Second Primary Cancer Risk After Primary Radiotherapy vs Surgery or Other Treatment in Veterans With Localized Prostate Cancer

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In a retrospective cohort study reported in JAMA Network Open, Bagshaw et al found that the risk of a second primary cancer at more than 1 year from diagnosis was significantly greater among U.S. veterans with localized prostate cancer who received primary radiotherapy vs those who received surgery or other types of treatment or management.

Study Details

The study involved data from the Veterans Affairs Corporate Data Warehouse on 143,886 eligible patients with no cancer history diagnosed with localized prostate cancer (T1–T3) between January 2000 and December 2015. A total of 52,886 patients (36.8%) received primary radiotherapy within 1 year after diagnosis, and 91,000 (63.2%) did not receive primary radiotherapy. Among the latter, 31,218 patients (34.3%) received a surgical procedure without radiotherapy and 59,782 patients (65.7%) received active surveillance, medical management, or observation. The primary outcome measure was diagnosis of a second primary cancer more than 1 year after prostate cancer diagnosis.

Key Findings

Median follow-up was 9 years (interquartile range = 6–13 years). A second primary cancer diagnosis at more than 1 year after prostate cancer diagnosis occurred in a total of 4,257 patients (3.0%), comprising 1,955 patients (3.7%) in the radiotherapy cohort and 2,302 patients (2.5%) in the nonradiotherapy cohort.

On multivariable analysis, patients in the radiotherapy cohort had a significantly greater risk of second primary cancer vs those in the nonradiotherapy cohort at years 1 through 5 after diagnosis (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.13–1.37, P < .001), with increased  risk observed during the subsequent 15 years: hazard ratios were 1.50 (95% CI = 1.36–1.65, P < .001) for years 5 to 10, 1.59 (95% CI = 1.37–1.84, P < .001) for years 10 to 15, and 1.47 (95% CI = 1.08–2.01, P = .02) for years 15 to 20.

The most frequent types of second primary cancer in the radiotherapy cohort were bladder cancer (1.8% of all patients vs 1.1% of all patients in the nonradiotherapy cohort), leukemia (0.7% vs 0.5%), lymphoma (0.4% vs 0.3%), and rectal cancer (0.4% vs 0.3%).

Among all patients, age at diagnosis (HR = 1.03 per additional year of age, 95% CI = 1.03–1.03, P < .001) and higher Prostate Cancer Comorbidity Index score (HR for 3–4 vs 0 = 1.12, 95% CI = 1.01–1.24, P = .04; HR for ≥ 5 vs 0 = 1.19, 95% CI = 1.11–1.28, P < .001) were associated with increased risk of second primary cancer; Black vs White race (HR = 0.76, 95% CI = 0.71–0.83, P < .001), and later vs earlier year of diagnosis (HR = 0.99 per additional year, 95% CI = 0.98–1.00, P = .04) were associated with reduced risk.

The investigators concluded: “In this cohort study, patients with prostate cancer who received radiotherapy were more likely to develop a second primary cancer than patients who did not receive radiotherapy, with increased risk over time. Although the incidence and risk of developing a second primary cancer were low, it is important to discuss the risk with patients during shared decision-making about prostate cancer treatment options.”

Hilary P. Bagshaw, MD, Department of Radiation Oncology, Stanford University, is the corresponding author for the JAMA Network Open article.

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