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

Abstract

a b s t r a c tObjective. There is a need to develop and validate biomarkers for treatment response and survival in tuboovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into Gynecologic Oncology 154 (2019) 441-448 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 N6-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CRS and progression free and overall survival (PFS and OS).Results. 877 patients were included from published and unpublished studies.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 b 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.• The Chemotherapy response score (CRS) assesses histological effect in ovarian cancer after neoadjuvant chemotherapy (NACT). • The CRS is associated with progression-free and overall survival.• CRS could provide useful information to estimate a patient's probability of early vs. late relapse.• The CRS is an appealing primary endpoint in clinical trials as a surrogate for survival as it can be measured earlier. • We recommend the CRS be incorporated as an endpoint in clinical trials of novel therapeutic agents that have a NACT arm.

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

“…Since its description, the CRS has been independently validated in several studies,66–69 including an individual patient data meta-analysis incorporating results from over 800 patients from different centres worldwide 70. This system has been recommended for use in the ICCR guidelines for tubal and ovarian carcinomas,19 since a numerical score allows objective reporting and comparison of results and is thus superior to descriptive reporting (see Table 3).…”

WITHDRAWN: Up-Regulation of HDAC6 Results in Poor Prognosis and Chemoresistance in Patients with Advanced Ovarian High-Grade Serous Carcinoma

“…The clinicopathological characteristics of these patients were reviewed, including age, recurrence, progression-free survival (PFS), overall survival (OS), FIGO stage, treatment methods, surgical status (complete or incomplete resection), response evaluation criteria in solid tumors (RECIST) status [19], and chemotherapy response score (CRS) [20,21]. The RECIST was used to stratify patients according to the following responses: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) by using computed tomography before and after chemotherapy [19].…”

“…The RECIST was used to stratify patients according to the following responses: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) by using computed tomography before and after chemotherapy [19]. Based on omental examination results, CRS was used to classify patients as follows: patients with CRS of 3 had a complete/near complete response; those with CRS of 2 had a partial response; and those with CRS of 1 had no or minimal response [20,21].…”

Role of the pathologist in assessing response to treatment of ovarian and endometrial cancers

“…Of these, 80 harboured BRCA 1/2 germline mutations; those with BRCA 1/2 mutations were more likely to show CRS3. 12 The predictive ability of CRS scoring could allow selection of women with CRS3 to receive additional maintenance therapy such as PARP inhibitors, potentially resulting in longer PFS, as shown in the SOLO1 trial. 13 The CRS score has been independently validated in several countries.…”