Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

Gynecol Oncol. 2019 Aug;154(2):441-448. doi: 10.1016/j.ygyno.2019.04.679. Epub 2019 May 19.

Abstract

Objective: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.

Methods: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS).

Results: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45-0·66; P < 0·001) and 0·65 (95% CI 0·50-0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027).

Conclusions: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.

Keywords: Chemotherapy response score; High-grade serous tubo-ovarian cancer; Neoadjuvant chemotherapy; Prognosis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Carboplatin / therapeutic use*
  • Disease-Free Survival
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / mortality
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Humans
  • Neoadjuvant Therapy
  • Neoplasms, Cystic, Mucinous, and Serous / drug therapy*
  • Neoplasms, Cystic, Mucinous, and Serous / mortality
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Carboplatin