Dosimetric and Hematologic Implications of Prostate-Only Versus Whole Pelvic Radiotherapy: Results of the Multicentric Phase 3 PROPER Study

Objectives: The aim is to evaluate the incidental dose to the lymphatic regions in prostate-only radiotherapy (PORT) and to compare hematological outcome between PORT and whole pelvic radiotherapy (WPRT) in node-positive prostate cancer (pN1 PCa), in the era of modern radiotherapy techniques. Methods: We performed a prospective phase 3 trial in which a total of 64 pN1 PCa patients were randomized between PORT (ARM A) and WPRT (ARM B) delivered with volumetric-modulated arc therapy (VMAT). The lymph node (LN) regions were delineated separately and differences between groups were calculated using Welch t-tests. Hematological toxicity was scored according to common terminology criteria for adverse events (CTCAE) version 4.03. To evaluate differences in the evolution of red blood cell (RBC), white blood cell (WBC), and platelet count over time between PORT and WPRT, 3 linear mixed models with a random intercept for the patient was fit with model terms randomization group, study time point, and the interaction between both categorical predictors. Results: Except for dose to the obturator region, the incidental dose to the surrounding LN areas was low in ARM A. None of the patients developed severe hematological toxicity. The change in RBC from time point pre-external beam radiotherapy (EBRT) to month 3 and for WBC from time point pre-EBRT to months 3 and 12 was significantly different with ARM B showing a larger decrease. Conclusion: The incidental dose to the lymphatic areas becomes neglectable when PORT is delivered with VMAT. Hematological toxicity is very low after WPRT with VMAT and when bone marrow constraints are used for planning, although WPRT causes a decrease in RBC and WBC count over time.