CRC Outcomes Better When First of Multiple Cancers

Colorectal cancer (CRC) survival is longer when it’s the first of multiple primary malignancies than when it’s the second or solo, new data suggest.

The findings came from a retrospective analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database of more than half a million people in the US with primary CRC. They were divided into three groups: Group A, with CRC as their only malignancy; group B, with CRC as the first with one or more subsequent primary malignancies; and group C, with CRC as the second of multiple primary malignancies.

The finding that Group B had the highest 5-year survival of the three groups is novel and surprised the authors, but they have some theories to explain it.

“We potentially thought group A would do the best, seeing as they only had one type of cancer. But what we found…is that [group B] actually had the best survival outcome. It could have something to do with the tumor characteristics at a molecular biological level, or potentially because of increased surveillance from having colorectal cancer first,” first author Anjelli Wignakumar, MD, told Medscape Medical News.

On the other hand, those in group A tended to be younger and to present with more aggressive disease, although they still fared better than did those in group C. “There are lots of potential explanations,” said Wignakumar, a clinical research fellow in Colorectal Department, Cleveland Clinic, Weston, Florida.

Clinically, the takeaway is for comprehensive screening for other types of cancer in people with primary cancers, and in particular screening for CRC in people with other primary cancers. “Depending on the patient’s family history and other things, increasing that screening hopefully increases our risk of picking up something earlier,” she said.

Of the total 592,063 patients with CRC in SEER from 2000-2020, 71.8% were in group A, 11.9% in group B, and 16.3% in group C. Group B included a higher proportion of men (57.1% vs 51.8% and 53.1% for A and C, respectively; P < .001). Group A was significantly younger at CRC presentation (65.7 years vs 67.3 years and 72.6 years, for B and C, respectively; P < .001).

Those in group A were more likely to have elevated pretreatment tumor marker carcinoembryonic antigen (49.7% vs 43.2% and 46.9%, in B and C, respectively; P < .001) and presented more often with liver metastases (17.5% vs 7.4% and 12.1%, respectively; P < .001) or lung metastases (6.3% vs 2.5% and 4.2%, respectively, P < .001).

Right-sided CRC, which has been associated with worse survival compared to left-sided, was more common in group C (38.6%), while left-sided colonic cancer, associated with better survival, was more common in group B (37.9%). Both were significant compared to the other groups (P < .001).

Surgical treatment was recommended significantly (P < .001) more often for group B (20.5%) than for groups A (13.0%) or C (14.3%), while systemic adjuvant therapy was given significantly (P < .001) more often to those in group A (29.0%) than groups B (27.8%) or C (21.3%).

Compared to group B, overall 5-year mortality hazard ratios were 1.26 for group A, which could be attributed to their more advanced disease, the authors said. Those in group C also had higher 5-year mortality (1.66). Those were both statistically significant, with similar trends for cancer-specific mortality.

Mean 5-year survival was 50.4 months for group B, significantly (P < .001) longer than the 41.8 months for group A and 39.2 months for group C. 

In their discussion in the paper, Wignakumar and colleagues presented a variety of hypotheses about the findings, including that group B might have a distinct immune profile that “enhances their ability to survive multiple cancers and potentially improve their responsiveness to treatment.” 

Alternatively, “Patients who develop a second primary cancer have already demonstrated resilience, having endured the physical and emotional challenges of their initial cancer treatment. This experience may reflect a stronger baseline health status and the benefits of previous successful interventions, contributing to potentially better survival outcomes compared with those facing cancer for the first time.” 

Wignakumar had no disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social.