Multiparametric MRI Guided Salvage Low Dose Rate Brachytherapy for Locally Recurrent Prostate Cancer - The 15 Year Richmond Experience

Salvage permanent low dose rate brachytherapy (LDR-BT) has long been offered at our institution with mpMRI guidance for patients who develop locally recurrent prostate cancer following external beam radiotherapy (EBRT) or prior LDR-BT. It was hypothesized that this approach is associated with a delay and/or avoidance of androgen deprivation therapy (ADT) in the majority of patients, and might be associated with only rare occurrences of severe late toxicities. As part of a quality improvement project, we reviewed the patient, tumor, and treatment characteristics for all patients who underwent a salvage LDR-BT between 2001-2015 at our institution. All patients had undergone a restaging mpMRI scan with T2-weighted imaging, diffusion weighted imaging, and dynamic contrast enhancement with or without spectroscopy (1.5-Tesla with endorectal coil or 3-Tesla with transabdominal phase array coil). Concerning lesions were biopsied via mpMRI-guidance. Salvage LDR-BT plans were developed to encompass the suspicious regions on the mpMRI images and implanted under anesthesia with either I-125 or Pd-103. Post-implant dosimetry was available for all patients except for two who underwent salvage LDR-BT after prior LDR-BT. Genitourinary and gastrointestinal toxicities were retrospectively coded using CTCAE 4.0. The Kaplan-Meier method was used to estimate the time to re-recurrence, which was defined as the post-LDR-BT PSA nadir + 2 ng/mL, or initiation of ADT. A total of 39 patients were identified with a median follow-up time of 55 months. The median age at relapse was 72 (range: 52-91). The initial course of radiotherapy had been EBRT, LDR-BT, or a combination in 77%, 15%, and 8%, respectively. The median time from initial radiotherapy to salvage LDR-BT was 80 months (range: 22 - 156 months). The median rPSA and rPSA doubling times were 5.8 ng/mL (range: 1.2-26.4 ng/mL) and 18.1 months (range: 1.9-36.3 months), respectively. Restaging biopsies with mpMRI guidance were performed in 33 patients and identified Gleason’s score (GS) 8-10, GS 7, GS ≤6, PIN and benign changes in 39%, 33%, 6%, 12%, and 9%. Following salvage LDR-BT, the PSA response rate was 100%. The K-M adjusted freedom from re-recurrence was 46% at 55 months. All failures occurred between 3-44 months with a median time to failure of 21.9 months. Four patients developed grade 3 toxicities (incontinence = 2; rectal ulcer = 2). There were no grade 4-5 toxicities. Two patients developed metastasis at 55 and 98 months. Among 13 deceased patients, 1 died as a result of relapse, 5 with recurrence but not from relapse, and 7 died without relapse. Nearly half of all patients who underwent mpMRI-guided salvage LDR-BT had long-term PSA control and avoided ADT. This likely improves patient health, but its impact on metastases, prostate cancer mortality, and overall survival cannot be determined from this retrospective study. Improved ultrasound imaging, planning techniques, and the introduction of injectable rectal spacers over the study period have eliminated grade 3 toxicities. However, our experience provides a reminder that they are to always be discussed with patients whenever offering this treatment.