Association between lymph node burden and overall survival among patients treated with adjuvant radiation therapy following radical prostatectomy
Syed N. Rahman, MD1, Thomas F. Monaghan, MD2, Soum Lokeshwar, MD1, Tashzna Jones, MD1, Andrew G. Winer, MD2, Michael S. Leapman, MD1.
1Yale School of Medicine, New Haven, CT, USA, 2SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
BACKGROUND: Although there is increasing evidence to support the use of adjuvant radiation therapy among patients with lymph-node positive prostate cancer after radical prostatectomy (RP), however it is unclear whether benefits persist for patients with high burdens of metastatic disease. We aimed to evaluate the association between the number of positive lymph nodes identified at the time of radical prostatectomy and lymph node dissection and overall survival after adjuvant androgen deprivation therapy (ADT) and radiation therapy (EBRT) versus ADT alone. METHODS: We identified patients with lymph node positive (pT2-4N1M0) prostate cancer treated with RP in the National Cancer Database (2004-2017). The primary study objective was to compare overall survival among patients who received adjuvant ADT alone versus ADT+EBRT across numbers of positive lymph nodes identified (<3 versus ≥3). In addition, we compared survival across numbers of positive lymph nodes identified among patients receiving adjuvant versus salvage (>6 month) radiation. We compared overall survival (OS) using multivariable Cox proportional hazards models adjusted for clinical and pathological characteristics including the number of total lymph nodes removed during PLND. RESULTS: We identified 6,099 patients who met inclusion criteria. After RP, 3267 patients (53.6%) received ADT alone and 2832 (46.4%) received ADT+EBRT. Patients treated with adjuvant ADT+EBRT were younger (60.9 vs 62.4 years), and a higher percentage of positive surgical margins (64.9% vs. 53.2%). However, patients receiving ADT alone had a higher mean PSA 22.4 vs 21.2 ng/dl). Cox proportional hazards regression revealed that ADT+EBRT versus ADT alone was associated with improved OS (HR=0.65 [0.53-0.80] p<0.001) in the total cohort. This persisted at among patients with <3 positive lymph nodes identified (HR=0.61[0.48-0.79] p<0.001). However, among patients with >3 positive lymph nodes identified, ADT+EBRT was not associated with improved survival compared with ADT alone (HR=0.65 [0.52-1.09] p=0.13). Receipt of salvage RT among patients with >3 positive lymph nodes treated with salvage radiation were associated with worse OS compared with adjuvant radiation (HR=2.08 [1.08-3.85] p=0.02). Salvage radiation was not associated with worse OS in those with <3 positive lymph nodes (HR=0.79[0.49-1.27] p=0.33).
CONCLUSIONS: Although adjuvant ADT+EBRT was associated with improved survival among patients with node-positive prostate cancer at the time of radical prostatectomy, we did not identify a survival benefit among patients with greater than three lymph nodes identified. Salvage radiation may be an alternative to adjuvant radiation below 3 positive lymph nodes identified. 
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