European Cancer Congress (ECC) 2015
Presented by the European Society for Medical Oncology
ECC 2015: Abstract 2002. Impact of adjuvant chemotherapy following pre-operative short course radiotherapy in stage II rectal cancer.
J. Loree, H. Kennecke, D. Renouf, H. Lim, M. Vickers, C. Speers, W. Cheung
Background: Adjuvant chemotherapy (AC) is offered to stage II rectal cancer (RCa) patients (pts) with high risk disease, but its use is frequently generalized to cases in which the probability of recurrence is low. Most prior trials evaluating the benefit of AC focused on stage II and III pts who received long course chemoradiotherapy. We examined population-based outcomes of patients with pathologic (p) stage II RCa treated with AC following pre-operative (pre-op) short course radiotherapy (SCRT) and characterized pts in whom AC provides benefit.
Materials and Methods: Eligible patients were diagnosed with stage II (pT3/4 pN0) tumors after SCRT and were referred to the 5 regional cancer centers in British Columbia between 1998 and 2009. Overall (OS), disease-specific (DSS) and relapse-free (RFS) survival were assessed with Kaplan–Meier methods. Cox regression models that adjusted for age, ECOG, gender and high risk features (T4 lesion, poor differentiation, inadequate lymph node sampling, LVI, perineural invasion, or obstruction/perforation) were constructed.
Results: Of 851 pts reviewed, 330 received pre-op SCRT of whom 123 were treated with AC (37.3%). Pts receiving AC were younger (median age 61 vs 73, P<0.0001), had better ECOG (P<0.001), and had more high risk features (P<0.0001) than those not receiving AC. Median follow up was 8.57 years in the AC arm and 7.92 years in the non-AC arm. In univariate analysis, AC was associated with improved OS (HR 0.42, 95%CI 0.30–0.59, P<0.0001), DSS (HR 0.58, 95%CI 0.36–0.94, P=0.028), and RFS (HR 0.62, 95%CI 0.39–0.98, P=0.043). In multivariate analysis, these outcomes were no longer significant (OS HR 0.62, 95%CI 0.37–1.03, P=0.064; DSS HR 0.83, 95%CI 0.43–1.61, P=0.58; RFS HR 0.82, 95%CI 0.44–1.50, P=0.51). Subgroup analysis revealed that AC only improved OS (HR 0.22, 95%CI 0.069–0.70, P=0.011) DSS (HR 0.25, 95%CI 0.07–0.89, P=0.033) and RFS (HR 0.24, 95%CI 0.07–0.85, P=0.027) in pts who had ≥2 high risk features.
Conclusions: In this population-based cohort of stage II RCa pts post SCRT, AC did not improve outcomes in unselected patients. The presence of two or more clinicopathological risk factors may identify patients who benefit from AC. Future use of biomarkers may help to refine this risk stratification.
CARE Faculty Perspective:
The use of adjuvant chemotherapy is commonly offered to individuals with clinically determined stage 2 rectal cancer who have been treated with long-course neoadjuvant chemotherapy and radiation. The aim of this study was to determine if there might be a benefit to the use of adjuvant chemotherapy for patients treated with neoadjuvant short-course radiation therapy alone and identified pathologically with stage 2 disease.
Between 1999-2009, the authors retrospectively identified 123 patients in British Columbia who were treated with neoadjuvant short-course radiation therapy and subsequently received adjuvant chemotherapy. They stratified their results according to generally accepted features of increased risk (pT4, LVI, PI, obstruction/perforation at the time of diagnosis and <12 LN identified). The vast majority received either 5FU or capecitabine alone (120 patients) and only 3 patients were treated with oxaliplatin.
Multivariate analysis controlling for age, gender, ECOG performance status as well as presence of high risk features did not demonstrate a significant difference in the outcomes of disease-specific survival, relapse-free survival or overall survival with the possible suggestion of a small signal to suggest some benefit in the subpopulation of patients with >2 high risk features. As such, in the era of modern total mesorectal excision surgery, although adjuvant chemotherapy cannot be routinely recommended to all patients with pathologically proven stage 2 rectal cancer after preoperative short-course radiation therapy, there may be a subset of patients at higher risk where such treatment might be considered.
- Dr. Robert El-Maraghi, on behalf of the CARE Oncology Faculty