TOTAL NEOADJUVANT THERAPY VERSUS NEOADJUVANTCHEMORADIATION IN PATIENTS WITH STAGE II-III RECTAL CANCER: IMPACT ON PATHOLOGIC COMPLETE RESPONSE, TUMOR DOWNSTAGING, AND SURVIVAL RATES.
Paolo Goffredo*1, Adil Khan2, Sarah Bell1, Xiang Gao1, Kyle Freischlag1, Pashtoon M. Kasi1, Y. Nancy You3, Imran Hassan1
1Surgery, University of Iowa, Iowa City, IA; 2Raleigh General Hospital, Beckley, WV; 3MD Anderson Cancer Center, Huston, TX
Introduction: Multi-agent systemic chemotherapy followed by chemoradiation (TNT) and single agent chemoradiation (nCRT) are accepted neoadjuvant platforms for stage II-III rectal cancer. There is a paucity of data regarding the efficacy of TNT compared to nCRT. The aim of the current study was to evaluate the impact of these two regimens on pathologic complete response (pCR), tumor downstaging (TD), and overall survival (OS).
Methods: The National Cancer Database was queried to identify patients with clinical stage II-III rectal adenocarcinoma [2006-2015]. The cohort was limited to adults who received neoadjuvant radiation with a dose of 45-70 Gy. Among these, pts were considered to have undergone TNT if they received neoadjuvant multiagent chemotherapy, and nCRT if they had both neoadjuvant and adjuvant multiagent chemotherapy. Incomplete regimens included receiving neoadjuvant single agent with or without adjuvant single agent chemotherapy. Factors associated with pCR and neoadjuvant rectal (NAR) score, calculated based on clinical T stage and pathologic T and N stages, were identified using logistic regression models. NAR <8 indicates favorable TD. The neoadjuvant component of each regimen (single vs multi-agent) was evaluated in relation to pCR and NAR. Cox regression models were used to assess the effect of prognostic factors on OS.
Results: A total of 20,041 pts were identified:15% received TNT, 27% nCRT, and 57% an incomplete regimen. In the cohort, 15% had a pCR and 22% NAR <8. After adjustment for confounders, multiagent neoadjuvant chemotherapy was not associated with higher rates of pCR compared to single agent (14 vs 16%, p=0.33). Factors independently associated with pCR were treatment at an academic facility, private insurance and higher income, and presenting with well differentiated (all p<0.01) and stage II tumors (p=0.03). Similar results were observed with low NAR as the primary endpoint. In multivariable analysis, TNT was associated with worse OS compared to nCRT (Fig 1; HR 1.35, p<0.01). Other factors independently associated with lower OS were older age, male gender, uninsured status, lower income, higher comorbidities score, poorly differentiated tumors, and positive margins (all p<0.01). In separate models, both pCR and low NAR score were associated with better OS (Fig 2).
Conclusion: In this national cohort of patients with locally advanced rectal cancer, receipt of multiagent neoadjuvant chemoradiation therapy was not associated with higher rates of pCR or low NAR scores compared to single agent based regimens. Despite the inherited limitations of this database, TNT did not have a favorable impact on OS in comparison with nCRT. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with stage II-III rectal cancer.
Figure 1.
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