Elsevier

Clinical Colorectal Cancer

Volume 17, Issue 4, December 2018, Pages 320-330.e5
Clinical Colorectal Cancer

Original Study
Short-Course Radiotherapy in Neoadjuvant Treatment for Rectal Cancer: A Systematic Review and Meta-analysis

https://doi.org/10.1016/j.clcc.2018.07.014Get rights and content

Abstract

Background

To assess whether preoperative short-course radiotherapy (PSRT) could be the treatment of choice compared to preoperative long-course chemoradiotherapy (PLCRT)

Methods

The PubMed, Embase, and Web of Science Databases were searched to conduct a systematic review and meta-analysis. Perioperative and survival outcomes between PSRT and PLCRT were selected as end points for our meta-analysis. In addition, health-related quality-of-life outcomes were also systematically reviewed between PSRT and PLCRT. Finally, we also reviewed evidence of optimized regimens of PSRT (with delayed surgery or adding consolidation chemotherapy).

Results

PLCRT showed a better pathologic complete response (pCR) rate (odds ratio = 0.05, 95% confidence interval = 0.02-0.18, P < .01), but this benefit did not translate into a higher sphincter preservation rate (odds ratio = 1.62, 95% confidence interval = 0.72-3.67, P = .25) or other perioperative outcome differences. In terms of survival outcomes, adding either PLCRT or PSRT both showed obvious advantages for local control compared to surgery alone, and PSRT and PLCRT had similar long-term outcomes irrespective of pairwise or network meta-analyses. Moreover, on the basis of health-related quality-of-life scores, PSRT and PLCRT also had no overall differences. Systematic review of current evidence indicates that the insufficiency of PSRT on pCR might be improved by delayed surgery or adding consolidation chemotherapy.

Conclusions

PSRT could be the treatment of choice compared to PLCRT when pCR is not the primary aim. PSRT with delayed surgery or adding consolidation may provide further possibilities for the future evolution of neoadjuvant therapies.

Introduction

Chemotherapy, radiotherapy, and surgery have been the primary methods for treating rectal cancer over the past decades.1, 2 On the basis of the National Comprehensive Cancer Network (NCCN) Clinical Practical Guidelines in Oncology,3 there are 2 primary neoadjuvant regimens accepted as standard for rectal cancer patients: preoperative long-course radiotherapy (PLRT) with concomitant chemotherapy (PLCRT) and preoperative short-course radiotherapy (PSRT). Both treatments are effective for local control and carry a low morbidity. PSRT is more accepted in northern Europe, whereas PLCRT enjoys more support in the United States and the rest of Europe.4

Whether PSRT or PLCRT is the preferred regimen has been a continuous topic of debate,4, 5, 6, 7 and 2 famous randomized controlled trials (RCTs) comparing PSRT and PLCRT have been performed.8, 9 Notably, a published investigation indicated that only 55% of rectal cancer patients received “standard” PLCRT in the United States, according to the National Cancer Data Base.10, 11 This result calls into question the PLCRT regimen. For patients, this situation could be partly explained by the higher cost and lower compliance seen for PLCRT.12 Although currently PLCRT may not require chemotherapy infusion devices, because oral capecitabine is often being used, increased 5-fold radiotherapy schedule time and associated costs in managing additional acute toxicity were issues that remained for patients who received PLCRT.5 For clinicians, does this indicate that we should reappraise this as the standard therapy? Robust evidence is needed to define an optimal, simple, and equivalent neoadjuvant therapy pattern.

Accordingly, to explore whether PSRT can be an alternative choice compared to conventional PLCRT for rectal cancer patients, we performed a comprehensive meta-analysis based on perioperative, long-term, and health-related quality-of-life (HRQL) outcomes. In addition, we explored whether optimized PSRT regimens could advance the future evolution of neoadjuvant therapies.

Section snippets

Search Strategy

Searches were conducted of the PubMed, Embase, and Web of Science databases (for studies published up to August 2017) to identify all relevant studies (restricted to those written in the English language). The following search algorithm was used in PubMed: (rectal) AND (neoadjuvant OR preoperative OR preoperatively) AND (chemotherapy OR radiotherapy OR irradiation OR radiation OR chemoradiotherapy OR chemoradiation OR radiochemotherapy). Furthermore, if multiple studies were published on the

Characteristics of Included Studies

A total of 18,573 relevant studies (8846 from PubMed and 9727 records from other databases) were initially identified on the basis of our systematic study search strategy. After removing duplicates from multiple databases, 9326 studies remained for screening. After screening the title and abstracts, 58 studies remained for further evaluation. Finally, data from 19 studies based on 14 different trials were included for meta-analysis.9, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,

Discussion

Over the past decades, PLCRT and PSRT have been developed in parallel and are regarded as the 2 main standards of care for patients with high-risk rectal cancer. In general, PSRT is preferred in Northern Europe and PLCRT in Southern Europe and America. The primary advantage of PSRT is its lower toxicity, because it does not require concomitant chemotherapy in the radiotherapy regimen, as seen in with PLCRT. In addition, the delivery of PSRT is less expensive because it can be administered in 5

Conclusion

PSRT showed comparable perioperative, long-term, and HRQL outcomes compared to PLCRT. Although PLCRT has a better pCR effect, this benefit does not translate into a higher sphincter preservation rate. When pCR is not the primary aim for surgeons and patients, PSRT seems to be the better option for the preoperative treatment of rectal cancer patients because of its main advantages of simplicity and lower cost. Furthermore, optimized PSRT regimens could improve the current deficiencies on tumor

Disclosure

The authors have stated that they have no conflict of interest.

Acknowledgments

We thank the department of Surgical Oncology of First Hospital of China Medical University and the College of China Medical University for technical assistance. Supported in part by the Special Prophase Program for National Key Basic Research Program of China (2014CB560712); Clinical Capability Construction Project for Liaoning Provincial Hospitals (LNCCC-A01-2014); and the Doctoral Scientific Research Startup Foundation of Liaoning Province (201601138).

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  • Cited by (0)

    B.M. and P.G. contributed equally to this work as first authors.

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