Once‐a‐week or every‐other‐day urethra‐sparing prostate cancer stereotactic body radiotherapy, a randomized phase II trial: 18 months follow‐up results

Abstract

Background:To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra-sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa). Methods: Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months. Results: Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ-PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate. Conclusions: At 18 months, urethra-sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW). K E Y W O R D Soverall treatment time, prostate cancer, quality of life, stereotactic body radiotherapy, urethra sparing 3098 | ZILLI et aL.

Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review

“…Patients in the experimental arm were treated with 7 × 6.1 Gy to the prostate without the seminal vesicles, whereby roughly ¾ of patients were treated with 3D-conformal RT (3DCRT). Zilli and colleagues conducted a phase II trial investigating urethra-sparing SBRT with treatment once a week vs. every other day with a prescription dose of 5 × 7.25 Gy to the prostate ± the seminal vesicles [ 58 ]. King et al [ 29 ] reported on pooled phase II data of a multi-institutional consortium.…”

“…In the phase II trial conducted by Zilli and colleagues, a 6-month LHRHa treatment (2 months neoadjuvant) was mandatory in all patients with HR features [ 58 ]. In the US multi-institutional phase II series, 38% of the HR PCA patients underwent short-course neoadjuvant and concurrent ADT for a median duration of 4 months [ 29 ].…”

“…Zilli et al did also not specify BCR of their HR patients [ 58 ]. King and colleagues reported a similar disease control probability for their HR PCA patients with a bPFS of 81.2% after 5 years in their pooled analysis of phase II data [ 29 ].…”

Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial

“…These are likely driven by radiation dose delivered to critical adjacent normal tissue. Aggressive urethral sparing in CT-guided SBRT has shown a considerable reduction in acute GU toxicity demonstrated by Zilli et al [ 35 ]; however, certain key features of this practice such as routine use of a Foley catheter and endorectal balloon may limit the widespread adoption. The dose in that study (36.25Gy in 5 fractions) is also lower than in the present study.…”

Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference

“…Urethra sparing is performed in SBRT and brachytherapy, since higher urethral doses are associated with higher GU toxicities (59,60). The recently published toxicity reports of the hypoFlame trial suggest that prioritization of OAR constraints yields acceptable toxicities for focal dose escalation using SBRT.…”