Radiation-Associated Lymphopenia in Advanced Prostate Cancer Treated with Contemporary Radiation Techniques.

Abstract

Lymphocytes play a critical role in the immune system as primary effector cells for cancer control, often depleted by external beam radiation therapy (EBRT). Radiation-associated lymphopenia (RAL) has been shown to be a poor prognostic factor in the management of multiple solid tumors. We hypothesize RAL is similarly observed in advanced prostate cancer (PC) RT with contemporary techniques. We identified patients with advanced PC (high-risk or clinical/pathologic node-positive) receiving EBRT including lymph node/prostatic lesion boost on a prospective collection protocol for whom 1 baseline and ≥2 subsequent complete blood count (CBC) with differential samples were available, collected at RT end, 3-, 6-, and 12-months post-RT. Clinicopathological characteristics were retrieved from chart review. Common Terminology Criteria for Adverse Events (CTCAE)v5 was used to grade absolute lymphocyte count (ALC); RAL was defined as CTCAEv5 grade ≥2. As these patients received pelvic nodal irradiation, they were pooled with low/intermediate-risk PC cohort treated with high dose-rate (HDR) brachytherapy or prostate alone EBRT with similar CBC timepoints for univariable analysis to understand RT field size effect on RAL. Between 2019 and 2022, among 17 patients in the low/intermediate-risk PC cohort, 6 patients had grade ≥2 lymphopenia. Among 25 patients in the advanced PC cohort, all received androgen deprivation therapy (ADT), 6 received lymph node boost, and 5 received prostatic lesion boost. At RT end, leukopenia was prominently observed (median nadir count 75.1% of baseline), with ALC as major driver (median nadir count 27.3% of baseline). Grade ≥2 lymphopenia was observed in 76% of patients (n = 19) Of 19 advanced PC patients who reached 6 months post-RT follow-up, median ALC was 53.0% of baseline, and Grade ≥2 lymphopenia remained in 37% (n = 7) of patients. Of 8 advanced PC patients who reached 12 months post-RT follow-up, median ALC was 55.6% of baseline. When evaluating whether RT dose or field size contributed to lower nadir ALC counts, combining the low/intermediate-risk and advanced PC cohorts (n = 42), univariable analysis demonstrated Gleason grade group (p = 0.009), RT field size (p = 0.020), ADT use (p = 0.020), baseline ALC (p = 0.037), and baseline hemoglobin (p = 0.009) were independent predictors of Grade ≥2 lymphopenia. Age, prostatic lesion/lymph node boost, and equivalent dose in 2 Gy/fraction (EQD2) were nonsignificant. Grade ≥2 RAL was observed in patients with advanced PC at end of RT, irrespective of age, RT boost, or EQD2. Lymphocyte recovery from baseline can be prolonged even at 12 months post-RT. Ongoing analyses include expanding data with additional serial CBC, increasing cohort size, and integrating effect of additional systemic therapies. RAL has downstream implications for future chemotherapy/radiopharmaceuticals.