Pathological Chemotherapy Response Score in Patients Affected by High Grade Serous Ovarian Carcinoma: The Prognostic Role of Omental and Ovarian Residual Disease

Abstract

Background: The chemotherapy response score (CRS) has emerged as a simple and reproducible histopathological grading system for assessing chemotherapy response in patients affected by ovarian high-grade serous carcinoma. Objective: To evaluate the prognostic impact of histological tumor response in ovarian and omental surgical specimens from patients with advanced stage ovarian high-grade serous carcinoma. Study Design: A cohort of 161 women were identified from the database of Department of Gynecology, “Fondazione Policlinico Universitario Agostino Gemelli IRCCS” of Rome, Italy between January 2014 and December 2017 with a follow-up of 65 months. All the omentum, the ovarian tissue and peritoneal samples, defined as “other sites,” were reviewed by gynecological pathologists to assign a CRS of 1–3 to the omentum and ovarian sites and a score of 0–1 to the peritoneal tissue. The Cox proportional hazards regression and the log-rank test were used to assess the survival pattern and the prognostic value of the CRS adjusting for age and stage. The Kaplan-Meier method was applied to estimate the progression free and overall survival. Results: The evaluation of adnexal disease showed significant differences in PFS, both in univariate and in multivariate analyses. On PFS univariate analysis, ovCRS1 vs. ovCRS3: HR, 2.27; 95% CI, 1.37–3.77; p = 0.001; ovCRS2 vs. ovCRS3: HR, 1.83; 95% CI, 1.03–3.23; p = 0.04, and on PFS multivariate model ovCRS1 vs. ovCRS3; HR, 2.53; 95% CI, 1.5–4.24; p = 0.001 and ovCRS2 vs. ovCRS3; HR, 1.90; 95% CI, 1.08–3.37; p = 0.03. Regarding the omental residual disease, as expected, CRS showed a significant prognostic value for OS and PFS; in detail the median PFS of patients with CRS1, 2 and 3 was 15, 15, and 22 months, respectively, the median OS was 41 and >50 months, respectively. Moreover, the univariate analysis for OS suggested that in our cohort the “other sites” score of 0 was significantly associated with an improvement in overall survival compared to score 1. Conclusions: We demonstrated for the first time the prognostic significance of adnexal CRS confirming also the prognostic role of omental CRS.

The Added Value of CA125 Normalization Before Interval Debulking Surgery to the Chemotherapy Response Score for the Prognostication of Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy for Advanced Disease

“…Second, as information about BRCA 1/2 mutations was not available in most of the included patients, we could not conduct a more detailed subgroup analysis. Third, although the PFS of our cohort was in line with that of previous reports [16,18], the follow-up period in the present study was relatively short, and the median OS was not reached. Finally, the sample size of this work is limited.…”

“…In the 2019 European Society for Medical Oncology (ESMO) ovarian cancer guidelines, a three-tiered chemotherapy response score (CRS) system was recommended for patients receiving NACT to evaluate tumor response and predict prognosis [15]. Since its description, the CRS system has been independently assessed in many studies [16][17][18][19][20][21]. Currently, it is considered an accurate and highly reproducible method to predict survival outcomes for patients with tubo-ovarian high-grade serous carcinoma (HGSC) [15].…”

Identification of Ovarian Cancer Patients Most Likely to Achieve Chemotherapy Response Score 3 Following Neoadjuvant Chemotherapy: Development of a Predictive Nomogram

“…The CRS system is the only method that is recommended in ESMO-ESGO guidelines for ovarian cancer patients to predict PFS and OS following NACT-IDS ( 3 ). Its reproducibility and accuracy have been validated in numerous studies ( 10 – 13 , 15 ). The omental response to NACT that was graded with the scoring system was reported to be even more important than debulking status for the prognosis of patients.…”

“…Recently, Böhm proposed a three-tiered chemotherapy response score (CRS) system based on the pathological examination of residual disease on omental specimens ( 9 ). Since its description, many studies have assessed the CRS independently and consistently validated it as a highly reproducible method to predict progression-free survival (PFS) and platinum sensitivity ( 10 – 15 ) for patients with tubo-ovarian high-grade serous carcinoma (HGSC). A recent meta-analysis by the HGSC CRS Collaborative Network confirmed that CRS 3 was significantly associated with improved OS ( 11 ).…”

BRD4 Inhibition by AZD5153 Promotes Antitumor Immunity via Depolarizing M2 Macrophages

“…Notably, in BET inhibitortreated mice, a significant decrease in PD-L1 expression was observed in macrophages isolated from ovarian tumor (17). Santoro et al indicated that the chemotherapy response score of neoadjuvant chemotherapy is a prognostic marker involving fibro-inflammatory change in TME (47). Furthermore, Grabosch et al demonstrated that neoadjuvant chemotherapy with cisplatin enhanced tumor immunogenicity and upregulated PD-L1 expression in ovarian cancer mouse models.…”