Habr-Gama A, Perez RO, Nadalin W, et al. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival

University of São Paulo, San Paulo, São Paulo, Brazil
Journal of Gastrointestinal Surgery (Impact Factor: 2.8). 02/2005; 9(1):90-9; discussion 99-101. DOI: 10.1016/j.gassur.2004.10.010
Source: PubMed


Neoadjuvant chemoradiation treatment (CRT) has resulted in significant tumor downstaging and improved local disease control for distal rectal cancer. The purpose of the present study was to determine the correlation between final stage and survival in these patients regardless of initial disease stage. Two hundred sixty patients with distal (0-7 cm from anal verge) rectal adenocarcinoma considered resectable were treated by neoadjuvant CRT with 5-FU and leucovorin plus 5040 cGy. Patients with incomplete clinical response 8 weeks after CRT completion were treated by radical surgical resection. Patients with complete clinical response were managed by observation alone. Overall survival and disease-free survival were compared according to Kaplan-Meier curves and log-rank tests according to final stage. Seventy-one patients (28%) showed complete clinical response (clinical stage 0). One hundred sixty-nine patients showed incomplete clinical response and were treated with surgery. In 22 of these patients (9%), pathologic examination revealed pT0 N0 M0 (stage p0), 59 patients (22%) had stage I, 68 patients (26%) had stage II, and 40 patients (15%) had stage III disease. Overall survival rates were significantly higher in stage c0 (P=0.01) compared with stage p0. Disease-free survival rate showed better results in stage c0, but the results were not significant. Five-year overall and disease-free survival rates were 97.7% and 84% (stage 0); 94% and 74% (stage I); 83% and 50% (stage II); and 56% and 28% (stage III), respectively. Cancer-related overall and disease-free survival may be correlated to final pathologic staging following neoadjuvant CRT for distal rectal cancer. Also, stage 0 is significantly associated with improved outcome.

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    • "This questions the role of surgery. In a prospective study by Habr-Gama and colleagues,57 the patients with T2–T4 tumors received 5FU-based CRT preoperatively. After eight weeks, they were reassessed and 71 out of 265 patients (26.8%) had complete clinical response, and were spared of surgery and followed up, while the rest were treated with rectal resection. "
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    ABSTRACT: In the last two decades rectal cancer has changed from a surgically managed disease into a multidisciplinary treatment model resulting in considerable improvements in the survival and outcome. This has been made possible by better understanding of the tumor biology and oncogenesis, advances in diagnostic and staging investigations, and the changing concepts in surgical excision; from the days of abdominoperineal resection to the concept of "zone of upward spread" and low anterior resection to the era of total mesorectal excision and transanal excision. Efforts are on the way to risk stratification and identification of predictors of nonoperative management. Impressive advances in the adjuvant therapies have seen a sea change in the form of postoperative radiotherapy to preoperative radiotherapy to preoperative chemoradiotherapy and postoperative adjuvant chemotherapy. This multidisciplinary approach is the key to impressive local control rates, decreased metastatic rates, overall survival, and enhancement in quality of life. Newer ideas in the understanding of genetic differences in rectal cancers have stemmed from the observation that these cancers differ in their response to the adjuvant treatment. The present day research has focused these areas of biologic differences in cancers and aims to target the specific loci in malignant cells with monoclonal antibodies directed against various growth factors, key enzyme inhibition, and genetic manipulation. The future research lies in the study of gene expression, micro-array techniques, molecular markers, and better understanding of the predictors of tumor response to therapy.
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    ABSTRACT: Cette revue retrace les étapes récentes de la recherche clinique qui ont conduit, à travers trois grandes études contrôlées, à identifier la chimioradiothérapie préopératoire comme traitement standard des cancers rectaux T3–T4 résécables. Cette approche réduit les taux de récidives locales à 6–8 %. La recherche clinique doit se poursuivre pour traiter plus efficacement la maladie micrométastatique, et pour affiner les indications de cette nouvelle thérapeutique. Preoperative chemoradiotherapy has recently been identified as standard treatment for patients with T3–T4 resectable rectal cancer, in three randomised studies. This new approach improves local control with local failure rates in the 6–8% range. New developments should aim to eradicate micrometastatic disease and define more clearly indications for preoperative chemoradiotherapy.
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