0.69–1.98)P=0.57The abstract reports no difference in overall survival. It does not state the time point of the percentages or the reference arm of the hazard ratio. |
| DFSDisease-free survival; the abstract sentence does not restate the time point | primarymedian follow-up 45 monthsNout 2010 | 82.7% (76.9–88.6%) | 78.1% (69.7–86.5%) | HR 1.09 (95% CI 0.66–1.78)P=0.74The abstract reports no difference in disease-free survival. It does not state the time point of the percentages or the reference arm of the hazard ratio. |
| Acute grade 1-2 gastrointestinal toxicityPatients assessed at completion of radiotherapy (27 of 215 vaginal brachytherapy, 112 of 208 pelvic EBRT)Acute grade 1-2 gastrointestinal toxicity at completion of radiotherapy | primaryNout 2010 | 12.6% | 53.8% | The abstract describes the rate as significantly lower with vaginal brachytherapy and gives no p-value. |
| Vaginal recurrenceAll 427 randomised women10-year vaginal recurrence | long term-updatemedian follow-up 116 monthsWortman 2018 | 3.4% at 10 y | 2.4% at 10 y | P=0.55 |
| Pelvic recurrenceAll 427 randomised women10-year pelvic recurrence; mostly combined with distant metastases. Isolated pelvic recurrence was 2.5% vs 0.5% (p=0.10) and distant metastases 10.4% vs 8.9% (p=0.45) | long term-updatemedian follow-up 116 monthsWortman 2018 | 6.3% at 10 y | 0.9% at 10 y | P=0.004 |
| OSAll 427 randomised women10-year overall survival | long term-updatemedian follow-up 116 monthsWortman 2018 | 69.5% at 10 y | 67.6% at 10 y | P=0.72 |
| Endpoint | Analysis | Vaginal brachytherapy | Pelvic external beam radiotherapy | Effect |
|---|---|---|---|---|
| Vaginal recurrenceEstimated 5-year cumulative incidence of vaginal recurrence (competing-risk methods); predefined non-inferiority margin an absolute difference of 6% | primarymedian follow-up 45 monthsNout 2010 | 1.8% at 5 y (0.6–5.9%) | 1.6% at 5 y (0.5–4.9%) | HR 0.78 (95% CI 0.17–3.49)P=0.74Three vaginal recurrences were diagnosed after vaginal brachytherapy and four after pelvic EBRT (range of follow-up 18 to 78 months). The abstract does not state which arm is the reference for the hazard ratio. |
| Locoregional recurrencePublished as locoregional relapse: vaginal or pelvic recurrence, or both; estimated 5-year rate | primarymedian follow-up 45 monthsNout 2010 | 5.1% at 5 y (2.8–9.6%) | 2.1% at 5 y (0.8–5.8%) | HR 2.08 (95% CI 0.71–6.09)P=0.17 |
| Distant metastasisRate of distant metastases; the abstract sentence does not restate the time point | primarymedian follow-up 45 monthsNout 2010 | 8.3% (5.1–13.4%) | 5.7% (3.3–9.9%) | HR 1.32 (95% CI 0.63–2.74)P=0.46The abstract describes the rates of distant metastases as similar. It does not state the time point or the reference arm of the hazard ratio. |
| OSOverall survival; the abstract sentence does not restate the time point | primarymedian follow-up 45 monthsNout 2010 | 84.8% (79.3–90.3%) | 79.6% (71.2–88.0%) | HR 1.17 (95% CI 0.69–1.98)P=0.57The abstract reports no difference in overall survival. It does not state the time point of the percentages or the reference arm of the hazard ratio. |
| DFSDisease-free survival; the abstract sentence does not restate the time point | primarymedian follow-up 45 monthsNout 2010 | 82.7% (76.9–88.6%) | 78.1% (69.7–86.5%) | HR 1.09 (95% CI 0.66–1.78)P=0.74The abstract reports no difference in disease-free survival. It does not state the time point of the percentages or the reference arm of the hazard ratio. |
| Acute grade 1-2 gastrointestinal toxicityPatients assessed at completion of radiotherapy (27 of 215 vaginal brachytherapy, 112 of 208 pelvic EBRT)Acute grade 1-2 gastrointestinal toxicity at completion of radiotherapy | primaryNout 2010 | 12.6% | 53.8% | The abstract describes the rate as significantly lower with vaginal brachytherapy and gives no p-value. |
| Vaginal recurrenceAll 427 randomised women10-year vaginal recurrence | long term-updatemedian follow-up 116 monthsWortman 2018 | 3.4% at 10 y | 2.4% at 10 y | P=0.55 |
| Pelvic recurrenceAll 427 randomised women10-year pelvic recurrence; mostly combined with distant metastases. Isolated pelvic recurrence was 2.5% vs 0.5% (p=0.10) and distant metastases 10.4% vs 8.9% (p=0.45) | long term-updatemedian follow-up 116 monthsWortman 2018 | 6.3% at 10 y | 0.9% at 10 y | P=0.004 |
| OSAll 427 randomised women10-year overall survival | long term-updatemedian follow-up 116 monthsWortman 2018 | 69.5% at 10 y | 67.6% at 10 y | P=0.72 |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| Vaginal recurrence | 0.78 | 0.17–3.49 |
| Locoregional recurrence | 2.08 | 0.71–6.09 |
| Distant metastasis | 1.32 | 0.63–2.74 |
| OS | 1.17 | 0.69–1.98 |
| DFS | 1.09 | 0.66–1.78 |
Appears in
Sources
Nout RA, Smit VT, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, et al. 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. Lancet. 2010;375(9717):816-23.
Wortman BG, Creutzberg CL, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LCHW, et al. Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy. Br J Cancer. 2018;119(9):1067-1074.