Histopathologic response to neoadjuvant chemotherapy as a prognostic biomarker in tubo-ovarian high-grade serous carcinoma: updated Chemotherapy Response Score (CRS) results

Abstract

ObjectiveThe Chemotherapy Response Scoring (CRS) system was developed to enable reproducible reporting of histologic tumor response in interval debulking specimens following neoadjuvant chemotherapy in advanced stage tubo-ovarian high-grade serous carcinoma. This prognostic biomarker has been included in ovarian cancer pathology reporting guidelines (International Collaboration on Cancer Reporting, College of American Pathologists) and in the upcoming European Society for Medical Oncology-European Society of Gynaecological Oncology (ESMO-ESGO) guidelines for ovarian cancer management. We present follow-up data on the CRS validation initiatives and suggest research with novel therapeutic agents incorporating this biomarker.MethodsThe cohort on whom CRS was originally developed was analyzed after an extended follow-up of an additional 36 months. The CRS histopathologic scoring system was applied to omental sections obtained at interval surgery from all 80 patients. Progression-free and overall survival were re-calculated.ResultsAfter a median follow-up of 4.3 years the CRS score predicted progression-free survival with an HR of 0.39 (95% CI 0.21 to 0.70), p = 0.002 adjusted for age, stage, and debulking status (median 1.08 vs 2.27 years for CRS1/2 vs CRS3). CRS was also predictive of overall survival with an HR of 0.17 (95% CI 0.07 to 0.44), p = 0.0002 adjusted for age, stage, and debulking status (median 2.55 vs 5.47 years for CRS1/2 vs CRS3).ConclusionCRS3 is a reproducible prognostic biomarker for improved progression-free and overall survival in stage 3C or 4 tubo-ovarian high-grade serous carcinoma after neoadjuvant chemotherapy. The score, obtained at interval debulking surgery, can help facilitate research and biomarker driven first-line treatment of patients with advanced ovarian cancer.

A Modified 2 Tier Chemotherapy Response Score (CRS) and Other Histopathologic Features for Predicting Outcomes of Patients with Advanced Extrauterine High-Grade Serous Carcinoma after Neoadjuvant Chemotherapy

“…The 3 tier CRS system was proposed in 2015 and recently recommended by ICCR and CAP in ovarian cancer pathology reporting guidelines [ 3 , 7 ]. Subsequently, several studies have further examined this system and correlated it with prognosis [ 4 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

“…Recently, the International Collaboration on Cancer Reporting (ICCR) recommended and the College of American Pathologists (CAP) endorsed a 3 tier CRS system for assessing cases of advanced extrauterine HGSC after NACT [ 7 ]. This tool is being used in some institutions but has yet to be accepted as routine clinical practice.…”

“…In addition, the prognostic significance of the CRS system is still controversial. The CRS of omental tumor samples has been reported to correlate with progression-free survival (PFS) [ 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], but its predictive value for overall survival (OS) has differed among studies [ 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 ]. In addition, a wide range of conflicting results have been seen for the predictive value of CRS in adnexal tumor samples [ 10 , 12 , 13 , 14 ].…”

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

“…This cohort was re‐analysed after a further follow‐up period of 36 months. The results showed that patients with CRS 3 had a significantly better PFS and OS …”

“…The results showed that patients with CRS 3 had a significantly better PFS and OS. 10 In terms of its prognostic significance, the CRS system functions as a binary score, with CRS3 characterising a patient cohort with favourable outcomes. The differences observed for PFS and OS between CRS1 and CRS2 were not statistically significant.…”