The survival benefit of screen-detected colorectal cancer (CRC) versus non-screen-detected cancer is driven by factors beyond the known screening effect of earlier stage at diagnosis.

A new study comprised more than 4,000 patients aged 50-74 years, and therefore eligible for the National Bowel Cancer Screening Program (NBCSP), diagnosed with CRC between June 2006 and June 2020.

The study, published in JNCI Cancer Spectrum, compared patient, tumour, treatment, and outcome data for cancers detected by FOBT within the national screening program and those detected outside the NBCSP.

Most patients (87.2%) in the cohort were diagnosed outside the NBCSP after presenting with symptoms or as an incidental finding during investigations for an unrelated condition.

The study found screen-detected CRC was most often located in the left colon whereas the highest proportion of non-screen detected CRC was located in the rectum.

As has been previously demonstrated, there was more early-stage CRC in the screen-detected group than the non-screen detected group – stage 1 (38.5% v 17.4%), stage II (21.1% v 28.5%), stage III (28.3% v 26.5%) and stage IV (5.5% v 20.6%).

“Compared with non-screen-detected cancers, screen-detected CRC was more often reported to be well or moderately differentiated (76.3% vs 66.4%, OR = 1.65, 95% CI = 1.24 to 2.19; P < 0.001) and less frequently had mucinous differentiation noted (16.1% vs 19.7%, OR = 0.66, 95% CI = 0.51 to 0.87; P = 0.002).”

The study found stage I screen-detected CRC was more often T1 compared with stage I non-screen-detected CRC (66.5% vs 43.4%, OR = 2.78, 95% CI ¼ 1.93 to 4.00; P < 0.001).

Similarly, stage III screen-detected colon cancers were more often T1 or T2 rather than T3 or T4 compared with stage III non-screen-detected colon cancers.

“Stage III screen-detected colon cancers also had lower rates of N2 disease (19.1% vs 31.1%, OR = 0.52, 95% CI ¼ 0.33 to 0.84; P = 0.007) and were less likely to have other high-risk features than stage III non-screen-detected colon cancers (36.9% vs 50.8%, OR = 0.57, 95% CI = 0.37 to 0.87; P = 0.009)

The study also noted differences in patient and treatment characteristics between the two groups of patients.

Screen-detected patients were slightly younger (mean 62.4 v 64.2 years; P < 0.001) and more medically fit (OR for ASA score 1-2 = 1.91; P <0.001).

“OS was better in younger and fitter patients, those with left-sided disease and early-stage disease, and those without poor differentiation, mucinous histology, or lymphovascular invasion present in their histological specimen,” the study said.

As well, relapse-free survival and overall survival were more favourable in patients with screen-detected CRC including in a stage-matched analysis.

The study reported that the primary tumour was resected more frequently in the screen-detected group (93.9% v 88.4%, OR = 2.01, 95% CI = 1.36 to 2.99; P < 0.001) and patients who relapsed or were de novo stage IV more often underwent metastatic resection if their primary cancer was initially screen detected (46.2% vs 25.1%, OR = 2.57, 95% CI = 1.46 to 4.45; P < .001).

Stage III screen-detected colon cancer patients more often received adjuvant chemotherapy (95.7% vs 87.3%, OR = 3.58, 95% CI = 1.52 to 8.36; P = 0.002) and more often received oxaliplatin-based chemotherapy (82.9% vs 71.7%, OR = 2.27, 95% CI = 1.34 to 3.92, P = 0.002) than non-screen-detected stage III colon cancer patients.

“Overall these differences in multidisciplinary care are also likely to be contributing to the superior survival of stages III and IV screen-detected patients,” the study said.

The researchers, including senior investigator Professor Peter Gibbs from the Personalised Oncology Division at Walter and Eliza Hall Institute, said their findings had likely clinical implications.

“Stage II screen-detected patients had numerically better 5-year OS rates (97%) than non-screen-detected stage I patients (92%), suggesting that screen-detection could be a marker of stage II patients who should not be offered adjuvant chemotherapy because of the already excellent prognosis.”

As well, in some of the stage III screen-detected patients including those with T4 or N2 disease, three months of adjuvant therapy may be sufficient.

“Further studies will be needed before future adjuvant chemotherapy decision making and surveillance strategies factor in the method of detection as part of an increasingly complex risk stratification mode,” they concluded.