Patients with prostate cancer who receive radiotherapy have a higher risk of second primary cancer, according to a study published in JAMA Network Open.

Patients treated with radiotherapy had a greater risk of second primary cancer when compared with patients who underwent surgery or surveillance.

The researchers noted, however, that the overall risk of second primary cancer was low, with or without radiotherapy.

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For this retrospective study, researchers analyzed data on 143,886 patients from the Veterans Affairs Corporate Data Warehouse. Patients had been diagnosed with localized prostate cancer from 2000 through 2015. At baseline, the median age was 65 (range, 60-71) years. 

In the year after their prostate cancer diagnosis, 36.8% of patients received primary radiotherapy. Among patients who did not receive radiotherapy, 34.3% underwent surgery, and 65.7% were managed with active surveillance, medical management, or observation.

The median follow-up was 9 years. The primary outcome was the diagnosis of a second primary cancer at least 1 year after the prostate cancer diagnosis. 

The rate of second primary cancer was 3.0% overall, 3.7% in patients who received radiotherapy, and 2.5% in patients who did not. 

The increased risk of second primary cancer with radiotherapy was significant in a multivariate analysis, with risk increasing as the time from diagnosis increased. The hazard ratio (HR) at 1 to 5 years after prostate cancer diagnosis was 1.24 (95% CI, 1.13-1.37; P <.001), which increased to 1.50 for years 5 to 10 (95% CI, 1.36-1.65; P <.001) and to 1.59 for years 10 to 15 (95% CI, 1.37-1.84; P <.001), then stabilized at 1.47 for years 15 to 20 (95% CI, 1.08-2.01; P =.02).

Other factors significantly associated with an increased risk of developing a second primary cancer were older age at prostate cancer diagnosis and the presence of comorbidities. Black race and a later year of prostate cancer diagnosis were associated with a lower risk of second primary cancer.

The most common second primary cancers in the radiotherapy and non-radiotherapy cohorts were bladder cancer, leukemia, lymphoma, and rectal cancer. 

“Overall, the incidence and risk of developing a second primary cancer were relatively low in both groups,” the researchers concluded. “Although the long-term toxic effects of radiotherapy are important to discuss when counseling patients on the risk-benefit profile of prostate radiotherapy, they need not deter physicians from recommending radiotherapy if appropriate.”


Bagshaw HP, Arnow KD, Trickey AW, et al. Assessment of second primary cancer risk among men receiving primary radiotherapy vs surgery for the treatment of prostate cancer. JAMA Netw Open. Published online July 28, 2022. doi:10.1001/jamanetworkopen.2022.23025