Single Fraction HDR Brachytherapy for Prostate Cancer: SiFEPI Phase II Trial Results

Abstract

<h3>Purpose/Objective(s)</h3> To report the results of the <i>Single Fraction Early Prostate Irradiation</i> (SiFEPI) phase 2 prospective trial. <h3>Materials/Methods</h3> The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and low-intermediate (LIR) risk prostate cancers. After injection of 10 ml of macromolecular hyaluronic acid (rectal spacer), needles were implanted under endorectal ultrasound guidance. After post-implant CT scan, a single fraction of 20 Gy was delivered to the prostate taking into account the dose constraints for CTV and organs at risk (urethra, rectum, anus). Oncological outcome (biochemical (bRFS), local (lRFS), and metastatic (mRFS) relapses and disease-free (DFS), cause-specific (CSS) and overall (OS) survivals), toxicity profile (acute [d30, d90, d180] and late [> 6 months] genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities) were investigated as well as quality of life (QLQ-C30 and QLQ-PR25). <h3>Results</h3> From March 2014 to October 2017, 35 pts were enrolled. Among them, 33 were evaluable. With a median age of 66 y [46 - 79], 25 (76%) and 8 (24%) pts were LR and FIR respectively. Median MRI prostatic volume was 41 cc [19 - 84]. Median peak-urinary flow and post-void residual volume were 17 ml/s [8 - 25] and 19 cc [0 - 165] while 30 pts (91%) had an IIEF score between 16 and 25. Median CTV, D90% and V100% were 50 cc [29 - 92], 106% [104 - 109], and 98% [96 - 99] respectively. With a MFU of 72.8 months [64 - 86], 6y-bRFS, lRFS and mRFS were 62% [45 - 85], 61% [44 - 85] and 93% [85 - 100] respectively while 6y-DFS, CSS and OS were 54% [37 - 77], 100% and 89% [77 - 100]. Acute GU, GI and S toxicities were observed in 27 pts (82%; 36 G1 & 8 G2), 5 pts (15%; 7 G1 & 3 G2) and 5 pts (15%; 3 G1 & 2 G2) respectively and no acute G3 toxicity was observed. Late GU, GI and S toxicities were observed in 11 pts (33%; 18 G1), 4 pts (12%; 4 G1) and 7 pts (21%; 1 G1, 5 G2 & 1 G3) respectively. QLQ-C30 and QLQ-PR25 will be reported later. Biochemical relapse (BR) was observed in 11 pts (33%; 7 LR & 4 FIR) with a median time interval between HDB and BR of 51 months [24 – 69]. Among them, 9 pts (82%) presented a histologically proven isolated local recurrence and underwent salvage prostate re-irradiation delivering a median dose of 78 Gy [73 – 78] (2 Gy/f). With a MFU from salvage EBRT of 27 months [3 – 59], 2^nd bRFS rate was 100%. One pt presented a G3 GU toxicity (hematuria) while no G≥3 GI complication was observed. <h3>Conclusion</h3> Long-term results of the SiFEPI phase 2 prospective trial showed that a single fraction of 20 Gy (HDB) leads to a sub-optimal biochemical control for LR and LIR prostate cancers. The reported oncological outcome is in line with the previous series of HDB single fraction protocols. However, late GU and GI toxicity profile is encouraging (especially compared to iodine implant series), leading to consideration of HDB as a safe irradiation technique. Salvage EBRT appears feasible with an acceptable risk of complications.