Timing of High-Dose-Rate Brachytherapy With External Beam Radiation Therapy in Patients With Intermediate- and...

High-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) are effective treatments for prostate cancer but cause genitourinary (GU) and gastrointestinal (GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients. The primary objective was to assess differences, if any, in the incidence of grade (G) 3 or higher GU toxicities from treatment. We also aimed to explore the incidence of G1 to G4 GI toxicities, quality of life (QOL), and patient satisfaction. Suppression of prostate-specific antigen (PSA) and signals for survival differences were also analyzed.

This was a single-center randomized trial in patients with intermediate- and high-risk localized prostate cancer who received HDR-BT before (Arm A) or after (Arm B) EBRT. Toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE). The International Prostate Symptom Score (IPSS) was used to assess lower urinary tract symptoms. The International Index of Erectile Function scale (IIEF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) were used to assess erectile dysfunction and QOL at 0, 3, 9, and 12 months.

Fifty patients were recruited to each arm, with 48 and 46 patients completing treatment and follow-up in each arm, 81.5% of whom had high-risk disease. There were no G3 or G4 GU or GI toxicities. G1 urinary frequency was the most common adverse event experienced in both arms, peaking in incidence 3 months after treatment commenced (45.7% and 42.2% in Arm A and B, respectively). Up to 11% of patients reported G1 urinary frequency at 12 months. Other G1 GU toxicities experienced by >10% of patients were urinary tract obstruction, tract pain, and urgency. These symptoms also peaked in incidence at 3 months. G2 GU toxicities were uncommon and experienced in a maximum of 2 patients within each arm at any time point. Over 30% of patients had G1 flatulence at baseline, and this remained the most frequently occurring G1 GI toxicity throughout the study, peaking at 12 months (21.4% and 25.6% in Arm A and B, respectively). Other GI toxicities experienced by more than 10% of patients were GI pain, proctitis, and rectal mucositis, most of which demonstrated a peak incidence at 3 or 9 months. G2 GI toxicities were uncommon except for G2 flatulence. No significant difference was found in CTCAE, IPSS, IIEF, FACT-P, and QOL scores between the arms. Median prostate-specific antigen (PSA) follow-up was 5 years. Seven patients had treatment failure in each arm. Disease Free Survival (DFS) was 93.3% and 90.7% at 5 years in Arm A and B, respectively, with median failure time of 60 and 48 months in Arm A and B, respectively. There were no statistically significant differences between arms.

The sequencing of HDR-BT and EBRT did not affect the incidence of G3 or G4 toxicities, and no significant differences were seen in other patient-reported outcomes. Treatment was well tolerated with maintained QOL scores. Treatment failure was low in both arms in a high-risk cohort; however, a larger study with longer follow-up is underway to establish whether the difference in median time to failure between the 2 arms is a signal of superiority.