Improved Late Rectal and Urinary Toxicity With High-Dose Intensity Modulated Radiation Therapy Using Intraprostate Fiducial Markers for Localized Prostate Cancer

Abstract

To evaluate the impact of intensity modulated radiation therapy (IMRT) with intraprostate fiducial markers on the incidence of late urinary and rectal toxicity compared to 3D conformal radiation therapy (3DCRT) for patients with prostate cancer (PC) treated in a dose-escalation protocol. The hypothesis is that IMRT with image guided radiation therapy (IGRT) allows increasing dose with less toxicity than 3DCRT. Between 1995 and 2015, 1022 consecutive patients with localized PC were treated with dose-escalation radiation therapy (RT) of which 733 patients were enrolled in this study. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up >23 months. The study included 438 patients treated with 3DCRT and 295 treated with IMRT using intraprostate gold fiducial markers IGRT. The median ICRU radiation dose was 79.8 Gy (range, 72.1-87.1), 78.7 Gy and 80.7 Gy for 3DCRT and IMRT/IGRT respectively (P<0.001). Acute and late toxicities were assessed using the EORTC/RTOG and CTCAEs v4.0 definition. A logistic regression analysis was performed to identify clinical and dosimetric prognostic factors affecting the risk of late urinary and rectal complications. Statistical analyses were carried out using statistical analysis software. The mean follow-up for the entire cohort was 75 months (range, 24-204 months). The incidence of late grade ≥ 2 urinary complications was 5.4% and 13.0% for IMRT/IGRT and 3DCRT respectively (P = 0.001) and the incidence for grade ≥ 2 rectal toxicity was 3.7% and 9.4% for IMRT/IGRT and 3DCRT respectively (P = 0.004). On multivariate analysis, the use of IMRT/IGRT (odds ratio [OR] = 0.374, P = 0.001) and the antecedent of prior transurethral resection of the prostate (OR = 2.452, P = 0.005), were the only independent factors correlated with late grade ≥2 urinary complications. Other factors like the presence of acute urinary symptoms during RT (OR = 1.780, P = 0.060) and the use of hormone therapy (OR = 0.596, P = 0.069) were of borderline statistical significance but with potential clinical relevance. The use of IMRT/IGRT (OR = 0.378, P = 0.014), the antecedent of colon diverticula (OR = 3.515, P<0.001) and the patient age (OR = 0.941, P = 0.040) were significantly correlated with late grade ≥ 2 rectal toxicity. High-dose IMRT/IGRT with intraprostatic fiducial markers is associated with a significantly lower rate of rectal and urinary side effects compared to 3DCRT in spite of higher radiation dose. Further follow up is needed to confirm the protective effect of hormone therapy on late urinary complications.