Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta‐analysis

Abstract

Combining chemotherapy with preoperative radiotherapy (RT) has a sound radiobiological rationale. We performed a systematic review and meta-analysis of trials comparing preoperative RT with preoperative chemoradiation (CRT) in rectal cancer patients. The Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline (Pubmed) were searched from 1975 until June 2007. Dichotomous parameters were summarized using the odds ratio while time to event data were analyzed using the pooled hazard ratio for death. From the primary search result of 324 trials, 4 relevant randomized trials were identified. The addition of chemotherapy significantly increased grade III and IV acute toxicity (p 5 0.002) while no differences were observed in postoperative morbidity or mortality. Preoperative CRT significantly increased the rate of pathological complete response (p < 0.001) although this did not translate into a higher sphincter preservation rate (p 5 0.29). The local recurrence rate was significantly lower in the CRT group (p < 0.001). No statistically significant differences were observed in disease free survival (p 5 0.89) or overall survival (p 5 0.79). Compared to preoperative RT alone, preoperative CRT improves local control in rectal cancer but is associated with a more pronounced treatment related toxicity. The addition of chemotherapy does not benefit sphincter preservation rate or long-term survival. Future trials should address improvements in the rate of distant metastasis and overall survival by incorporating more active chemotherapy. ' UICCKey words: rectal cancer; radiotherapy; surgery The incidence of fatal cases of colorectal cancer in Europe exceeds 200,000 per year. 1 Because of the specific anatomy and biology of rectal cancer, surgery alone historically has been associated with local recurrence in up to 1 in 4 patients. 2 Locally recurrent disease is usually incurable, causes important morbidity and suffering and gives rise to systemic metastases. In the last few decades, improvements in surgical technique have dramatically lowered the incidence of locally recurrent disease. Careful pathological studies have clearly demonstrated that the major cause of local recurrence is the persistence of tumor foci within the mesorectum. 3,4 Intact removal of the entire mesorectum (total mesorectal excision or TME) in cancers of the mid or lower third of the rectum was pioneered by Heald and has resulted in local recurrence rates lower than 5-10%. [5][6][7] Parallel to improvements in surgical technique, adjuvant therapy regimens have been tested in clinical trials in an effort to reduce local recurrence rates. Neoadjuvant radiotherapy (RT) has been shown to significantly decrease local recurrence rate and improve survival provided a biologically equivalent dose (BED) of at least 30 gray (Gy) is administered. 8 The advantages of preoperative over postoperative RT include enhanced effectiveness in well-oxygenated tissue, downstaging of advanced tumors and better treatment compliance. 9 The theoretical ...

Benefits of Neoadjuvant Hypofractionated Radiotherapy in the Treatment of Locally Advanced Adenocarcinomas

“…Contrary to the belief that reduction in local recurrence after radiation increases the likelihood of overall survival, no significant effect in terms of overall survival was found from SRT approach compared with selective postoperative radiation ± chemotherapy [17]. The result was similar with prior meta-analyses [11][12][13][14]. This finding seems to be reasonable, considering the following facts.…”

“…The Colorectal Cancer Collaborative Group and Wong et al conducted literature-based meta-analyses that focused on preoperative radiation, and they found beneficial effects on local control compared to surgery alone [11,12]. Then, meta-analyses by De Caluwé et al and Ceelen et al demonstrated that preoperative CRT improves local control in resectable stage II and III rectal cancer compared to preoperative RT alone [13,14]. Nevertheless a metaanalyses by Chen et al based on eight randomized controlled trials involving 6894 patients found that short course radiotherapy substantially reduced the risk of local recurrence compared with surgery alone or selective postoperative radiation ± chemotherapy, also this effect is also comparable when compared with long course chemo Although SRT has been shown to marginally improve survival over surgery alone in this meta-analysis, it must be emphasized that the Swedish trial was the only included trial that reported a significant improvement in survival, and there was evidence of heterogeneity across the included studies [16].…”

Adjuvant chemotherapy for rectal cancer: Is it needed?

“…Since majority of the patients in the West nowadays receive neoadjuvant chemoradiotherapy, the most pertinent question regarding the benefit of postoperative chemotherapy remains unanswered by the studies described above. In light of several systematic reviews reporting no benefit of neoadjuvant chemoradiotherapy when compared to radiotherapy alone in terms of disease free and overall survival, the role of postoperative chemotherapy has come into question [30,31] . Five recent European trials (CHRONICLE, QUASAR, EORTC 22921, PROCTOSCRIPT, ICNRRT) enrolling 3143 patients with stage Ⅱ and Ⅲ rectal cancer investigated the benefits of postoperative chemotherapy after neoadjuvant chemoradiotherapy and surgery (Table 1) [10,12,3234] .…”

Phase I/II Study of Preoperative Concurrent Chemoradiotherapy with S-1 for Locally Advanced, Resectable Rectal Adenocarcinoma

“…The local control benefit of preoperative radiotherapy remains relevant even in the era of total mesorectal excision [3]. The addition of chemotherapy to preoperative conventional long-term radiotherapy has been demonstrated to be feasible, with enhanced tumoricidal effects [4]. The protracted venous infusion of 5-FU during radiotherapy has demonstrated substantial advantages over bolus 5-FU administration in an adjuvant setting and has been extrapolated to preoperative strategies [5].…”