State of the Art and Future Challenges of Urethra-Sparing Stereotactic Body Radiotherapy for Prostate Cancer: A Systematic Review of Literature

The dose delivered to the urethra has long been known to be associated with the late onset of genitourinary (GU) toxicity and more specifically urethral strictures, especially after prostate cancer (PCa) brachytherapy (BT). More recently, the FLAME trial demonstrated a non-linear relationship between maximal doses delivered to the urethra and late onset of grade ≥2 GU toxicity, paving the way towards urethra-sparing radiotherapy in situations of dose-escalation to the prostate gland. With hypofractionation becoming a new standard for the treatment of localized disease, several urethra-sparing (US) techniques have been implemented for PCa stereotactic body radiotherapy (SBRT).

Based on the urethra sparing technique, two distinct categories can be identified: the “urethra-steering” SBRT (restriction of hotspots to the urethra) and the “urethra dose-reduction” SBRT (dose reduction to urethra below the prescribed dose).

The “urethra dose-reduction” strategy has been explored in a phase II multicenter randomized trial by Zilli et al., proposing a US-SBRT schedule with a total dose of 36.25Gy in 5 fractions to the whole prostate gland and a dose reduction on a 2-mm planning organ-at-risk volume (PRV) around the urethra performed either every-other-day (EOD) or once-a-week (QW). With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the incidence of CTCAE grade 2 GU toxicity was below 10% for both arms, respectively, corresponding to a 5-year grade 2 or greater GU toxicity-free survival of 75.9% and 76.1% for patients treated EOD versus QW, respectively (P = .945). This strategy, applied to a population mostly represented by low- to intermediate-risk PCa has demonstrated a 5-year biochemical relapse-free survival (bRFS) exceeding 90%.

The "urethra-steering” technique was preferred across trials when a simultaneous integrated boost (SIB) was performed within the prostate gland. Although long-term toxicity results are not yet published, urethra-steering with maximal urethral doses < 90Gy EQD2 was associated with rates of late grade 2 GU toxicity ranging between 12.1% and 14%, with no report of any grade 3 GU toxicity. No date few data are available with regards to oncological outcomes.

Although US-SBRT represents a promising technique for the mitigation of late GU toxicity after PCa radiotherapy, precise definition of urethra represents one of the major limitations to the implementation of this technique in clinical practice. As the urethra cannot be identified on planning computed tomography (CT), use of a urinary catheter can be considered despite its use has been associated with an increased rate of shifts in the organ position. Magnetic resonance imaging (MRI) has been increasingly implemented within trials as an alternative to determine urethral position, yet remains limited by inter-fractions anatomical changes. In this setting, magnetic resonance guided radiotherapy (MRgRT) could provide both benefits of adaptive radiotherapy and a precise delineation of the urethra at each session.

Written by: Jennifer Le Guevelou,¹Davide Giovanni Bosetti,²Francesco Castronovo,²Antonio Angrisani,²Renaud de Crevoisier,¹Thomas Zilli^2,3,4

Radiation Oncology, Center Eugène Marquis, Rennes, France
Department of Radiation Oncology, Oncology Institute of Southern Switzerland (IOSI), EOC, Bellinzona, Switzerland
Facoltà Di Scienze Biomediche, Università Della Svizzera Italiana (USI), Lugano, Switzerland
Faculty of Medicine, University of Geneva, Geneva, Switzerland

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