Early-stage clear cell ovarian cancer compared to high-grade histological subtypes: An outcome exploratory analysis in two oncology centers

Gynecol Oncol. 2021 Jan;160(1):64-70. doi: 10.1016/j.ygyno.2020.10.014. Epub 2020 Oct 17.


Objective: advanced stage clear cell ovarian cancer (CCOC) carries a higher risk of relapse and death compared to other histological subtypes. The prognosis of early-stage CCOC is controversial.

Methods: Early-stage high-grade OC patients from two Italian oncologic centers were included. Patients with early-stage CCOC were compared with those with high-grade endometrioid (HGE) and serous (HGS) OC in terms of relapse-free interval (RFI), cancer-specific survival (CSS) and post relapse cancer-specific survival (prCSS). The Cox proportional hazard model and the restricted mean survival time were used.

Results: Between 1981 and 2012, 134 patients with CC, 152 with HGE and 160 with HGS were treated at two referral centers. Median follow-up was 11.5 years. Ten years RFI rates were 80.6%, 72.1%, 60.6%, and CSS rates were 84.3%, 82.6%, 81.7% respectively. Adjuvant chemotherapy significantly improved RFI (aHR 0.61, 95%CI 0.40 to 0.91, P = 0.015). In the multivariable analysis HGS histotype was associated with a shorter RFI compared to CC, (Hazard Ratio [HR]: 1.81; 95%CI: 1.12-2.93; P = 0.016), whereas CSS was not statistically different. prCSS was longer in HGS compared to CCOC (HR, 0.36; 95% CI, 0.17-0.74; P = 0.006). According to the stage, IA/IB/IC1 HGSOC had a shorter RFI (HR, 2.13; 95% CI, 1.14-3.99; P = 0.018) compared to IA/IB/IC1 CCOC, but similar CSS. For prCSS, CC compared to HGS conferred a worse prognosis regardless of the initial stage.

Conclusions: Early-stage CCOC is associated with a longer RFI, similar CSS and a shorter prCSS compared to HGSOC. No prognostic differences were observed between CC and HGE OC. The relapse risk was the lowest in IA/IB/IC1 CC compared to HGS, whereas CC displayed poor sensitivity to chemotherapy after relapse.

Keywords: Clear cell ovarian cancer; Early-stage ovarian cancer; High-grade endometrioid ovarian cancer; High-grade serous ovarian cancer.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Clear Cell / pathology*
  • Adenocarcinoma, Clear Cell / surgery
  • Adult
  • Carcinoma, Endometrioid / drug therapy
  • Carcinoma, Endometrioid / mortality
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Endometrioid / surgery
  • Chemotherapy, Adjuvant
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / pathology
  • Cystadenocarcinoma, Serous / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Italy / epidemiology
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / surgery
  • Prognosis
  • Treatment Outcome