Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer

Dept. of Surgery 2K12 1C, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium, B-9000.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 01/2009; 2(1):CD006041. DOI: 10.1002/14651858.CD006041.pub2
Source: PubMed


Patients with cancer of the rectum, the end part of the large bowel immediately above the anus, are treated with surgery. When the tumour is deemed to present a high risk of recurrence after surgery, a course of radiotherapy (RT) is administered before the operation. It has been proven in clinical studies that this 'preoperative' radiotherapy improves the outcome in rectal cancer patients. Recently, several studies have investigated the combination of radiotherapy with chemotherapy (CRT) before surgery. In theory, adding chemotherapy enhances the antitumour activity of radiotherapy. This meta-analysis has summarized the results of five studies that compared preoperative RT alone with preoperative CRT in rectal cancer patients. All of these studies were randomized, which means that the decision to administer either RT or CRT was determined by chance (ballot draw). The results of the meta-analysis may be summarized as follows. Compared to RT alone, preoperative CRT leads to increased side effects during treatment. Also, postoperative complications are somewhat increased, although the risk of dying from postoperative complications is similar. Preoperative CRT is more effective in causing tumour shrinkage (downstaging), and in preventing local recurrence of the disease. However, addition of chemotherapy did not result in more sphincter preserving surgeries, and did not affect the overall survival in rectal cancer patients.

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    • "The putative benefits of the addition of chemotherapy concurrent with either pre- or postoperative RT include local RT sensitization and systemic control of disease (eradication of micrometastases). Also, preoperative chemoRT has the potential to increase the rates of pathologic complete response and sphincter preservation [26, 27, 28, 29, 30, 31, 32]. "
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    ABSTRACT: A major outcome of importance for rectal cancer is local control. Parallel to improvements in surgical technique, adjuvant therapy regimens have been tested in clinical trials in an effort to reduce the local recurrence rate. Nowadays, the local recurrence rate has been reduced because of both good surgical techniques and the addition of radiotherapy. Based on recent reports in the literature, preoperative chemoradiotherapy is now considered the standard of care for patients with stages II and III rectal cancer. Also, short-course radiotherapy appears to provide effective local control and the same overall survival as more long-course chemoradiotherapy schedules and, therefore, may be an appropriate choice in some situations. Capecitabine is an acceptable alternative to infusion fluorouracil in those patients who are able to manage the responsibilities inherent in self-administered, oral chemotherapy. However, concurrent administration of oxaliplatin and radiotherapy is not recommended at this time. Radiation therapy has long been considered an important adjunct in the treatment of rectal cancer. Although no prospective data exist for several issues, we hope that in the near future, patients with rectal cancer can be treated by using the best combination of surgery, radiation therapy, and chemotherapy in near future.
    Annals of Coloproctology 08/2014; 30(4):165-74. DOI:10.3393/ac.2014.30.4.165
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    • "Colorectal cancer is the third most common malignancy presenting serious threat to human health worldwide, and one-third is represented by rectal cancer, which accounts for approximately 40% of all colorectal cancer deaths [1]. Currently, preoperative 5-fluorouracil (5-FU) based neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) surgery has been adopted as a standardized multidisciplinary treatment for stage II– III rectal cancer [2]. However, the response to nCRT varies greatly, ranging from pathological complete regression (PCR) to complete resistance [3]. "
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    ABSTRACT: This study aimed to clarify the role of multidrug resistance-associated protein 3 (MRP3) in resistance to neoadjuvant chemoradiotherapy and long-term prognosis of advanced rectal cancer. Immunohistochemistry was used to measure MRP3 expression in biopsy specimens of 144 stage II-III rectal cancer patients who received preoperative chemoradiotherapy. The effect of MRP3 expression on short-term pathological response and postoperative long-term prognosis were assessed using the Cox proportional hazards model. Short interfering RNAs targeting MRP3 were synthesized and used to transfect human colorectal carcinoma cell lines. The effect of MRP3 down-regulation on cell proliferation and apoptosis in response to 5-fluorouracil and/or irradiation were examined in vitro and in xenograft mouse models, respectively. The content of intracellular reactive oxygen species and the activity of caspase-3-dependent apoptotic pathway in response to irradiation were further evaluated. High expression (immunoreactive score > 6) of MRP3 significantly predicted poor pathological response to chemoradiotherapy (tumor regression grade <= 2 vs. >= 3, p = 0.002) in univariate analysis and unfavorable long-term prognosis (5-year overall survival: HR = 1.612, 95% CI, 1.094-2.375, p = 0.016; 5-year disease-free survival: HR = 1.513, 95% CI, 1.041-2.200, p =0.030) in multivariate Cox analysis. MRP3 down-regulation significantly increased 5-fluorouracil or irradiation-induced cell apoptosis and attenuated tumor growth following irradiation in animal models. MRP3 inhibition significantly reduced intracellular reactive oxygen species exporting from cells following irradiation, and increased expression of cleaved poly ADP-ribose polymerase and caspase-3. Aberrant expression of MRP3 in rectal cancer confers chemo-radioresistance. MRP3 might be a predictive factor and an attractive target in treating advanced rectal cancer.
    Cancer Letters 07/2014; 353(2). DOI:10.1016/j.canlet.2014.07.025 · 5.62 Impact Factor
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    • "For advanced rectal cancer, neoadjuvant radiochemotherapy (RCT) has been proven to reduce the rate of local recurrence in comparison to postoperative treatment [1] or preoperative radiotherapy alone [2,3]. German guidelines state exact treatment rules for UICC stage I to III and localization of cancer in the rectum [4] depending on the local tumor stage at initial tumor diagnosis. "
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    ABSTRACT: Neoadjuvant radiochemotherapy has been proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases in standard protocols of neoadjuvant radiochemotherapy. The present study aimed at addressing the effects of an intensified neoadjuvant radiochemotherapy on long term cancer related and disease free survival. A total of 387 patients underwent oncologic resection for rectal cancer in our institution between January 2000 and December 2009. There were 106 patients (27.4%) who received an intensified radiochemotherapy protocol completely and without excluding criteria (study group). A matched pair analysis was performed by comparing the study group with patients undergoing primary surgery and postoperative radiochemotherapy, if necessary and possible (control group). Matching was carried out in descending order for UICC stage, R-status, tumor height, T-, N-, V-, L-, M- and G-category of the TNM-system according to the histopathological staging. Follow-up data included local recurrence rate, cancer related and disease free survival. In the study group histopathological work-up of the specimen revealed a treatment response in terms of tumor regression in 92.5% (98/106) of these patients. Undergoing intensified neoadjuvant RCT the actuarial cancer related and disease free survival was 67.9% and 70.4%, local recurrence was 5.7% after an observation period of 4.3 +/- 2.55 years. In the control group cancer related and disease free survival was 71.7% and 82.7%, local recurrence was 4.7% after an observation period of 3.8 +/- 3.05 years revealing no statistical significant difference between the two groups. Moreover, estimated 5-year results of cancer related survival (66.7 vs 67.9 (controls)), the disease free survival (66.7 vs 79.9 (controls)) as well as subgroup analysis of UICC 0-III and UICC IV patients showed no difference between the study and control group as well. In our study, intensified neoadjuvant radio-chemotherapy shows a high rate of tumor regression. The resulting inferior histopathological tumor stage shows the same long term local control and systemic tumor control as the control group with a primary more favorable tumor stage.
    BMC Cancer 08/2013; 13(1):388. DOI:10.1186/1471-2407-13-388 · 3.36 Impact Factor
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