Phase I/II Study of Extreme Hypofractionated Stereotactic Body Radiation Therapy Boost to Prostate for Locally Advanced, Node-Positive and Oligometastatic Cancer.

Kushal Narang,Deepak Gupta,Susovan Banerjee,Saumyaranjan Mishra,K Venkatesan,Shyam Bisht,Mohit Kadian,Tejinder Kataria

doi:10.7759/cureus.11751

Abstract

Introduction: Stereotactic body radiation therapy (SBRT) is increasingly being utilized to deliver escalated radiation doses for improving outcomes in various malignancies. We analyzed our cohort of locally advanced, node-positive, and bone oligometastatic prostate cancer patients, that were treated with a combination of pelvic RT using conventional fractionation (CF) and SBRT boost to prostate using extreme hypofractionation (EH), along with hormone therapy (HT).Materials and Methods: Outcomes of 44 prospectively treated patients were analyzed. Volumetric modulated arc therapy (VMAT) was utilized to deliver a dose of 45 Gy to pelvic nodal region, 50 Gy to prostate, and 54-56 Gy to gross nodes in 25 fractions. EH boost 18 Gy in three fractions was delivered to the prostate using CyberKnife (Accuray, Sunnyvale, CA, USA) SBRT. Bone oligometastasis, if any, were treated to a dose of 16 Gy in two fractions, delivered on weekends. Serum prostate-specific antigen (PSA), multi-parametric magnetic resonance imaging (MRI) of pelvis, and prostate-specific membrane antigen-positron emission tomography (PSMA-PET) were used for response assessment during follow-up. HT was given as per standard guidelines.Results: There were 33 (75%) locally advanced, nine (20.5%) node-positive, and two (4.5%) oligometastatic cases. At a median follow-up of 63.5 months, the five-year progression-free survival (PFS) was 88.2%, biochemical PFS (bPFS) was 91.4% and overall survival (OS) was 96.9%. Grade III or greater acute genitourinary and gastrointestinal toxicity was 2.3% each, and late toxicity was 4.5% and 0%, respectively.Conclusion: Excellent five-year outcomes can be attained even for locally advanced, node-positive and bone oligometastatic prostate cancer, by means of dose-escalation using EH-SBRT boost to the prostate.

Highlights

Stereotactic body radiation therapy (SBRT) is increasingly being utilized to deliver escalated radiation doses for improving outcomes in various malignancies
Prostate cancer (PC) has an alpha/beta (α/β) value of around 1.5, which is lower than that of nearby critical structures like the bladder and rectum. This means that irradiating with doses per fraction greater than conventional fractionation (CF) would deliver a greater biologically equivalent dose (BED) to the prostate, without significantly increasing late normal tissue toxicity
Bladder and rectum (α/β = 3) received a maximum BED of 137.3 Gy, with an EQD2 of 82.4 Gy, and bowel (α/β = 3) received maximum BED of 72 Gy (EQD2 43.2 Gy). In their meta-analysis of conventional and hypofractionated schedules [18], demonstrated that BED of around 200 Gy to prostate is important for attaining favourable long-term control rates, and restricting critical structure BED around 133 Gy helps limit normal tissue toxicity. While this is easier for capsule-confined localized PC, dose-escalation for more advanced disease extending into neurovascular bundle or seminal vesicles, results in potentially toxic doses being delivered to bladder and rectum

Summary

Introduction

Stereotactic body radiation therapy (SBRT) is increasingly being utilized to deliver escalated radiation doses for improving outcomes in various malignancies. We analyzed our cohort of locally advanced, node-positive, and bone oligometastatic prostate cancer patients, that were treated with a combination of pelvic RT using conventional fractionation (CF) and SBRT boost to prostate using extreme hypofractionation (EH), along with hormone therapy (HT). Multiple phase two and phase three studies employing extreme hypofractionation (EH; ≥5 Gy per fraction) have reported excellent control rates with acceptable bladder and rectal toxicity Most of these studies have evaluated low-intermediate risk, localized PC [4], data for EH for high-risk, localized and advanced PC is rapidly accumulating [5,6,7,8,9,10,11,12]. We hereby report the five-year outcomes for this cohort

Methods

Results

Discussion

Conclusion