Table 2 |.
Trials testing adjuvant radiotherapy in patients with EC
| Trial | Population characteristics and intervention | Recurrence outcomes | OS |
|---|---|---|---|
| GOG-99101 (phase III) |
392 patients with intermediate-riska EC who underwent abdominal staging surgery including total hysterectomy and routine lymphadenectomy were randomized (1:1) to pelvic EBRT (total 50.48 Gy with >28 180-cGy fractions) vs observation | Overall: 2-year CIR 3% vs 12%; HR 0.42, 90% CI 0.25–0.73; P = 0.007 | Overall: estimated 4-year OS 92% vs 86%; HR 0.86, 90% CI 0.57–1.29; P = 0.55 |
| High–intermediate risk: 2-year CIR 26% vs 6%; HR 0.42, 90% CI 0.21–0.83 | High–intermediate risk: estimated 4-year OS 88% vs74%; HR 0.73, 90% CI 0.43–1.26 |
||
| Low–intermediate risk: 2-year CIR 5% vs 2%; HR 0.46, 90% CI 0.19–1.11 | Low–intermediate risk: estimated 4-year OS 94% vs 92% HR 1.04; 90% CI 0.56–1.93 |
||
| PORTEC-1102,104, 115 (phase III) |
715 patients with stage 1 (grade 1–3) EC who underwent total abdominal hysterectomy and bilateral salpingo–oophorectomy, without lymphadenectomy were randomized (1:1) to pelvic EBRT (total of 46 Gy delivered as 2-Gy daily fractions) vs observation | 5-year LRR 4% vs 14%, P <0.001; 5-year LRR in patients with aberrant p53 3.8% vs 27.8%, P = 0.15b, 5-year LRR in patients with NSMP 1.7% vs 12.3%, P = 4.6 × 10−4b; DRR 7.9% vs 7% | 5-year OS 81% vs 85%, P = 0.31 |
| PORTEC-2103,105, 115 (phase III) |
427 patients with stage I–IIA high–intermediate risk EC who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without lymphadenectomy were randomized (1:1) to VBT (21-Gy high-dose rate or 30 Gy low-dose rate) vs pelvic EBRT (46 Gy delivered as 23 fractions) | 5-year LRR 5.1% vs 2.1%, HR 2.08, 95% CI 0.71–6.09, P = 0.17; p53abn 0% vs 31.4%b, P = 0.06, NSMP 1.8% vs 2.3%, P = 0.38b 5-year pelvic recurrence 1.5% vs 0.5%, HR 3.1, 95% CI 0.32–29.9, P = 0.30; 5-year vaginal recurrence 1.8% vs 1.6%, HR 0.78, 95% CI 0.17–3.49, P = 0.74; 5-year distant recurrence 8.3% vs 5.7%, HR 1.32, 95% CI 0.62–2.74, P = 0.46 |
5-year OS 84.8% vs 79.6%, HR 1.17, 95% CI 0.69–1.98, P = 0.57 |
| PORTEC-3 109 (phase III) |
660 patients with stage I–III EC who underwent total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy, with optional lymphadenectomy were randomized (1:1) to CRT (48.6 Gy EBRT delivered in 1.8-Gy fractions plus 2 cycles of cisplatin on week 1 and week 4 of RT followed by 4 cycles of carboplatin–paclitaxel vs pelvic EBRT (48.6 Gy delivered in 1.8-Gy fractions) only | 5-year PFS 76.5% vs 69.1%, HR 0.70, 95% CI 0.52–0.94, P = 0.02; MMRd 68% vs 75.5%, HR 1.29, 95% CI 0.68–2.45, P = 0.43b; p53abn 58.6% vs 36.2%, HR 0.52, 95% CI 0.30–0.91, P = 0.02b; NSMP 79.7% vs 67.7%, HR 0.68, 95% CI 0.36–1.30, P = 0.25b |
5-year OS 81.4% vs 76.1%, HR 0.70, 95% CI 0.51–0.97, P = 0.03; MMRd 78.6% vs 84%, HR 1.33, 95% CI 0.64–2.75, P = 0.45a; p53abn 64.9% vs 41.8%, HR 0.55, 95% CI 0.30–1.0, P = 0.05b; NSMP 89.3% vs 87.6%, HR 0.68, 95% CI 0.26–1.77, P = 0.44b |
| Stage I–II: 5-year PFS 81.3% vs 77.3%; HR 0.87, 95% CI 0.56–1.36; P = 0.54 | Stage I–II: 5-year OS 83.8% vs 82.0%; HR 0.84, 95% CI 0.52–1.38; P = 0.50 | ||
| Stage III: 5-year PFS 70.9% vs 58.4%; HR 0.61, 95% CI 0.42–0.89; P = 0.01 | Stage III: 5-year OS 78.5% vs 68.5%; HR 0.63, 95% CI 0.41–0.99; P = 0.04 | ||
| Serous only: 5-year PFS 59.7% vs 47.9%; HR 0.42, 95% CI 0.22–0.80; P = 0.008 | Serous only: 5-year OS 71.4% vs 52.8%; HR 0.48, 95% CI 0.24–0.96; P = 0.04 | ||
| GOG-258110, 111
(phase III) |
707 patients with surgically staged III–IVA (stage I/II serous or clear cell permitted if positive peritoneal washings) EC who underwent hysterectomy and bilateral salpingo-oophorectomy with optional lymphadenectomy were randomized (1:1) to CRT (45 Gy EBRT delivered in 1.8-Gy fractions plus 2 cycles of cisplatin on days 1 and 29 of RT followed by 4 cycles of carboplatin–paclitaxel vs 6 cycles of carboplatin–paclitaxel | 5-year PFS 59% vs 58%, HR 0.90, 90% CI 0.74–1.10; P = 0.20; 5-year vaginal recurrence 2% vs 7% HR 0.36 (95% CI 0.16–0.82); 5-year nodal recurrence 11% vs 20%, HR 0.43, 95% CI 0.28–0.66; 5-year distant recurrence 27% vs 21%, HR 1.36, 95% CI 1.0–1.86 |
mOS NR vs NR; HR 1.05, 95% CI 0.82–1.34; P = 0.72 |
| GOG-249106 (phase III) |
601 patients with stage I–II high–intermediate risk EC who underwent hysterectomy with bilateral pelvic and para-aortic lymphadenectomy also recommended were randomized (1:1) to EBRT (45–50.4 Gy delivered in 1.8-Gy fractions) vs VBT (high dose-rate or low dose-rate) followed by 3 cycles of carboplatin–paclitaxel | 5-year RFS HR 0.92, 95% CI 0.65 – 1.30; P = 0.31 | 5-year OS HR 1.04, 95% CI 0.66 – 1.63; P = 0.57 |
| Stage I endometrioid: 5-year RFS HR 0.90, 95% CI 0.56–1.45 | Stage I endometrioid: 5-year OS HR 1.12, 95% CI 0.60–2.06 | ||
| Stage II endometrioid: 5-year RFS HR 1.21, 95% CI 0.52–2.79 | Stage II endometrioid: 5-year OS HR 2.04, 95% CI 0.51–8.15 | ||
| Stage I serous/clear cell: 5-year RFS HR 1.17, 95% CI 0.54–2.53 | Stage I serous/clear cell: 5-year OS HR 0.93, 95% CI 0.34–2.57 | ||
| Stage II serous/clear cell: 5-year RFS HR 0.39, 95% CI 0.12–1.28 | Stage II serous/clear cell: 5-year OS HR 0.67, 95% CI 0.19–2.38 |
abn, abnormal; CI, confidence interval; CIR, cumulative incidence of recurrence; DMI, depth of myometrial invasion; DRR, durable response rate; EC, endometrial carcinoma; EBRT, external beam radiation therapy; HR, hazard ratio; LRR, locoregional recurrence rate; LVSI, lymphovascular space invasion; MMRd, mismatch-repair deficient; NR, not reported; NSMP, no specific molecular profile; OS overall survival; PFS, progression-free survival; mut, mutation; RFS, recurrence-free survival; RT, radiotherapy; VBT, vaginal brachytherapy.
a
GOG-99 high–intermediate risk criteria: ≥70 years of age with one uterine risk factor, ≥50 years of age with two uterine risk factors, or <50 years of age with 3 uterine risk factors. Uterine risk factors include grade 2–3 tumours, DMI ≥50%, and lymphovascular invasion.
b
Data are from a post-hoc analysis.