Second malignancy probabilities in prostate cancer patients treated with SBRT and other contemporary radiation techniques

Abstract

Background: Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). However, relative SM probabilities following treatment with contemporary radiation techniques such as stereotactic body radiotherapy (SBRT) or moderately hypofractionated intensity modulated radiotherapy (HF-IMRT) remain unknown.

Methods: A cohort analysis was performed of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up comparing SM probability amongst men receiving either radical prostatectomy (RP), conventionally fractionated intensity-modulated radiotherapy (CF-IMRT), HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models, which were used to generate predicted probabilities. Additionally, propensity score-adjusted pairwise assessments of modalities were performed.

Results: For 303,432 patients included in the study, median follow-up was 9.08 years (IQR 7.01-11.21). Predicted rates of SM by treatment modality and adjusted odds ratios (AOR) for development of SM (referent: RP) were: 6.0% for RP (AOR n/a), 7.1% for CF-IMRT (AOR 1.20, 95%CI 1.14-1.25, P < 0.001), 7.3% for HF-IMRT (AOR 1.25, 95%CI 1.01-1.55, P = 0.045), 6.6% for BT (AOR 1.11, 95%CI 1.07-1.16, P < 0.001), and 5.7% for SBRT (AOR 0.95, 95%CI 0.81-1.12, P = 0.567). On propensity score-adjusted analysis, SBRT was associated with lower odds of SM compared to CF-IMRT (AOR 0.78, 95%CI 0.66-0.93, P = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95%CI 0.73-1.03, P = 0.102).

Conclusions: Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy but not stereotactic body radiotherapy were associated with increased probability of a second malignancy compared to radical prostatectomy. Patients treated with SBRT may be at lower risk of second malignancy due to improved conformality, radiobiological differences or patient selection. The possibility that SBRT in select patients may minimize the probability of SM underscores the need for assessment of second malignancy risk in prospective studies of SBRT.

Keywords: External beam radiation therapy; Prostate cancer; Prostate radiotherapy; SBRT; Secondary malignancy.