Development of Second Malignancies Following Chemotherapy With or Without Radiation Therapy for the Treatment of...

We sought to identify factors associated with second pelvic malignancies (SPM), as well as second nonpelvic malignancies (SNPM), after chemotherapy with or without radiation therapy (RT) for locally advanced rectal cancer (LARC).

Patients diagnosed with stage II-III LARC. Cumulative incidence of second malignancies was analyzed using a 2-year landmark analysis with death as a competing risk.

Among 2624 patients with LARC, 460 received chemotherapy and 2164 received RT with concurrent chemotherapy (CXRT). With a median follow-up of 6 years in both cohorts, 7 SPMs were diagnosed in the chemotherapy cohort and 68 SPMs were diagnosed in the CXRT cohort. The 5- and 10-year cumulative incidence of SPM in the chemotherapy cohort were 2.3% and 4.2%, respectively, compared with 2.1% and 5.8% in the CXRT cohort (P = .3). Older age (>50) was significantly associated with development of SPM on multivariable analysis (hazard ratio [HR], 3.03; P = .005). Intensity-modulated RT was associated with reduced risk of SPM compared with conventional RT (P = .014). Of the total 75 SPMs, 72 were genitourinary cancers and only 3 were sarcomas. For SNPM, the 10-year cumulative incidence was significantly higher in the CXRT group compared with the chemotherapy group (11.0% vs 4.4%). Older age (>50) was associated with increased risk of SNPM (HR, 2.48; P < .001). Diabetes was associated with more SNPM (HR, 1.51; P = .028), whereas abstaining from tobacco was associated with decreased risk of SNPM (HR 0.63, P = .013).

The CI of SPM was not significantly higher in patients who received CXRT compared with chemotherapy alone for LARC. SNPM CI was increased in the CXRT compared with chemotherapy-alone cohort, and higher in smokers, diabetics, and patients >50 years.