Multi-parametric MRI guided dose escalated radiotherapy for treatment of localized prostate cancer (PCa): Initial toxicity results of a prospective phase II trial.

Abstract

25 Background: Multi-parametric MRI (mpMRI) of PCa uses advanced sequences to detect aggressive, high grade and bulky lesions. Given known advantages of hypofractionated radiotherapy (RT) to treat PCa (low a/b ratio), we conducted a phase II trial to escalate a high dose to mpMRI lesion(s) via Image-Guided (IG)-RT/Volumetric Arc Therapy (VMAT)/Stereotactic Body Radiotherapy (SBRT) technology. We present the acute toxicity results of this novel approach. Methods: 22 pts with mpMRI lesion(s) were prospectively treated to a course of IGRT/VMAT to the prostate & seminal vesicle +/- pelvic lymph nodes (PLN) to a dose of 45 Gy in 25 fractions followed by SBRT boost, 18 Gy in 3 fraction to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions (EQD2 = 85.2 Gy using a/b 3 or 93.4 Gy using a/b 1.5) to the mpMRI prostatic lesion(s). Placement of 3 polymer based fiducial markers visible in both CT and MRI for image co-registration and treatment guidance was performed. Genitourinary (GU) and gastrointestinal (GI) adverse events (AE) were scored using CTCAE v4. DSMC approved reporting of acute AE results prior to completion of trial accrual as an interim safety assessment prior to final trial accrual. Results: Median age was 66.5 years (range: 57-80). All patients had PI-RADS grade 3-5 mpMRI lesion(s); 41.0%, 45.4% and 13.6% having 1, 2 and 3 lesions respectively. Ten (45%) pts had Gleason Score (GS) 8-10 and 12 had GS 7 disease. Median PSA was 8.97 (range: 4.0-77.9). Eleven (50%), 10 (46%), and 1 (5%) pts had stage T1, T2, and T3 tumor, respectively. Nine pts received treatment to the PLN and 15 received androgen deprivation therapy. All patients completed the protocol treatment without reporting acute GI or GU AEs grade ≥3 during treatment or at follow up. Grade 2 GI (diarrhea) and GU toxicity (frequency) was seen in 2 (9%) and 9 (41%) pts, respectively, during treatment. Of the 16 pts (71%) with least 3 months follow-up all grade 2 GI and 55.5% GU toxicities had resolved. Conclusions: Early results of this prospective Phase II study suggest that high-dose RT for localized PCa via mpMRI-guided RT/VMAT and SBRT boost is tolerable with a favorable acute toxicity profile.