Radiobiological analysis of preliminary results of a phase II study of pelvic hypofractionated and accelerated radiotherapy for high-risk prostate cancer patients.

Purpose: Conventionally fractionated radiotherapy (CRT) is widely applied for the treatment of high-risk prostate cancer. Pelvic node irradiation improves control of the disease. Although the therapeutic guidelines support the use of hypofractionated and accelerated radiotherapy (HypoAR), this is addressed to prostate and seminal vesicles. At the same time, the safety and efficacy of HypoAR for pelvic node irradiation remain obscure. Material and Methods: In a phase II study, we evaluated the feasibility of pelvic HypoAR in 22 high-risk prostate cancer patients. The RT scheme delivers 14 consecutive fractions of 3.67 Gy (total 51.38 Gy) to the prostate, 3.5 Gy (total 49 Gy) to the seminal vesicles, and 2.7 Gy (total 37.8 Gy) to the lymph nodes, using image-guided volumetric modulated arc therapy. A comparative radiobiological analysis of dose-volume histogram is performed (HypoAR vs. hypothetical equivalent CRT regimens, without and with time correction).

Results: Our clinical experience shows impressively low early and short-term late toxicities, without any grade III events, within a median follow-up of 30 months. Only one biochemical relapse was recorded 30 months after irradiation. In radiobiological analysis, considering an α/β-value of 4 Gy and a λ-value of 0.2 Gy/day for late effects, all comparisons predicted significantly lower toxicity for the HypoAR regimen (p < 0.05). For early toxicities (α/β = 10 Gy), a λ-value lower than 0.4 Gy/day favors the HypoAR regimen, which is along with the clinical results.

Conclusion: Radiobiological analysis favors HypoAR as a safe and effective regimen for high-risk prostate cancer patients, which is confirmed in the current phase II clinical study.