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A Phase III Randomized Trial of MRI-Mapped, Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial

Amber Orman, MD; Alan Pollack, MD, PhD; Kelin Wang, PhD; Radka Stoyanova, PhD; Elizabeth Bossart, PhD; Deukwoo Kwon, PhD; Matthew Abramowitz, MD
Published: Sunday, Jun 28, 2015
Amber Orman, MD

About the lead author:
Amber Orman, MD
Department of Radiation Oncology
Miller School of Medicine
University of Miami

The Reviewer’s Viewpoint

Jonathan D. Tward, MD, PhD
Jonathan D. Tward, MD, PhD
Department of
Radiation Oncology
Huntsman Cancer Hospital
University of Utah

Why is this article contemporary?
Conventionally fractionated dose escalation above 78 Gy for intact prostate cancer has been shown to improve failure- free survival. Previously occult prostatic fossa recurrences can now occasionally be visualized using advanced imaging methods such as MRI. As the disease is no longer “microscopic,” it stands to reason that dose escalation to the recurrent tumor may improve failure-free survival in the salvage setting as well.

In the current study, the authors report on the feasibility and acute toxicity of the first 14 patients enrolled on a trial randomizing subjects to either standard 68 Gy radiotherapy to the fossa, or the same plus a simultaneous integrated boost of 76.5 Gy at 2.25 Gy/fx (EQD2= 82 Gy, alpha/ beta assumption 1.5).

In this initial report, the authors showed the dosimetric feasibility via DVH parameters of the approach and that there was clinically no discernible acute toxicity difference between the standard arm and the dose-escalated arm. The trial continues to accrue and we await reports on late toxicity as well as impact on their primary endpoint of biochemical failure-free survival. If the authors ultimately show improved bRFS and similar late toxicity, then dose escalation to visualized fossa lesions should become a new care standard.

Abstract

Objective

MAPS is the first phase III randomized trial of MRI-mapped, dose-escalated salvage radiotherapy. In this planned feasibility analysis, we ensure dosimetric adequacy of the protocol as it relates to acute toxicity.

Materials and Methods:

Two intensity modulated radiotherapy plans were generated for each patient. In the standard fraction radiotherapy arm, 68 Gy in 34 fractions was prescribed to ≥95% of the planning target volume. In the simultaneous incorporated hypofractionated boost (SIHB) arm, an additional 2.25 Gy daily SIHB was prescribed to the gross tumor volume (GTV). The trial stipulates that ≤35% and ≤55% of the rectum should receive ≥65 Gy and ≥40 Gy, respectively, and ≤50% and ≤70% of the bladder minus the clinical target volume (B-CTV) should receive ≥65 Gy and ≥40 Gy, respectively. Acute toxicities were recorded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0).

Results
In all plans, ≥95% of the planning target volume and GTV received the prescribed dose. Dosimetric constraints were achieved for all organs at risk except B-CTV. The highest toxicity recorded was grade 2 gastrointestinal toxicity: 1 episode per arm.

Conclusions:

Dose escalation is achievable with expected variations in cases with small bladders. There was no observed increase in acute toxicity.


Introduction

Radical prostatectomy (RP) cures the majority of patients with localized prostate cancer. However, within 10 years of diagnosis as many as one-third will develop recurrent disease.1,2 In the setting of localized recurrence, salvage radiotherapy to the prostate bed is the standard treatment. However, long-term salvage rates remain suboptimal, possibly due to poor patient selection.3,4

Ideally, only those with disease isolated to the prostate bed would receive treatment. Dynamic contrast-enhanced (DCE) MRI has been shown to reveal residual or recurrent disease with specificities of at least 80%, and sensitivities ranging from 67% to 97%.5 This is an improvement over transrectal ultrasound and conventional imaging,6 provides objective evidence for treatment, and identifies a target for dose escalation.

Compared with definitive radiotherapy, salvage doses are lower due to the assumption of only microscopic disease and toxicity limits associated with treating the bladder neck.

However, dose escalation may show benefit,7,8 and radiobiological modeling predicts that PSA control rates will increase along with increasing doses.8,9 In terms of toxicity, salvage IMRT up to 76 Gy results in <1% grade 3 GI toxicity, and 3% grade 3 GU toxicity at 5 years.10


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