The impact of age at the time of radiotherapy for localized prostate cancer on the development of second primary malignancies

Abstract

Purpose: There is a known increased risk of second primary malignancy (SPM) in patients with prostate cancer (CaP) treated with radiotherapy (RT). It is unclear how age at diagnosis influences the risk of SPMs.

Materials and methods: Using the 1973 to 2013 Surveillance, Epidemiology, and End Results Program, we studied the impact of age on SPMs (defined as a bladder or rectal tumor) after localized CaP treatment with radical prostatectomy (RP) or RT. SPM risk was compared using inverse probability of treatment weighting (IPTW)-adjusted cumulative incidence function and competing-risk proportional hazard models. Overall survival (OS) in patients with SPM was compared using Kaplan Meier and Cox regression analyses.

Results: A total of 579,608 patients met inclusion criteria, and 51.8% of the cohort was treated with RT. The 10- and 20-year cumulative incidences of competing risk (IPTW adjusted) of SPMs were 1.9% (95%CI = 1.8-1.9%) and 3.6% (95%CI = 3.4-3.7%) after RP vs. 2.7% (95%CI = 2.6-2.8%) and 5.4%(95%CI = 5.3-5.6%) after RT. IPTW-adjusted competing risk hazard ratio (HR) of SPM after RT compared to RP was increased in the entire cohort (HR 1.46; 95%CI = 1.39-1.53, P < 0.001) and was highest in the youngest patients: Age <55 HR = 1.83 (95% confidence interval [CI] = 1.49-2.24, P<0.001), Age 55 to 64 HR = 1.66 (95%CI = 1.54-1.79, P < 0.001), Age 65-74 HR = 1.41 (95%CI = 1.33-1.48, P < 0.001), Age ≥75 HR = 1.14 (95%CI = 0.97-1.35, P = 0.112). At 10 years, SPM-specific mortality occurred in 28.9% of patients treated with RT, though OS with SPM was worse in the youngest patients: Age <55 HR = 1.88 (95%CI = 1.25-2.81, P = 0.002), Age 55-64 HR = 1.60 (95%CI = 1.42-1.81, P < 0.001), Age 65-74 HR = 1.40 (95%CI = 1.30-1.52, P < 0.001), Age ≥ 75 HR = 1.27 (95%CI = 1.06-1.53, P = 0.009). All of the age categories had similar median follow-up times.

Conclusion: At 10 years there is a 1.8% increased incidence of SPM after RT compared to RP, of which <30% of RT-treated patients with an SPM die as a result of a SPM. However, the risk of SPMs was greatest among younger men treated with RT for localized CaP, and this relationship could not be explained solely by follow-up time, latency time, or life expectancy. An improved understanding of those at the highest risk of SPMs may help tailor treatment and surveillance strategies.

Keywords: Abbreviations used: SPM, second primary malignancy; Age factors; BT, brachytherapy; CI, confidence interval; CSS-SPM, cancer specific survival of a SPM; CaP, prostate cancer; EBRT, External beam radiotherapy; HR, hazard ratio; IPTW, inverse probability of treatment weighting; IRR, incidence rate ratios; OS, overall survival; Prostatectomy; Prostatic neoplasms; RP, radical prostatectomy; RR, relative risks; RT, radiotherapy; Radiotherapy; SEER, Surveillance, Epidemiology and End Results Program registry; SIR, standardized incidence ratios; Second primary neoplasms; Survival analysis.