Adjuvant chemotherapy does not appear to increase the risk of second cancers for patients with stage III-IV colon cancer, a new study suggests. 

However, researchers did observe a greater risk of second cancers among patients who received FULFOL (folinic acid and fluorouracil) than among those who received FOLFOX (folinic acid, fluorouracil, and oxaliplatin). 

The most common second cancers were prostate, colon, breast, lung, rectal, and uterine cancers. These findings were published in Clinical Colorectal Cancer.

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To determine patterns of second cancer development among patients with stage III-IV colon cancer, researchers analyzed data from the cancer registry of the Regensburg Tumor Center in Eastern Bavaria, Germany. 

The study cohort included patients diagnosed with colon cancer between 2002 and 2018. Patients were evaluated for second cancers after at least 6 months from the start of chemotherapy, given after R0 resection of the primary tumor and any metastatic lesions. 

There were 2856 patients who had stage III (2576 patients) or stage IV (280 patients) colon cancer, of whom 1520 (53.2%) received chemotherapy after resection. 

The use of chemotherapeutic regimens changed over time, with FUFOL initially being the most common first-line regimen, and FOLFOX later dominating in first-line treatment.

A multivariable analysis suggested that, at a median follow-up of 73.2 months, overall survival was better for patients who received chemotherapy than for those who did not (adjusted hazard ratio [HR], 0.576; 95% CI, 0.511-0.649; P <.001). 

Second cancers occurred in 7.8% of patients, and the 5-year cumulative rate of second cancers was 8.9%. The most common second cancers were prostate cancer (18.4%), colon cancer (16.1%), breast cancer (8.1%), lung cancer (8.1%), rectal cancer (4.9%), and uterine cancer (4.9%).

Second cancers were identified in 9.5% of patients who had received postoperative chemotherapy and 5.8% of those who had not. The 5-year cumulative rates were 8.8% and 9.0%, respectively, and this difference was not statistically significant (HR, 0.944; 95% CI, 0.716-1.245; P =.685). 

An analysis of second cancers by chemotherapy regimen showed that FOLFOX was associated with a lower 5-year cumulative rate of second cancer than FULFOL — 6.1% and 13.9%, respectively (P <.001). 

“A significantly increased risk for subsequent second cancer after adjuvant chemotherapy was not detected,” the researchers summarized. “Interestingly, second cancer rate was decreased in patients treated with FOLFOX compared to FUFOL. The findings may have an impact on the surveillance and long-term follow-up of cancer patients.”


Teufel A, Li M, Gerken M, et al. Second cancer after additive chemotherapy in patients with colon cancer. Clin Colorectal Cancer. Published online July 15, 2022. doi:10.1016/j.clcc.2022.07.002