Dataset Information

Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data.

ABSTRACT:

Background and purpose

The role of preoperative short-course radiotherapy (SCRT) in rectal cancer treatment, when compared to long-course radiochemotherapy (LCRT), is still controversial. Thus the meta-analysis with trial sequential analysis (TSA) was performed to evaluate the long-term survival of SCRT and LCRT as therapeutic regimens for locally advanced rectal cancer.

Material and methods

PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to August 2017 for eligible studies. Hazard ratios (HRs) or odds ratios (ORs) of overall survival (OS), disease free survival (DFS) and local recurrence (LR) with the corresponding 95% confidence intervals (CIs) were calculated and TSA was applied.

Results

11 studies with 1984 patients were included. There was no significant difference in OS (HR = 0.92, 95% CI: 0.75-1.13, p = 0.44), DFS (HR = 0.94, 95% CI: 0.79-1.12, p = 0.50) and LR (OR = 0.73, 95% CI: 0.49-1.08, p = 0.11) between SCRT and LCRT groups. TSA suggested firm evidence for lacking on average a -10% relative risk reduction (RRR) in 4-year OS but no statistical significance in 4-year DFS.

Conclusions

Preoperative SCRT is as effective as LCRT for locally advanced colorectal cancer in long-term survival. SCRT could be preferential while facing long waiting lists or lacking medical resource.

SUBMITTER: Wang X

PROVIDER: S-EPMC6042715 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data.

Wang Xin X Zheng Bobo B Lu Xinlan X Bai Ruhai R Feng Linlin L Wang Quan Q Zhao Yan Y He Shuixiang S

PloS one 20180712 7

<h4>Background and purpose</h4>The role of preoperative short-course radiotherapy (SCRT) in rectal cancer treatment, when compared to long-course radiochemotherapy (LCRT), is still controversial. Thus the meta-analysis with trial sequential analysis (TSA) was performed to evaluate the long-term survival of SCRT and LCRT as therapeutic regimens for locally advanced rectal cancer.<h4>Material and methods</h4>PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to ...[more]

PMID: 30001375

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Project description:BACKGROUND: The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control. METHODS AND DESIGN: Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4-6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function). DISCUSSION: Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach.

Project description:ImportanceAlthough both short-course radiotherapy and long-course chemoradiotherapy have been practiced in parallel for more than 15 years, no cost-effectiveness analysis comparing these 2 approaches in patients with locally advanced rectal cancer has been published.ObjectiveTo analyze the cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy for the treatment of patients with locally advanced rectal cancer.Design, setting, and participantsThis economic evaluation used a cost-effectiveness model simulating 10-year outcomes for 1 million hypothetical patients aged 65 years with locally advanced rectal cancer treated with either short-course radiotherapy or long-course chemoradiotherapy, followed by surgery and chemotherapy. Utilities and probabilities from the literature and costs from the Healthcare Bluebook and Medicare fee schedules were used to determine incremental cost-effectiveness ratios. It was assumed that long-course chemoradiotherapy would result in higher rates of low anterior resection (LAR). To model preference-sensitive care, a 2-way sensitivity analysis was conducted in which the utilities of the no-evidence-of-disease (NED) states with LAR and abdominoperineal resection (APR) were simultaneously varied. The analysis was repeated for patients with distal rectal tumors. Analysis was conducted from January to October 2018.ExposuresShort-course radiotherapy and long-course chemoradiotherapy.Main outcomes and measuresIncremental cost-effectiveness ratios.ResultsShort-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy (incremental cost-effectiveness ratio, $133 495 per quality-adjusted life-year). Two-way sensitivity analysis revealed that the cost-effective approach for a given patient depended on the utilities for the NED-LAR and NED-APR states. Assuming that a greater proportion of patients with locally advanced distal tumors undergoing long-course chemoradiotherapy (39%) would proceed to LAR compared with those treated with short-course radiotherapy (19%), long-course chemoradiotherapy was the cost-effective approach (incremental cost-effectiveness ratio, $61 123 per quality-adjusted life-year).Conclusions and relevanceShort-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy for patients with locally advanced rectal cancer. The cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy was sensitive to the utilities of the NED-LAR and NED-APR health states, highlighting the importance of care that is sensitive to patient preference. Long-course chemoradiotherapy was the cost-effective approach for patients with distal tumors.

Project description:Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer.Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life.Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.ClinicalTrials.gov NCT01558921.

Dataset Information

Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data.

Background and purpose

Material and methods

Results

Conclusions

Publications

Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data.

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