Radiation-related Lymphopenia After Pelvic Nodal Irradiation for Prostate Cancer

Purpose: Given the uncertainty with regard to the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether patients with prostate cancer who are treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL).

Methods And Materials: The electronic charts of 886 consecutive patients treated with radiation therapy for prostate cancer between 2006 and 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts within 1 year before and 3 to 24 months after the start of radiation therapy. Lymphopenia was the primary outcome, and overall survival and biochemical progression-free survival were secondary outcomes.

Results: Thirty-six patients with and 95 patients without PNI qualified for inclusion. In the PNI cohort, 61.1% of patients developed RRL (median follow-up total lymphocyte count < 1000 cells/μL) versus 26.3% of non-PNI patients ( < .001). On univariate analysis, initial prostate-specific antigen level, baseline lymphopenia, treatment modality, PNI status, increased planned target volume, and androgen deprivation therapy administration were all significant predictors of RRL ( < .05). On multivariate analysis, PNI status was a significant predictor of RRL (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.22-9.61;  < .001), as were initial prostate-specific antigen values (HR, 1.05; 95% CI, 1.00-1.11;  = .006) and baseline lymphopenia (HR, 8.32; 95% CI, 2.19-31.6;  = .007). RRL was not predictive for biochemical progression-free survival, distant metastasis, or overall survival on multivariate analysis, but the number of events was likely insufficient for these analyses.

Conclusions: The higher risk of RRL among patients with PNI comports with other papers that show that increased treatment volumes are associated with higher rates of RRL. Mounting evidence for the adverse effects of RRL on clinical outcomes supports the significance of our findings and suggests that further studies are needed on RRL as a potential harm of PNI that may affect the interpretation of results from clinical trials of PNI.