A Prospective Analysis of Toxicity Associated with Intraoperative, Real-Time Planned Low Dose Rate Brachytherapy or Intensity-Modulated Radiotherapy Boost for High/Intermediate Risk Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> The ASCENDE-RT trial which used pre-planned brachytherapy boost (BT) reported worse treatment-related morbidity with BT vs dose-escalated intensity-modulated radiotherapy boost (DE-IMRT) for prostate radiation therapy (RT). However, toxicity is technique dependent and the outcomes of real-time intraoperative BT have not been well studied. We evaluate the toxicity profile of intraoperative, real-time planned BT vs DE-IMRT. <h3>Materials/Methods</h3> 402 patients treated from 2010-18 at our institution were included. Median dose for DE-IMRT was 79Gy. BT included IMRT to a median of 45Gy plus BT boost of 110 Gy. Patient-reported outcomes using the validated Prostate Cancer Symptom Indices and physician-graded CTCAE toxicity were prospectively collected from baseline to 2yrs post-RT. Clinically meaningful symptoms were defined as ≥Grade 2. Per institutional practice, an α-1 blocker is started prior to BT but not DE-IMRT boost. We report acute (0-6 months) & late (1 & 2yr) toxicity. Multivariable logistic regression calculated odds ratios (OR) for symptoms & controlled for hormone therapy, image guidance modality, risk category & age. <h3>Results</h3> At acute, 1-, & 2-yr time points 148, 108, 54 & 254, 214, 162 patients were available for BT & DE-IMRT analysis, respectively. Baseline and acute genitourinary (GU) or gastrointestinal (GI) symptoms did not differ between cohorts. For both modalities, PRO GI and GU symptom prevalence peaked acutely, declined over 1yr and returned near baseline by 2yrs (Table). At 2yrs, a difference in ≥Grade 2 CTCAE GU toxicity persisted (19% vs 2%, p = <0.001); urinary frequency (6% vs 0%, p = 0.02), & incontinence (9% vs 2%, p = 0.02) differed most. On MVA, BT had higher 2-yr GU symptoms for PRO (OR 32.0, 95%CI: 6.2-165, p < 0.0001) & CTCAE (2.2, 1.4-3.6, p = 0.0006). Cumulative incidence of CTCAE ≥Grade 3 events at 2yr were GU 3.4% vs 0%, p = 0.007 & GI 2.0% vs 2.0%, p = 1.0 for BT & DE-IMRT. <h3>Conclusion</h3> This large single institution series with prospectively collected PRO & CTCAE toxicity is one of the first to report outcomes for intraoperatively, real-time planned BT. Odds of GU symptoms ≥Grade 2 are elevated with BT but cumulative incidence of GU/GI CTCAE ≥Grade 3 toxicity at 2yr was <4% for BT & DE-IMRT. Our results may assist in counseling and suggest that among appropriately selected patients a BT boost with intraoperative planning is reasonably well tolerated.