Elsevier

The Lancet Oncology

Volume 8, Issue 7, July 2007, Pages 625-633
The Lancet Oncology

Review
Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer

https://doi.org/10.1016/S1470-2045(07)70202-4Get rights and content

Summary

The past decade has seen pronounced changes in the treatment of locally advanced rectal cancer. Historically, the standard of care involved surgery followed by adjuvant radiotherapy or chemoradiotherapy. More recently, the emergence of neo-adjuvant chemoradiotherapy has fundamentally changed the management of patients with locally advanced disease. In clinical trials, pathological complete responses of up to 25% have raised the question as to whether surgery can be avoided in a select cohort of patients. A trial of omission of surgery for selected patients with complete response after preoperative chemoradiotherapy has shown favourable long-term results. In this article, we outline emerging factors for achieving pathological complete response, non-operative strategies to date, methods for prediction of response to chemoradiotherapy, and future directions with the addition of MRI as a radiological guide to complete response.

Introduction

More than 13 000 people are diagnosed with rectal cancer in the UK each year. In three-quarters of cases, the disease will be localised to the primary site. For these patients, surgical resection will constitute the cornerstone of treatment. Many patients with T3, T4, and node-positive rectal cancers will be referred for preoperative chemoradiotherapy (CRT) to reduce the risk of local failure and to ensure negative margins at surgery.

In a landmark study, Habr-Gama and colleagues1 presented long-term results of avoidance of surgery for selected patients with radiological and clinical evidence of complete response after neoadjuvant CRT. Long-term follow-up confirmed the safety of this approach. Modern rectal surgery is not without morbidity, and many patients wish to avoid the permanent stoma associated with abdominoperineal excision. However, preoperative treatments have developed to such a degree that pathological complete responses (pCR) can reach 25% at the time of surgery. With the premise that a pCR might represent needless surgery, an understanding both of the factors that contribute to achieving pCR, and of methods that predict response to CRT, might aid the safe selection of appropriate patients for omission of surgery after CRT (figure 1).

Section snippets

Preoperative versus postoperative CRT

Postoperative radiotherapy or CRT has been the standard of care for many years for stage II and III rectal cancer.2, 3, 4, 5 As a result, pCR cannot be considered a relevant endpoint in assessing the effect of this approach. Postoperative radiotherapy has several theoretical disadvantages. For example, residual neoplastic cells within a hypoxic postoperative tumour bed are poorly oxygenated and, therefore, their sensitivity to radiation is decreased. Furthermore, when surgery preceeds

Factors affecting pathological complete response

The process of tumour response to CRT, or downstaging (the process of reduction in T or N stage after preoperative treatment), is dependent on many factors. Each of these factors must be considered individually when reviewing response rates in treatment protocols, and when designing preoperative or non-operative strategies.

Omission of surgery for complete responders to preoperative treatment

The impressive incidence of pCR in recent trials raises the possibility of selecting patients who have a clinical complete response to preoperative treatment and avoiding surgery. Long-term results have been reported by Habr-Gama and colleagues1 on omission of surgery for selected patients with radiological and clinical evidence of complete response after neoadjuvant CRT.

265 patients with distal resectable rectal tumours were treated with preoperative CRT from 1991 to 2002. Radiotherapy was

Prediction of response to preoperative treatment

At present there is no reliable technique for predicting clinical or pathological complete tumour response after CRT. Limited data exist for each potential modality in this regard. The greatest challenge for non-operative strategies is patient selection. Therefore, the most promising modalities for prediction of true complete response need to be considered.

Future directions

With up to 25% of patients having a pCR after neoadjuvant CRT, there is a compelling argument for attempting to avoid surgery in carefully selected groups of patients, especially if surgery involves a permanent colostomy. Although the study by Habr-Gama and colleagues1 is extremely promising, a systematic prospective trial using modern imaging techniques has not been carried out.

At the Royal Marsden Hospital (Sutton, Surrey, UK) and Pelican Cancer Foundation (Basingstoke, Hampshire, UK), a

Conclusion

The work of Nigro and colleagues65 in the 1970s has led to the acceptance of radical CRT as the standard of care for squamous-cell carcinoma of the anus. Thus, the leap of faith needed to believe in non-operative strategies for rectal cancer is significant, although not unprecedented in gastrointestinal oncology. Surgery remains the standard of care after neoadjuvant CRT irrespective of the extent of response, but results from a rigorous controlled trial using modern imaging techniques will be

Search strategy and selection criteria

Data for this review were identified by searches of PubMed and references from relevant articles, using the search terms “rectal cancer”, “complete response”, and “radiotherapy”. Abstracts and reports from meetings were included only when they related directly to previously published work. Only papers published in English between 1983 and 2007 were included.

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