Efficacy and safety of bovhyaluronidase azoximer in patients undergoing transurethral resection of the prostate

Abstract

Introduction. Inflammation and fibrosis may have a significant role in pathogenesis of benign prostatic hyperplasia and associated lower urinary tract symptoms. Moreover, those factors may compromise the outcomes of surgical interventions for bladder outlet obstructions, such as transurethral resection of the prostate (TURP). Additional measures, such as administration of anti-fibrotic agents, may decrease the incidence of certain complications (e.g. bladder neck stenosis, urethral stricture) and improve overall outcomes of TURP. Bovhyaluronidase azoximer is an enzyme combined with high molecular mass copolymer which may inhibit surgery-related tissue remodeling and prevent excessive fibrosis.Materials and methods. Sixty-five patients undergoing monopolar TURP were enrolled in this prospective randomized open-label study. Patients in Group 1 (n = 34) received 5 intramuscular injections of bovhyaluronidase azoximer (3000 IU) on days 3, 6, 9, 12 and 15 after TURP in addition to standard therapy. Patients in Group 2 (n = 31) received conventional peri-operative therapy. All patients routinely underwent uroflowmetry and post-void residual volume measurement on follow-up 3 months after TURP. Incidence of fibrosis-associated complications was compared using Fisher’s exact test. Uroflowmetric parameters were compared using Mann-Whitney U-test.Results. One patient in Group 1 was excluded from the study due to mild allergic reaction after second injection of bovhyaluronidase azoximer. There were three cases of clinically significant fibrosis-associated complications in Group 2 which were confirmed on imaging (9.7 %). One case of stricture in bulbar urethra was later successfully managed with anastomotic urethroplasty, and two cases of bladder neck stenosis were managed with transurethral incision. No such complications were observed in Group 1 (0 %). However, the difference was not statistically significant (p = 0.1079). Otherwise, there were no adverse events in both groups. Median Qmax in Groups 1 and 2 was 24 ml/s and 22 ml/s, respectively (p = 0.08). Median Qave in Groups 1 and 2 was 15 ml/s and 9 ml/s, respectively (p <0.00001). Median of post-void residual volume in Groups 1 and 2 was 25 ml and 40 ml, respectively (p = 0.00438).Conclusion. This study was underpowered to demonstrate significant difference in incidence of fibrosis-related complications of TURP, though there was a trend towards lower risk in patients treated with bovhyaluronidase azoximer. There was also a statistically significant difference in Qave and post-void residual volume in favor of Group 1, which may demonstrate lower rates of subclinical fibrosis. Overall, treatment with bovhyaluronidase azoximer was safe. Robust studies with longer follow-up are required to confirm efficacy of bovhyaluronidase preparations in post-TURP setting.