Critical Analysis of Stage IV Epithelial Ovarian Cancer Patients after Treatment with Neoadjuvant Chemotherapy followed by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC)
Table 4
Published randomized controlled trials assessing the benefit of NACT and/or HIPEC versus debulking surgery in advanced ovarian cancer.
Author and study type
Population and Intervention (no. of CT cycles)
Staging
CT regimen
Study purpose
End points
Tumor burden
Quality of cytoreduction
Median PFS (mos)
Median OS (mos)
Vergote et al. (2010) RCT: EORTC 55971
N = 632 PDS/ACT (6) = 310 vs. NACT (3)/IDS/ACT (3) = 322
PDS vs. NACT IIIC = 77% vs. 76% IV = 23% vs. 24%
Platinum based
Demonstrate noninferiority of NACT compared to PDS
1°: OS 2°: adverse effects, QoL, PFS
Largest preoperative tumor size, PDS vs. NACT: ≤2 cm: 6% vs. 15% ≤5 cm: 16% vs. 23% ≤10 cm: 13% vs. 13% >10 cm: 62% vs. 24% Missing data: 4% vs. 12%
PDS vs. NACT Complete: 19% vs. 51% ≤1 cm: 22% vs. 30% >1–2 cm: 12% vs. 6% >2 cm: 41% vs. 12% missing: 5% vs. 2%
12 (PDS) vs. 12 (NACT)
29 (PDS) vs. 30 (NACT)
Kehoe et al. (2015) RCT: CHORUS
N = 550 PDS/ACT (6) = 276 vs. NACT (3)/IDS/ACT (3) = 274
PDS vs. NACT IIA-IIIB: 11% vs. 12% IIIC = 72% vs. 71% IV = 17% vs. 15%
Platinum and taxane based
Demonstrate noninferiority of NACT compared to PDS
1°: OS 2°: PFS, QoL
Largest preoperative tumor size, PDS vs. NACT: ≤2 cm: 5% vs. 5% ≤5 cm: 21% vs. 22% ≤10 cm: 40% vs. 40% >10 cm: 32% vs. 32% Unmeasurable: 3% vs. 2%
PDS vs. NACT Complete: 17% vs. 39% ≤1 cm: 24% vs. 34% >1 cm: 59% vs. 27%
10.7 (PDS) vs. 12 (NACT)
22.6 (PDS) vs. 24.1 (NACT)
Fagotti et al. (2016) RCT: SCORPION
N = 110 PDS/ACT (6) = 55 vs. NACT (3)/IDS/ACT (3) = 55
PDS vs. NACT IIIC = 86% vs. 93% IV = 14% vs. 7%
Platinum and taxane based ± bevacizumab
Demonstrate superiority of NACT compared to PDS
1°: postoperative complications, PFS 2°: OS, QoL
All with high tumor load (PI score = 8–12) Largest tumor size not reported
PDS vs. NACT Complete: 46% vs. 58% ≤1 cm: 46% vs. 33% >1 cm: 9% vs. 10%
15 (PDS) vs. 14 (NACT)
41 (PDS) vs. NR (NACT)
Onda et al. (2016/2020) RCT: JCOG0602
N = 301 PDS/ACT (8) = 149 vs. NACT (4)/IDS/ACT (4) = 152
PDS vs. NACT III = 67% vs. 69% IV = 33% vs. 31%
Platinum and taxane based
Demonstrate noninferiority and reduced treatment invasiveness in NACT compared to PDS
1°: treatment invasiveness 2°: OS, safety
Tumor burden not reported
PDS vs. NACT Complete: 12% vs. 64% <1 cm: 26% vs. 18% ≥1 cm: 63% vs. 18%
15.1 (PDS) vs. 16.4 (NACT)
49 (PDS) vs. 44.3 (NACT)
Spiliotis et al. (2014) RCT: HIPEC in recurrent EOC
N = 120 CRS/ACT (5) = 60 Vs. CRS-HIPEC/ACT (5) = 60
Non-HIPEC vs. HIPEC III = 58% vs. 68% IV = 42% vs. 32%
HIPEC: Platinum-sensitive = cisplatin and paclitaxel Platinum-resistant = doxorubicin and paclitaxel/mitomycin
Identify the role of HIPEC
Not clearly defined
PCI, HIPEC vs. non-HIPEC: <5: 13% vs. 12% 5–9: 37% vs. 40% ≥10: 50% vs. 48%
CC-score, HIPEC vs. non-HIPEC: CC-0: 55% vs. 65% CC-1: 33% vs. 20% CC-2: 12% vs. 15%
Not reported
13.4 (non-HIPEC) vs. 26.7 (HIPEC)
Van driel et al. (2018) RCT: HIPEC in primary EOC
N = 245 NACT (3)/IDS/ACT (3) = 123 vs. NACT (3)/IDS-HIPEC/ACT (3) = 122
All stage III
Platinum and taxane based
Assess the efficacy and safety of IDS with and without HIPEC
1°: PFS 2°: OS, adverse effects, QoL
Number of regions involved with disease, non-HIPEC vs. HIPEC: 0–5: 67% vs. 68% 6–8: 33% vs. 32%
Non-HIPEC vs. HIPEC Complete: 67% vs. 69% ≤0.25 cm: 20% vs. 18% >0.25–1 cm: 11% vs. 11% >1 cm: 1% vs. 0% None: 2% vs. 3%
10.7 (non-HIPEC) vs. 14.2 (HIPEC)
33.9 (non-HIPEC) vs. 45.7 (HIPEC)
ACT: adjuvant chemotherapy, CT: chemotherapy, EOC: eithelial ovarian cancer, IDS: interval debulking surgery, mos: months, NA: not applicable, NACT: neoadjuvant chemotherapy, OS: overall survival, PDS: primary debulking surgery, PFS: progression-free survival, PI: predictive index, QoL: quality of life, RCT: randomized controlled trial. EOC includes epithelial ovarian carcinoma, fallopian tube carcinoma, or primary peritoneal carcinoma. Laparoscopic predictive index as defined by Fagotti et al. Overall and progression-free survival reported in ASCO 2018 [24]. As described by Verwaal et al., Journal of Clinical Oncology, vol. 21, no, 20, pp. 3737–3743, 2003.
