Integration of Ki67 with residual cancer burden (RCB) compared to Ki67 or RCB alone to predict long-term term outcome following neoadjuvant chemotherapy.

Abstract

535 Background: RCB and Ki67 after neoadjuvant chemotherapy have each been shown to predict long-term outcome. Their combined use might provide greater prognostic information. RCB requires collection of data beyond that in routine pathological work-up of residual disease, which may not be required when Ki67 is added. Aims: (i) To test the hypothesis that combining Ki67 and RCB as the residual proliferative cancer burden (R-P-CB) provides significantly more prognostic information than either alone. (ii) To determine if a simplified algorithm integrating Ki67 and standard characteristics of residual disease can provide as much information. Methods: Cases at the Royal Marsden Hospital between 2002-2010 were identified and residual disease assessed. The primary endpoint of the study was time to recurrence. The primary analysis compared the prognostic information from Ki67, RCB and R-P-CB. Analyses employed a Cox proportional hazards model. Prognostic indices (PIs) were also created adding Ki67, grade and ER to the RCB and AJCC staging. Leave-one-out cross validation was used to reduce bias. The overall change in chi-square (ΔX2) of the best model for each index was used to compare the prognostic ability of the different indices a ΔX2 of more than 3.84 indicates statistical significance. Results: A total of 222 evaluable patients were included in the study, median age was 50 with a median follow up of 60 months. The addition of Ki67 improved the prognostic power of all indices. The R-P-CB (ΔX2=69.5) was significantly more prognostic than the RCB alone (ΔX2=35) and Ki67 alone (ΔX2=41.4). A novel proliferative residual cancer index (PRECI) using post-treatment values of T size, number of involved lymph nodes, grade, ER status (±) and Ki67 gave ΔX2=81.1 and performed similarly to a model including the RCB, Ki67, ER and grade (ΔX2=80.2). Conclusions: Addition of Ki67 to RCB improved prediction of long-term outcome. In this study, a novel index the PRECI provided as much prognostic information as a more complex assessment involving RCB and warrants further investigation for estimating post-neoadjuvant risk of recurrence.