Pelvic radiotherapy was associated with modest excess secondary uterine cancer risk

KEY POINTS

• The SEER analysis included female five-year survivors diagnosed between 2000 and 2022 with localized or regional rectal, bladder or lower-pelvic cancers. The final cohorts included 35,815 rectal, 10,016 bladder and 14,559 lower-pelvic cancer patients.
• Secondary uterine cancer was defined as a new malignancy of the uterine corpus or cervix arising at least five years after the primary cancer. External-beam radiotherapy was compared with no radiotherapy, with death treated as a competing event.
• Twenty-year cumulative incidence after radiotherapy versus no radiotherapy was 2.59% versus 0.84% for rectal cancer, 1.46% versus 0.41% for bladder cancer and 2.30% versus 0.80% for lower-pelvic cancers.
• Despite large relative differences, the corresponding absolute excess risks were only 1.75, 0.99 and 1.50 percentage points, respectively. Secondary uterine cancer developed in 211 versus 116 rectal, 5 versus 30 bladder and 95 versus 40 lower-pelvic cancer survivors in the radiotherapy and non-radiotherapy groups.
• In multivariable competing-risk analyses, radiotherapy remained independently associated with secondary uterine cancer after rectal cancer (hazard ratio 2.17; 95% confidence interval, 1.49–3.15) and bladder cancer (2.82; 95% confidence interval, 1.06–7.48), but not after lower-pelvic cancer.
• Excess risk was driven predominantly by uterine corpus rather than cervical cancer. Standardized incidence ratios after radiotherapy were 3.04 for rectal cancer, 3.19 for bladder cancer and 2.69 for lower-pelvic cancers compared with the general population.
• Risk was delayed, with secondary cancers appearing most commonly at approximately 90 months. The rectal-cancer hazard ratio peaked at 3.93 during 120–179 months, while the bladder estimate reached 5.34 during the same interval, although only five radiotherapy-associated bladder events occurred.

CLINICAL TAKEAWAY

SOURCE

Radiotherapy and Oncology