Low Rates of in-Field Recurrence with Regional Nodal Salvage Radiation and Temporary Androgen Deprivation for Pelvic and/or Para-Aortic Prostate Cancer Nodal Recurrences Detected By C11 Choline PET/CT Following Primary Therapy

Abstract

C11 choline PET/CT enables localization of prostate cancer recurrences in patients (pts) with rising prostate-specific antigen (PSA), yet the role of salvage external beam radiotherapy (sEBRT) for isolated lymph node recurrences detected by such imaging remains undefined. We report our clinical outcomes of sEBRT to sub-diaphragmatic lymph node recurrences combined with extended duration androgen deprivation therapy (ADT). Pts who received sEBRT to lymph node recurrences localized with C11 choline PET/CT between 2012 and 2017 were eligible for study. Pts with choline-avid lymph nodes beyond the retroperitoneum, bone metastases, or castrate-resistance were excluded. Clinical outcomes were analyzed separately from time of sEBRT completion, ADT completion, and testosterone recovery > 50 ng/dL using Kaplan-Meier and competing risk methods. Biochemical recurrence was defined as a PSA level >0.2 ng/mL for pts with prior radical prostatectomy (RP) and >2.0 ng/mL for those who received prior definitive EBRT or brachytherapy (BT). Post-sEBRT radiographic recurrence was analyzed with death as a competing risk. In-field recurrences were defined as those occurring within the 50% sEBRT prescription isovolume. 97 pts were identified with median age of 69 years (range 48-84) and median follow up of 3 years. All pts had received either RP (82), EBRT (8), or BT (7), with a rising PSA that prompted choline PET/CT which identified recurrent pelvic and/or para-aortic lymph nodes. sEBRT was delivered with ADT of 12 to 24 month intended duration. Typical sEBRT fields boosted involved nodes to 56.25 Gy in 25 fractions while simultaneously treating adjacent elective regional nodes to 45 Gy. In the 21 post-RP pts without prior salvage RT, the prostatic fossa was treated concurrently (dose range 64.8-72 Gy). At 4 years, overall survival was 98%. Biochemical recurrence rates at 2 and 4 years were 21% (95% CI 13-29%) and 53% (95% CI 35-65%), respectively. Rates of any radiographic recurrence at 2 and 4 years were 7% (95% CI 4-15%) and 25% (95% CI 16-40%): In-field recurrences were 1% (95% CI 0.2-7%) and 6% (95% CI 2-18%), and out-of-field recurrences were 6% (95% CI 3-14%) and 24% (95% CI 15-39%). At last follow up, 47 pts (48%) remained alive without radiographic recurrence or biochemical failure, and, of those, 28 pts (29% of total) were off ADT with testosterone ≥ 50 ng/dL. Choline PET/CT-guided sEBRT incorporating pelvic and para-aortic nodal recurrences and adjacent elective sites with extended duration ADT is associated with low rates of in-field recurrence. Out-of-field distant metastases represent the predominant pattern of failure, supporting the use of ADT-based strategies. Prospective clinical trials evaluating this approach are warranted.