A 3-Tier Grading System and Mitotic Count Predict for Outcome in Ovarian Carcinoma Treated with Neoadjuvant Chemotherapy
K Rahimi, C Ma, H Begley, V Nair, B Rosen, S Chin, H MacKay, PA Shaw. University Health Network, Toronto, ON, Canada
Background: Debulking surgery followed by adjuvant platinum based chemotherapy is the standard of care for advanced stage ovarian cancer. Preoperative chemotherapy may be offered to patients with non-debulkable disease, poor performance scores and co-morbidities, and retrospective analyses indicate no difference in survival for patients matched for age, stage, and grade. The histologic features associated with neoadjuvant chemotherapy are known, but correlation between tumor features at interval debulking and patient outcome has not been reported. The aim of this study is to identify histologic criteria in chemotherapy exposed tumor tissue that correlate with outcome, and possibly predict for acquired platinum resistance.
Design: The study population included 75 patients treated with preoperative chemotherapy followed by interval surgical debulking. Number of treatment cycles, debulking status, disease-free interval (RFS), and overall survival (OS) were recorded. Two pathologists reviewed at least one representative section of each tumour, blinded to clinical outcome. Histologic features assessed included Silverberg score/grade, mitotic count, nuclear, cytoplasmic, and stromal changes. Predictive value was determined by univariate Cox Proportional-Hazards regression.
Results: The mean age of patients at diagnosis was 60.3 (range 34 to 84 years). Optimal debulking was achieved in 48% of patients. High grade serous carcinoma was the predominant histologic type (n=71), with a Silverberg grade of 3 in 18.1% (n=13), and grade 2 in 75% (n=54). High Silverberg grade (OS p=0.02; RFS p = 0.0005) and high mitotic count (OS p=0.007; RFS p=0.0004) were significant predictors of both lower recurrence free and lower overall survival with univariate analysis. Younger patients at the time of diagnosis (p=0.006) and high architecture score (p=0.03) were significant for lower recurrence free survival. Debulking status and number of preoperative cycles were not significant predictors of outcome in this series (p > 0.05).
Conclusions: Results of this preliminary study indicate careful histologic evaluation of residual disease resected following neoadjuvant chemotherapy has predictive value, and should include the 3-tier, Silverberg grade and mitotic count.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 162, Monday Morning