Hematological toxicity and bone marrow dose-volume effects in chemotherapy-naive patients treated with whole pelvic and para-aortic lymph node radiotherapy for pN1 prostate cancer

Abstract Purpose Whole pelvic radiotherapy (WPRT) combined with androgen-deprivation therapy (ADT) improves prostate cancer-specific survival in pN1 prostate cancer (PCa). Elective para-aortic radiotherapy (PART) may further improve clinical outcomes and is under investigation in the PART study (NCT NCT03079323). This study investigates the effect of WPRT plus PART on hematological toxicity (HemT). Materials and Methods HemT and bone marrow (BM) dose-volume relationships were analyzed in the first 75 PART patients enrolled in University Hospitals Leuven, all receiving 24 months of ADT or antiandrogen therapy. Hematological changes were assessed longitudinally. Associations were analyzed using linear models for repeated measures, with False Discovery Rate (FDR) correction. Results At 57-months median follow up (median age 66 years), no HemT caused treatment interruption. All blood parameters declined significantly after RT (all p < 0.01 at 1, 3, 6 and 24 months). Grade 4 toxicity was limited to lymphopenia (acute 7%, late 1%), grade 3 leukopenia occurred in 1% acutely and late. No grade 3-4 anemia or grade 2-4 thrombocytopenia was seen. BM dosimetric analysis showed that larger low dose volumes (V3, V5, and V10) in the lower pelvis, whole pelvis (WP), and WP plus retroperitoneal region were significant associated with greater late absolute lymphocyte count (ALC) decline. Every 100cm³ increase in absolute volume correlated with a late ALC decrease of -0.04 to -0.08 × 10⁹ /L (all FDR p ≤ 0.01). Conclusions Extended-field RT is clinically well tolerated in chemotherapy-naive pN1 PCa patients, with no toxicity-related treatment interruptions and <2% incidence of Grade ≥ 3 hematological events. However, persistent lymphopenia was observed. Dose-dependent association between low-dose BM irradiation (V3-V10) and late ALC decline supports further research into BM-sparing techniques to reduce long-term toxicity.