The PLCO trial 2: Flexible sigmoidoscopy in colon cancer screening [Classics Series]

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1. Screening with flexible sigmoidoscopy is associated with a significant decrease in colon cancer incidence in the distal and proximal colon

2. Screening with flexible sigmoidoscopy is associated with a significant decrease in colon cancer mortality in the distal colon only

Original Date of Publication: June 21, 2012

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large population-based randomized trial sponsored by the National Cancer Institute (NCI) to explore the effects of screening on cancer mortality. The trial has been conducted at 10 different centres across the U.S. Participants randomized to the intervention group receive active screening for PLCO cancers (i.e., chest x-ray, flexible sigmoidoscopy, CA-125, transvaginal ultrasound, PSA, digital rectal examination) in the first 6 years of the trial and are subsequently followed for another 7 years. Participants randomized to the usual care group are managed with usual medical care and are followed for 13 years. The trial began in 1993 and the screening phase of the trial was completed in 2006, though follow-up will continue until 2015. Here, we report on the findings regarding colorectal cancer screening using flexible sigmoidoscopy.

Study Rundown: Colon cancer screening with fecal occult blood testing (FOBT) has been shown to reduce colon cancer incidence and mortality. Flexible sigmoidoscopy is an endoscopic procedure whereby the most distal segment of the colon is examined. Previous studies conducted in Europe suggest that sigmoidoscopy is associated with reductions in both colon cancer incidence and mortality. The colorectal component of the PLCO trial assessed the effect of screening with two flexible sigmoidoscopies, spaced 3 or 5 years apart, on the incidence of and mortality from colon cancer in patients from the U.S. This study demonstrated that screening with flexible sigmoidoscopy was associated with a significant reduction in incidence of both distal and proximal colon cancer, regardless of the stage of the cancer, when compared to the usual-care group. Screening was also associated with a significant reduction in mortality independent of cancer stage, but only for distal colon cancer. For proximal colon cancer, screening resulted in reduced mortality for cancers staged I, II, or III, but not IV.

Study limitations include a substantial rate of endoscopy use in the usual-care group during the time the intervention group was undergoing screening – 46.5% of the usual-care group underwent either a flexible sigmoidoscopy or colonoscopy. This use may have dampened the difference in incidence and mortality between the usual-care and screening groups.

In summary, the colorectal component of the PLCO trial found that screening with flexible sigmoidoscopy was associated with decreased colon cancer mortality and incidence. The study results support routine screening with flexible sigmoidoscopy followed by colonoscopy for cases of abnormal screening results.

Click to read the study in NEJM

In-Depth [randomized, controlled study]: The PLCO cancer trial was a randomized, controlled trial that enrolled 154,900 participants between 55-74 years of age from 10 study centres in the U.S. The primary exclusion criteria were a history of PLCO cancer, ongoing cancer treatment, and lower endoscopy (i.e., flexible sigmoidoscopy, colonoscopy, or barium enema) in the previous 3 years. Of the enrolled participants, 77,445 were randomized to receive flexible sigmoidoscopy at baseline and again after 3 or 5 years, while the other 77,455 were assigned to receive usual care. The primary endpoint was death from colon cancer, while secondary endpoints included colorectal cancer incidence, cancer stage, survival, harms of screening, and all-cause mortality. The primary analysis was an intention-to-screen comparison of mortality between the two experimental groups. At a median follow-up of 11.9 years, the intervention group experienced a significant 21% reduction in colon cancer incidence compared to the usual care group (RR 0.79; 95%CI 0.72-0.85). This reduction was observed for both distal colon cancer (RR 0.71, 95%CI 0.64-0.80) and proximal colon cancer (RR 0.86; 95%CI 0.76-0.97). Additionally, there was a 26% reduction in colon cancer mortality due to screening (RR 0.74; 95%CI 0.63-0.87). This reduction was only significant for distal colon cancer (RR 0.50; 95%CI 0.38-0.64), but not proximal colon cancer (RR 0.97; 95%CI 0.77-1.22).

By Evan Chen and Andrew Cheung, MD

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