Most Breast Cancer Screening Trials Have a Flawed Design

In the present article, we discuss that why most breast cancer screening trials have a flawed origin. We suggest some solutions to correct these flaws so that more valid and reliable screening trials can be conducted in the future.     

Neoadjuvant Radiotherapy for Rectal Cancer: Meta-analysis of Randomized Controlled Trials

Background

Although neoadjuvant radiotherapy may improve local control of rectal cancer, its clinical value requires further evaluation as a result of potential side effects and advances in surgical technique. A meta-analysis was performed to assess effectiveness and safety of neoadjuvant radiotherapy in the management of rectal cancer.

Methods

The following databases were searched: the Cochrane Library, Biosis, Web of Science, Embase, ASCO Abstracts and WHO International Clinical Trials Registry Platform. Randomized controlled trials on the following comparisons were included: (1) neoadjuvant therapy versus surgery alone and (2) neoadjuvant chemoradiotherapy versus neoadjuvant radiotherapy.

Results

We identified 17 and 5 relevant trials that enrolled 8,568 and 2,393 patients, respectively. Neoadjuvant radiotherapy improved local control (hazard ratio 0.59; 95 % confidence interval 0.48–0.72) compared to surgery alone even after total mesorectal excision, whereas its benefit in overall survival just failed to reach statistical significance (0.93; 0.85–1.00). However, it was associated with increased perioperative mortality (1.48; 1.08–2.03), in particular if a dose of 5 Gy per fraction was administered (1.85; 1.23–2.78). Chemoradiotherapy improved local control as opposed to radiotherapy (0.53; 0.39–0.72), with no impact on perioperative outcome and long-term survival.

Conclusions

Neoadjuvant radiotherapy improves local control in patients with rectal cancer, particularly when chemoradiotherapy is administered. The question if the use of more effective chemotherapy protocols improves overall survival warrants further investigation.     

Insights from the Breast Cancer Screening Trials: How Screening Affects the Natural History of Breast Cancer and Implications for Evaluating Service Screening Programs

It is desirable to have a strategy for evaluation of breast cancer service screening programs years before the long‐term breast cancer mortality data are available. Since successful mammography screening has a significant impact on two components of the TNM (tumor size, node status, presence or absence of distant metastases) classification system, tumor size and node status, we investigated the effect of the randomized breast screening trials on incidence of advanced stage disease and on the subsequent breast cancer death rate. In the trials that achieved a 20% or greater reduction in advanced stage disease, there was an average breast cancer mortality reduction of 28% among women invited to screening (attenders and nonattenders combined). In the trials that achieved a reduction in advanced stage disease of less than 10%, there was no reduction in breast cancer mortality among women invited to screening. This study provides evidence that the average mortality reduction in all the trials underestimates the true mortality reduction, and that substantially greater breast cancer mortality reductions can be expected in screening programs that are effective in reducing advanced stage breast cancer. In addition, monitoring the incidence of advanced stage breast cancer in an ongoing screening program can provide a sensitive and early indicator of the subsequent mortality from the disease.     

Screening for Prostate Cancer Decreases the Risk of Developing Metastatic Disease: Findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC)

Background

Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal.

Objective

To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial.

Design, setting, and participants

Data were available for 76 813 men aged 55–69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up.

Intervention

Regular screening based on serum PSA measurements was offered to 36 270 men randomized to the screening arm, while no screening was provided to the 40 543 men in the control arm.

Outcome measurements and statistical analysis

The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease.

Results and limitations

After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p < 0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60–0.82; p = 0.001) in the intention-to-screen analysis and a 42% (p = 0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41–0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up.

Conclusions

PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases.The ERSPC trial is registered under number ISRCTN49127736.     

Postoperative Adjuvant Chemotherapy for Stage II Colorectal Cancer: A Systematic Review of 12 Randomized Controlled Trials

Background  

The impact of postoperative adjuvant chemotherapy on the oncological outcomes for stage II colorectal cancer remains controversial.     

《护理学杂志》随机对照临床试验和对照试验文献评价

目的 了解我国临床护理试验研究现状，为循证医学中心护理学领域输送基线资料。方法 按中国循证医学中心手检指南逐页手工检索《护理学杂志》刊载的随机对照临床试验（Randomized Controlled Trials,RCTs)和临床对照试验（Controlled Clinical Trials,CCTs)论文，并进行描述性统计分析和研究方法学评价。结果 共检索1986－2000年15卷85期杂志3906篇文章，其中RCTs论文147篇，CCTs论文106篇，分别占杂志创刊以来文章总刊载的3．8％和2．7％。1986－2000年RCTs论文的平均发展速度和平均增长速度分别为146．8％和46．8％，CCTs论文分别为131．6％和31．6％。结论 我国临床护理试验研究还处于起步阶段，研究方法学方面尚存在不足，有待改进。     

A Meta-Analysis of Randomized Controlled Trials that Compared Laparoscopy-Assisted and Open Distal Gastrectomy for Early Gastric Cancer

Background  

We conducted a meta-analysis to evaluate and compare the advantages of laparoscopy-assisted distal gastrectomy (LADG) over open distal gastrectomy (ODG) for treating early gastric cancer (EGC).     

Interpretation of the Randomized EVAR Trials

Purpose : Laparoscopic surgery for colon cancer has been proven safe, but controversy continues over implementation of laparoscopic technique for rectal cancer. The aim of this study was to compare the long-term outcomes of laparoscopically assisted and open surgery for nonmetastatic colorectal cancer.

Material and methods : From January 2001 to December 2006 all patients with nonmetastatic adenocarcinoma of the colon and rectum were considered for inclusion in this prospective non-randomised trial. The primary endpoint was overall survival, disease free survival and recurrence rate. Analysis was by intention to treat.

Results : A total of 365 resections were performed for nonmetastatic adenocarcinoma of the colon and rectum during the study period. Of those resections, 220 were colonic and 145 were rectal. In the patients with colon cancer 119 (54.1%) were operated laparoscopically and 101 (45.9%) by open surgery, in the patients with rectal cancer 75 (51.7%) were treated by laparoscopy and 70 (48.3%) by open technique. No statistically significant difference was found between the laparoscopic and open group regarding 5-year overall survival (p = 0.17 for colon cancer, p = 0.60 for rectal cancer), 5-year disease free survival (p = 0.25 for colon cancer, p = 0.81 for rectal cancer) and overall recurrence (p = 0.78 for colon cancer, p = 0.79 for rectal cancer). With respect to the tumor stage, in rectal cancer the probability of 5-year disease free survival was significantly higher in the laparoscopic group in stage III (p = 0.03).

Conclusion : Laparoscopic surgery for colorectal cancer is an oncologically safe procedure that is associated with a survival and recurrence rate equal to open surgery.     

A Systematic Review and Meta-analysis of the Randomized Controlled Trials on Adjuvant Intraperitoneal Chemotherapy for Resectable Gastric Cancer

Background The purpose of this systematic review and meta-analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with locally advanced resectable gastric cancer. Methods Studies eligible for this systematic review included those in which patients with gastric cancer were randomly assigned to receive surgery combined with intraperitoneal chemotherapy versus surgery without intraperitoneal chemotherapy. There were no language restrictions. After independent quality assessment and data extraction, data were pooled for meta-analysis. Results Thirteen reports of randomized controlled trials (RCTs) were included for quality appraisal and data extraction. Ten reports were judged to be of fair quality and subjected to meta-analysis. A significant improvement in survival was associated with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) alone (hazard ratio [HR] = 0.60; 95% CI = 0.43 to 0.83; p = 0.002) or HIIC combined with early postoperative intraperitoneal chemotherapy (EPIC) (HR = 0.45; 95% CI = 0.29 to 0.68; p = 0.0002). There was a trend towards survival improvement with normothermic intraoperative intraperitoneal chemotherapy (p = 0.06), but this was not significant with either EPIC alone or delayed postoperative intraperitoneal chemotherapy. Intraperitoneal chemotherapy was also found to be associated with higher risks of intra-abdominal abscess (RR = 2.37; 95% CI = 1.32 to 4.26; p = 0.003) and neutropenia (RR = 4.33; 95% CI = 1.49 to 12.61; p = 0.007). Conclusions The present meta-analysis indicates that HIIC with or without EPIC after resection of advanced gastric primary cancer is associated with improved overall survival. However, increased risk of intra-abdominal abscess and neutropenia are also demonstrated.     

United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) Randomized Controlled Trial Comparing Targeted Nodal Assessment and Ultrastaging With Standard Pathological Evaluation for Colon Cancer

OBJECTIVE:: Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC. METHODS:: In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer. RESULTS:: Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC. CONCLUSIONS:: TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.