Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial

Alessandro Magli,Giulia Bravo,Marco Trovò,Eugenia Moretti,Fabrizio Tonetto,Claudio Foti,Margherita Polsinelli,Gioacchino De Giorgi,Annarita Tullio,Paolo Scalchi,Agnese Prisco,Mauro Urpis,Margherita Crespi,Gianluca Giannarini

doi:10.1038/s41391-018-0034-0

Abstract

ObjectiveThe approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance.Materials and methodsIn this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated - Intensity Modulated Radiotherapy) were delivered between 2009 and 2012. All patients enrolled (41) received in 25 fractions a total dose of 67.5 Gy (2.7 Gy/fraction) to the prostatic volume, 56.25 Gy (2.25 Gy/fraction) to the seminal vescicles, and 50 Gy (2.0 Gy/fraction) to the pelvic lymph nodes (LN) chains with concurrent androgen deprivation therapy (ADT). The image-guided radiotherapy (IGRT) procedure was performed using three gold seeds. RTOG late gastrointestinal and genitourinary toxicities and 6-year biochemical relapse-free survival (BRFS) were assessed in combination of their statistical correlation with clinical factors and dosimetric parameters.ResultsRate of late genitourinary toxicity grade 2 was 9.8%, while rates of late gastrointestinal toxicity were 14.6% and 2.4%, for grade 1 and 2, respectively. Diabetes and maximum doses to rectum appeared to be statistically relevant risk factors for late rectal toxicity. Five-year BRFS was 95.1%.ConclusionsIn our study, we observed positive results in terms of toxicity and good efficacy in a cohort of high-risk prostate cancer patients treated with a multimodality therapy approach comprising hypofractionation, irradiation of pelvic nodes (common iliac nodes included), and concurrent ADT. These favorable results may merit further investigation in a phase III randomized trial to confirm that whole pelvic radiation therapy (WPRT) combined with moderate hypofractionation and ADT could be performed safely and effectively.

Highlights

Localized high-risk prostate cancer (PCa) is related to a substantial disease recurrence after the33100 Udine, Italy 4 Department of Urology, University Hospital of Udine, ASUIUD - piazzale S.M della Misericordia 15, 33100 Udine, Italy 5 Department of Radiation Oncology, IOV-IRCCS Padova, ViaGattamelata, 64, 35128 Padova, Italy 6 Department of Medical Area, University of Udine, ASUIUD - piazzale S.M della Misericordia 15, 33100 Udine, Italy administration of local treatment with radical intent, regarding more than 50% of patients within 10 years post treatment [1, 2]
According to NCCN and EAU guidelines recommendations, the standard of care is represented by external beam radiation therapy (EBRT) associated with long-term androgen deprivation therapy (ADT)
Roach et al [3] reported the results of the Radiation Therapy Oncology Group 94-13 randomized trial, which proven significantly better progression-free survival for high-risk PCa treated with whole pelvic radiation therapy (WPRT) compared with prostate-only radiation therapy (PORT)

Summary

Introduction

Localized high-risk prostate cancer (PCa) is related to a substantial disease recurrence after the. 33100 Udine, Italy 4 Department of Urology, University Hospital of Udine, ASUIUD - piazzale S.M della Misericordia 15, 33100 Udine, Italy 5 Department of Radiation Oncology, IOV-IRCCS Padova, Via. Gattamelata, 64, 35128 Padova, Italy 6 Department of Medical Area, University of Udine, ASUIUD - piazzale S.M della Misericordia 15, 33100 Udine, Italy administration of local treatment with radical intent, regarding more than 50% of patients within 10 years post treatment [1, 2]. Roach et al [3] reported the results of the Radiation Therapy Oncology Group 94-13 randomized trial, which proven significantly better progression-free survival for high-risk PCa treated with whole pelvic radiation therapy (WPRT) compared with prostate-only radiation therapy (PORT). Cute gastrointestinal (GI) and genitourinary (GU) complications were most commonly occurred in patients treated with WPRT than in those receiving PORT [5, 6]

Methods

Results

Conclusion