Acute and Chronic Toxicity Profiles Associated with Three High-Dose-Rate Interstitial Brachytherapy Monotherapy Fractionation Schedules for Localized Prostate Cancer

Abstract

To compare the acute and chronic toxicity profiles associated with three high-dose-rate interstitial brachytherapy (HDR) monotherapy fractionation schedules: 38 Gy in 4 fractions (38/4), 24 Gy in 2 fractions (24/2), and 27 Gy in 2 fractions (27/2). 482 patients with low-risk (69%) or intermediate-risk (31%) prostate cancer were treated with Ir-192 following ultrasound-guided, percutaneous implantation of afterloading catheters. Gland volumes and pre-treatment AUA scores were similar among groups. 317 patients received 38/4 (interfraction period: 6 h or 18 h); 72 received 24/2 (interfraction period: 6 h or 14 d); 93 received 27/2 (interfraction period: 6 h or 14 d). Chi-square, t-test, ROC, and univariate analyses were conducted to compare patient characteristics, clinical outcomes, and maximal acute (<6 m following treatment) and chronic (>6 m following treatment) toxicities. Patients were treated in an HIC approved sequential dose schedule protocol with the same eligibility criteria. Clinical outcomes were similar among groups, with 3-y actuarial rates of 91% (biochemical failure-free survival), 99% (overall survival), and 100% (cause-specific survival). Acute gastrointestinal (GI) toxicities (diarrhea, bleeding, proctitis, and pain/tenesmus) were similar among groups; no grade 3 or higher toxicities were reported. Patients receiving 38/4 experienced the highest rate of acute grade 1/2 dysuria (27%), urinary retention (22%), and incontinence (6%) (p = 0.04, 0.04, 0.01). Other acute genitourinary (GU) toxicity rates were similar among all patients, including grade 3 urinary frequency/urgency (2%) and grade 3 urinary retention (<1%). Patients receiving 38/4, 25/2, and 27/2 experienced dissimilar rates of chronic grade 1/2 diarrhea (3%, 11%, 7%; p = 0.02) and rectal bleeding (7%, 4%, 0%; p = 0.02). No grade 3 or higher chronic GI toxicity was reported in any group. Chronic GU toxicity was similar among groups, with <1% of all patients experiencing grade 3 dysuria, frequency/urgency, retention, incontinence, or hematuria. Nine patients (2%) developed a urethral stricture requiring surgical dilation. Patients receiving pre-treatment hormone therapy (HT) experienced higher acute GI and GU toxicities (20% and 70%) than patients not receiving HT (10% and 53%)(p = 0.03 and 0.02). Gland volume did not predict acute or chronic toxicity. The toxicity and preliminary clinical outcomes associated with 38/4, 24/2, and 27/2 are comparable. These data suggest that accelerated, hypofractionated HDR constitutes a well tolerated, convenient, and effective treatment modality. Additional follow-up to characterize long-term outcomes is warranted.